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Background and aims Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic painis subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state = pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats. Methods Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400 μg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR. Results Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls. Conclusions In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. Implications Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.

Objective This study examined the altered patterns of functional connectivity in task-positive resting state networks in failed back surgery syndrome (FBSS) patients compared to healthy controls using functional magnetic resonance imaging (fMRI). This work stems from a previous study in which alterations in the task-negative default mode network were investigated. Design Participants underwent a 7-minute resting state fMRI scan in which they lay still, with eyes closed, in the absence of a task. Setting Scanning took place at the National Research Council’s 3 Tesla MRI magnet in Winnipeg, Canada. Subjects Fourteen patients with FBSS and age- and gender-matched controls participated in this study. Three patients were removed from the analyses due to image artefact ( n = 1) and effective pain treatment ( n = 2). Eleven patients (5 female, mean age 52.7 years) and their matched controls were included in the final analyses. Methods Resting state fMRI data were analyzed using an independent component analysis, yielding three resting state networks of interest: the salience network (SN), involved in detection of external stimuli, central executive network (CEN), involved in cognitions, and sensorimotor network (SeN), involved in sensory and motor integration. Analysis of Variance contrasts were performed for each network, comparing functional connectivity differences between FBSS patients and healthy controls. Results Alterations were observed in all three resting state networks, primarily relating to pain and its processing in the FBSS group. Specifically, compared to healthy controls, FBSS patients demonstrated increased functional connectivity in the anterior cingulate cortex within the SN, medial frontal gyrus in the CEN, and precentral gyrus within the SeN. FBSS patients also demonstrated decreased functional connectivity in the medial frontal gyrus in the SeN compared to healthy controls. Interestingly, we also observed internetwork functional connectivity in the SN and SeN. Conclusions FBSS is associated with altered patterns of functional connectivity in the SN, CEN, and SeN. Taken together with our previous work, this reveals that a chronic pain condition can have a dramatic effect on the connectivity of multiple resting state networks. Implications These data suggest that a chronic pain condition—FBSS—is associated with disruptions to networks of functional connectivity in brain areas that are involved in numerous functions, including pain processing, sensation, and movement. It is possible that the alterations in these networks may contribute to other common chronic pain comorbidities, such as disrupted cognitions or anxiety. Previous research shows that during experimentally-induced pain, these networks can return to initial levels of functioning, indicating that these functional alterations are likely not permanent.

Background and aims Systematic and regular pain assessment has been shown to improve pain management. Well-functioning pain assessments require using strategies informed by well-established theory. This study evaluates documented pain assessments reported in medical records and by patients, including reassessment using a Numeric Rating Scale (NRS) after patients receive rescue medication. Methods Documentation surveys (DS) and patient surveys (PS) were performed at baseline (BL), after six months, and after 12 months in 44 in-patient wards at the three hospitals in Östergötland County, Sweden. Nurses and nurse assistants received training on pain assessment and support. The Knowledge to Action Framework guided the implementation of new routines. Results According to DS pain assessment using NRS, pain assessment increased significantly: from 7% at baseline to 36% at 12 months ( p < 0.001). For PS, corresponding numbers were 33% and 50% ( p < 0.001). According to the PS, the proportion of patients who received rescue medication and who had been reassessed increased from 73% to 86% ( p = 0.003). The use of NRS to document pain assessment after patients received rescue medication increased significantly (4% vs. 17%; p < 0.001). Conclusions After implementing education and support strategies, systematic pain assessment increased, an encouraging finding considering the complex contexts of in-patient facilities. However, the achieved assessment levels and especially reassessments related to rescue medication were clinically unsatisfactory. Future studies should include nursing staff and physicians and increase interactivity such as providing online education support. A discrepancy between documented and reported reassessment in association with given rescue medication might indicate that nurses need better ways to provide pain relief. Implications The fairly low level of patient-reported pain via NRS and documented use of NRS before and 12 months after the educational programme stresses the need for education on pain management in nursing education. Implementations differing from traditional educational attempts such as interactive implementations might complement educational programmes given at the work place. Standardized routines for pain management that include the possibility for nurses to deliver pain medication within well-defined margins might improve pain management and increase the use of pain assessments. Further research is needed that examines the large discrepancy between patient-reported pain management and documentation in the medical recording system of transient pain.

Background and aims Pain is known to have a disruptive effect on cognitive performance, but prior studies have used highly constrained laboratory tasks that lack ecological validity. In everyday life people are required to complete more complex sets of tasks, prioritising task completion and recalling lists of tasks which need to be completed, and these tasks continue to be attempted during episodes or states of pain. The present study therefore examined the impact of thermal induced pain on a simulated errand task. Methods Fifty-five healthy adults (36 female) performed the Edinburgh Virtual Errands Task (EVET) either during a painful thermal sensation or with no concurrent pain. Participants also completed the Experience of Cognitive Intrusion of Pain (ECIP) questionnaire to measure their self-reported cognitive impact of pain in general life. Results Participants who completed the EVET task in pain and who self-reported high intrusion of pain made significantly more errors than those who reported lower intrusion on the ECIP. Conclusions Findings here support the growing literature that suggests that pain has a significant impact on cognitive performance. Furthermore, these findings support the developing literature suggesting that this relationship is complex when considering real world cognition, and that self-report on the ECIP relates well to performance on a task designed to reflect the complexities of everyday living. Implications If extrapolated to chronic pain populations, these data suggest that pain during complex multitasking performance may have a significant impact on the number of errors made. For people highly vulnerable to cognitive intrusion by pain, this may result in errors such as selecting the wrong location or item to perform tasks, or forgetting to perform these tasks at the correct time. If these findings are shown to extend to chronic pain populations then occupational support to manage complex task performance, using for example diaries/electronic reminders, may help to improve everyday abilities.

Background/aims This longitudinal study investigated the pattern of change in pain intensity, disability, and depression in 232 chronic pain patients who were followed up for 2 years since pain onset. Most studies that have investigated changes in these variables over time have used participants who had already been in pain for more than 3 months. Few studies have followed up individuals from the acute phase onward and such studies used traditional statistical methods that cannot identify transition points over time or measure inter-individual variability. Methods We followed up individuals with chronic pain from pain onset up to 18 months and we examined their pain intensity, disability and depression trajectories using a modelling approach that allows to account for between and within-individual variability. We compared three patterns of change based on theoretical criterions: a simple linear growth model; a spline model with a 3-month transition point; and a spline model with a 6-month transition point. Time with pain was selected as time metric to characterise the change in these variables in the transition from acute to chronic pain. Sex and age differences were also examined. Results The results showed that the pain intensity trajectory was best represented by the spline model with a 3-month transition point, whereas disability and depression were best explained by linear growth models. There were sex differences at intercept level in all the models. There were age differences at baseline for pain intensity. No sex or age differences were found for the slope. Conclusions Pain intensity decreased in the first 3 months but underwent no further change. Disability and depression slightly but constantly decreased over time. Although women and older individuals are more likely to report higher pain intensity or pain-related disability in the first three months with pain, no differences by sex or age appear to be associated with the changes in pain intensity, depression and disability through the process of chronification. Implications Our findings suggest that pain chronification could be considered a continuous process and contribute to the ongoing discussion on the utility of standard classifications of pain as acute or chronic from a clinical point of view. Clinical and intervention decisions based in these standard classifications should consider the differences in the trajectories of pain related variables over time. In addition, this article illustrates a statistical procedure that can be of utility to pain researchers.

Background and aim Diclofenac is widely prescribed for the treatment of pain. Several network meta-analyses (NMA), largely of published trials have evaluated the efficacy, tolerability, and safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The present NMA extends these analyses to unpublished older (legacy) diclofenac trials. Methods We identified randomised controlled trials (RCTs) of diclofenac with planned study duration of at least 4 weeks for the treatment of osteoarthritis (OA) from ‘legacy’ studies conducted by Novartis but not published in a peer reviewed journal or included in any previous pooled analyses. All studies reporting efficacy and/or safety of treatment with diclofenac or other active therapies or placebo were included. We used a Bayesian NMA model, and estimated relative treatment effects between pairwise treatments. Main outcomes included pain relief measured using visual analogue scale at 2, 4 and 12 weeks and patient global assessment (PGA) at 4 and 12 weeks for efficacy, all-cause withdrawals, and adverse events. Results A total of 19 RCTs (5030 patients) were included; 18 of which were double-blind and one singleblind. All studies were conducted before cyclooxygenase 2 inhibitors (COXIBs) became commercially available. Data permitted robust efficacy comparison between diclofenac and ibuprofen, but the amount of data for other comparators was limited. Diclofenac 150 mg/day was more efficacious than ibuprofen 1200 mg/day and had likely favourable outcomes for pain relief compared to ibuprofen 2400 mg/day. Diclofenac 100 mg/day had likely favourable outcomes compared to ibuprofen 1200 mg/day in alleviating pain. Based on PGA, diclofenac 150 mg/day was more efficacious and likely to be favourable than ibuprofen 1200 mg/day and 2400 mg/day, respectively. Risk of withdrawal due to all causes with diclofenac and ibuprofen were comparable. Diclofenac 150 mg/day was likely to have favourable efficacy and comparable tolerability with diclofenac 100 mg/day. Results comparing diclofenac and ibuprofen were similar to those from NMAs of published trials. Conclusions Results from these unpublished ‘legacy’ studies were similar to those from NMAs of published trials. The favourable efficacy results of diclofenac compared to ibuprofen expand the amount of available evidence comparing these two NSAIDs. The overall benefit-risk profile of diclofenac was comparable to that of ibuprofen in OA. Implications The present NMA results reassures that the older unpublished blinded trials have similar results compared to more recently published trials and also contributes to increase the transparency of clinical trials performed with diclofenac further back in the past.

Graphical Abstract Abstract Background and aims Anxiety and fear are increasingly seen as related, but distinct concepts, with anxiety describing a reaction to unclear or future threats, and fear to immediate threats. Anxiety and fear both play influential roles in pain. Yet, the two concepts have not been clearly distinguished in pain research. Their reported intensity differs between the sexes, and sex differences in the way pain anxiety and fear of (re)injury relate to pain intensity have been found separately in previous studies. However, they seem to be of a curious nature: In one study, pain anxiety was associated with elevated pain intensity in men, while in another, fear of (re)injury was associated with elevated pain intensity in women. This indicates a moderator effect of sex. The present study is the first to unite previous findings, and to show a more integrative picture, by examining and discussing this moderator effect of sex in a joint study of both pain-related anxiety and fear in both sexes. Methods In 133 patients (mean age 43.6 years, 62% female) with chronic low back pain (mean duration 7.7 years), sex differences were examined with correlations and a multiple linear regression analysis with interaction terms. Differences between subgroups of low and high anxiety/fear were explored via t -tests, following previous studies. Results Sex was supported as a moderator in the association of pain intensity with pain anxiety (PASS-20), and fear of (re)injury (TSK). Higher pain intensity was linked to higher pain anxiety only in men, and to higher fear of (re)injury only in women. A basic regression model with fear, anxiety, sex and disability as predictors ( R 2 = .14, F (4,123) = 3.24, p = .042) was significantly improved by the addition of the interaction terms Fear×Sex and Anxiety × Sex ( R 2 = .18, F (2,121) = 4.90, p = .001), which were both shown as significant predictors for pain intensity. Further t -tests revealed a significant difference in pain intensity between high and low anxiety in men ( t (47) = −2.34, p = .023, d = −.43), but not in women. Likewise, a significant difference in pain intensity between high and low fear showed in women ( t (80) = −2.28, p = .025, d = −.42), but not in men. Conclusions The results support a moderator effect of sex and suggest differential mechanisms between the sexes in pain anxiety and fear in development and maintenance of back pain. The current study is the first to report and analyse this moderator effect. As potential underlying mechanisms, evolution and socialization are discussed, which may elucidate why fear might be more relevant for pain in women, and anxiety more relevant for pain in men. Implications The results indicate the need for a more cautious conceptual separation of fear and anxiety in research. Future studies on fear and anxiety in pain should be aware of the distinction, in order to avoid reporting only half of the picture. The next step would be to solidify the results in different samples, and to examine whether a distinction between anxiety and fear in the sexes could have any benefit in pain treatment.

Background and purpose (aims) Measurement error of intraoral quantitative sensory testing (QST) has been assessed using traditional methods for reliability, such as intraclass correlation coefficients (ICCs). Most studies reporting QST reliability focused on assessingone source of measurement error at a time, e.g., inter- or intra-examiner (test–retest) reliabilities and employed two examiners to test inter-examiner reliability. The present study used a complex design with multiple examiners with the aim of assessing the reliability of intraoral QST taking account of multiple sources of error simultaneously. Methods Four examiners of varied experience assessed 12 healthy participants in two visits separated by 48 h. Seven QST procedures to determine sensory thresholds were used: cold detection (CDT), warmth detection (WDT), cold pain (CPT), heat pain (HPT), mechanical detection (MDT), mechanical pain (MPT) and pressure pain (PPT). Mixed linear models were used to estimate variance components for reliability assessment; dependability coefficients were used to simulate alternative test scenarios. Results Most intraoral QST variability arose from differences between participants (8.8–30.5%), differences between visits within participant (4.6–52.8%), and error (13.3–28.3%). For QST procedures other than CDT and MDT, increasing the number of visits with a single examiner performing the procedures would lead to improved dependability (dependability coefficient ranges: single visit, four examiners = 0.12–0.54; four visits, single examiner = 0.27–0.68). A wide range of reliabilities for QST procedures, as measured by ICCs, was noted for inter- (0.39–0.80) and intra-examiner (0.10–0.62) variation. Conclusion Reliability of sensory testing can be better assessed by measuring multiple sources of error simultaneously instead of focusing on one source at a time. In experimental settings, large numbers of participants are needed to obtain accurate estimates of treatment effects based on QST measurements. This is different from clinical use, where variation between persons (the person main effect) is not a concern because clinical measurements are done on a single person. Implications Future studies assessing sensorytestingreliabilityinboth clinicaland experimental settings would benefit from routinely measuring multiple sources of error. The methods and results of this study can be used by clinical researchers to improve assessment of measurement error related to intraoral sensorytesting. This should lead to improved resource allocation when designing studies that use intraoral quantitative sensory testing in clinical and experimental settings. © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Background Pain assessment by Numeric Rating Scale (NRS) is considered to be good clinical practice, but objective pain assessment is still a challenge. Near infrared spectroscopy (NIRS) measures cerebral tissue oxygen saturation (SctO 2 ) that increases with cortical-neuronal activity and may provide point-of-care bedside pain monitoring. Analogous to promising studies in newborns, we hypothesize that different levels of SctO 2 can probably quantify pain intensity. SctO 2 may increase following painful in contrast to non-painful or sham stimuli and may correlate with pain intensity as assessed by NRS in volunteers. Methods Twenty healthy male students (24.2±1.9 years), recruited via local advertising, were consecutively included in a sequence-randomized, sham-controlled, single-blinded study. SctO 2 was recorded continuously with two NIRS sensors on the forehead. After resting, four stimuli were applied in a random order on the right forearm (unexpected and expected electrical pain, expected non-painful and sham stimuli). Blinded subjects were asked to rate each stimulus on NRS. Statistics: RM-ANOVA; Wilcoxon or paired Student t-test; Spearman’s rank correlation; P < .05. Results Resting volunteers showed SctO 2 of 72.65%±3.39. SctO 2 significantly increased for about 60 to 70s until a maximum after unexpected painful (74.62%±3.9; P = .022) and sham stimuli (74.07%±3.23; P =.014). Expected painful ( P =.139) and non-painful stimuli ( P =.455) resulted in no changes in SctO 2 . NRS scores (median, IQR) were rated significantly higher after expected (5.25, 3.5 to 6.75) than after unexpected (4.5, 3 to 5; P = .008) pain. No strong correlation was found between NRS and SctO 2 . Conclusions and Implications Contrary to our expectations, measuring SctO 2 via a two-channel NIRS is not able to remediate the lack of objective bedside pain assessment under standardized experimental conditions in alert adults.

Graphical Abstract Abstract Background and purpose Over the last years, concern has been expressed about adolescents’ possible liberal attitude towards – and use of – non-prescription analgesics. A high consumption of analgesics is unfortunate as it may lead to various harmful effects and worsening of headache. In order to address this challenge, it is necessary to achieve a more extensive knowledge about adolescent consumption. The main aim of this study was to examine the association between adolescent and parental use of nonprescription analgesics, taking into account headache as well as other somatic pain. The effects of parental prescription analgesics use was a secondary aim. Methods The study is based on data from two cross-sectional health studies conducted in 2005 and 2012 in Norway, including 646 adolescents and an accompanying parent. By using sample weights, the final weighted sample used in the analysis was 1326. Data was collected through postal questionnaires to parents and adolescents as well as parental telephone interviews. Questionnaires included questions on different pain locations and the pain for each location was graded according to how troubling the pain was. Medication data on prescription and non-prescription analgesics was from telephone interviews and was quantified based on the pattern over the past 4 weeks. Multivariate logistic regression models and complex samples analyses were used. Results 20% of adolescents were reported as using non-prescription analgesics during the previous 4 weeks. Girls were more often reported to use non-prescription analgesics than boys. Headache and all other somatic pain locations except back pain were reported more frequently among girls while boys more frequently reported back pain. There was a clear association between the use of non-prescription analgesics and headache with 34% of adolescents with headache using non-prescription analgesics versus 19% of adolescents with other somatic pain and 14% of adolescents not reporting pain. Among adolescents reporting headache, 9% were reported to use non-prescription analgesics daily or almost daily versus 3% and 2% among those reporting other somatic pain and reporting no pain respectively. In addition, parental use of non-prescription analgesics was a strong independent predictor of adolescent use (adjusted OR 1.69 for boys, 1.54 for girls). This relationship increased when the adolescents were less bothered by headache themselves. Conclusion Headache is the dominant medication-driving pain for non-prescription analgesics among adolescents but parental medication use of non-prescription analgesics also strongly influences adolescent use. Implications There is a need for health services to improve information to parents and adolescents about risks associated with use of analgesics and also to work on prophylactic strategies focusing on adolescents. Parents should be made aware that their medicine use strongly influences that of their children.

Background and aims Pain is highly prevalent in advanced cancer, and in some patients refractory to conventional opioid treatment. For these patients, invasive methods of pain relief should be considered. Spinal administration of opioids has been shown to be an effective alternative in refractory cancer pain. The aim of this retrospective study was to collect information on the use of spinal analgesia for cancer pain in Helsinki University Hospital. Methods A retrospective patient chart study of all cancer patients with spinal analgesia, either intrathecal or epidural, in a single academic center during a five year period ( n = 60). Results Forty-four patients were treated with intrathecal (IT) and sixteen with epidural (EP) technique. The most common indication for spinal analgesia was pain refractory to systemic analgesics. Good analgesia was achieved in 50% and 70% of the patients in the EP and IT groups, respectively. The median daily systemic opioid doses prior to spinal analgesia were 874.5 mg and 730.5 mg as oral morphine equivalents in the IT and EP groups, respectively. The systemic opioid could be discontinued or significantly reduced in 83% of the patients. Morphine was used in all IT infusions and most EP infusions, mostly combined with bupivacaine 10mg (IT) or 66mg (EP). The median starting doses of morphine were 3 mg/day (IT) and 19 mg/day (EP) and were increased during titration 27% to 3.8 mg/day (IT) and 91% to 36.2 mg/day (EP). Clonidine (median 0.015 mg/day IT and 0.15 mg/day EP) and/or ketamine were used as adjuvants. The average titration time to stable analgesia was 7–9 days. Numbness in lower limbs was reported by 24% of the IT group. On average, catheters were placed 98 and 61 days before death in IT and EP groups, respectively. No serious complications occurred. Catheter dislocation occurred in 27% of all sixty patients during follow-up. Treatment was discontinued in 10 patients because of catheter dislocation ( n =7) or local infection ( n = 3). Conclusions and implications Spinal administration of opioids is a safe and effective method of pain management in patients with severe cancer pain and can greatly reduce the need of systemic opioids. We are implementing closer collaboration with oncologists to provide spinal analgesia to more patients and earlier to reduce suffering. Catheter dislocation led to discontinuation of spinal analgesia in 17% of the patients and we are evaluating new ways to prevent catheter dislocation. The initial median spinal opioid dose was too low in both groups, and we are now using higher initial doses. A common adverse effect was numbness of the lower limbs, regardless of the relatively low doses of spinal bupivacaine. We now use lower doses and introduce the intrathecal catheter higher at L1–2 to reduce motor blockade at the level of conus. As an initial intrathecal infusions we suggest: morphine dose calculated using an oral to intrathecal ratio of 1:100 (unless the patient is elderly or already drowsy), clonidine dose 30μg/day and bupivacaine dose 7.5 mg/day.

Graphical Abstract Abstract Background Only two out of the five existing randomized studies have reported better results from fusion surgery for chronic low back pain (CLBP) compared to conservative treatment. In these studies the back symptoms of the patients were described simply as “chronic low back pain”. One possible reason for the modest results of surgery is the lack of a description of specified symptoms that might be related to a painful segment/disc, and patient selection may therefore be more or less a matter of chance. Previous prospective studies including facet joint injections and discography and eventually MRI have failed to identify patients with a painful segment/disc that will benefit from fusion surgery. Purpose Our purpose was to analyse in detail the pre-operative symptoms and signs presented by patients who showed substantial relief from their back pain following spinal fusion surgery with the aim of possibly finding a pain pattern indicating segmental, discogenic pain. Methods We analysed 40 consecutive patients, mean age 41 years, with a history of disabling low back pain for a mean of 7.7 years. Before surgery the patients completed a detailed questionnaire concerning various aspects of their back pain, and findings at clinical examination were thoroughly noted. Monosegmental posterior lumbar interbody fusion without internal fixation was performed using microsurgical technique. Outcome was assessed at 1, 2 and 4 years after surgery and finally at 18 years, using selfreporting measures and assessment by an independent examiner. Assessment at 18 years applied the Balanced Inventory for Spinal Disorders Questionnaire and the Roland-Morris Disability Questionnaire. Results According to the independent observer’s assessment at two years 27 of the 40 patients were much improved. Analysis of the pre-operative depiction of the back symptoms of this group revealed a rather uniform pattern, the most important being: dominating back pain originating in the midline of the spine, with a dull, aching character and stabbing pain in the same area provoked by sudden movements. Most patients in this group also had diffuse pain radiation of various extension down one or both legs and often bladder dysfunction with frequency. At clinical examination, localized interspinal tenderness was observed within the spinal area in question and the patient’s back pain was provoked by pressure in that area and by tapping a neighbouring spinous process. At 18 years after surgery 19 patients assessed themselves as much improved. At that time 5 of them had pension due to age, 7 early pension, one worked full time and six patients part time. Eleven patients were re-operated due to defect bony healing. Conclusions The results may suggest that the use of a detailed symptom analysis and clinical examination may make it possible to select a subgroup of patients within the CLBP group likely to have better outcome following fusion surgery. Implications The next step would be to execute prospective studies and if our findings concerning back pain details and signs among CLPB patients can be confirmed this can provide for more accurate selection of patients suitable for fusion surgery.

Background and aims Several methods for pain management following total hip arthroplasty (THA) have been described but the best postoperative pain management technique remains uncertain. We compared surgeon applied local infiltration analgesia (LIA) with anaesthesiologist performed femoral nerve block (FNB) using ultrasound. The primary aim was to assess pain intensity 24 h after THA. Methods In this randomized, double-blind study, 56 patients (ASA I-III) undergoing THA consented to participate. In Group FNB, patients received an ultrasound-guided femoral nerve block using 30 ml of ropivacaine 7.5 mg/ml (225 mg) while Group LIA received a similar volume of saline. Spinal anaesthesia was then performed and bupivacaine heavy, 3–3.5 ml injected depending on patient characteristics. During surgery, patients in Group LIA received a mixture of 300 mg (150 ml) ropivacaine, ketorolac 30 mg (1 ml) and adrenaline 0.5 mg (0.5 ml) (total volume 151.5 ml) peri-articularly and subcutaneously while Group FNB received 151.5 ml of saline peri-articularly in a systematic way by the surgeon. A multi-hole catheter was placed with the tip placed intra-articularly at the end of surgery in both groups. After 23 h, the LIA mixture consisting of 20 ml ropivacaine (7.5 mg/ml), ketorolac 30 mg (1 ml), adrenaline 0.1 mg (1 ml) (total volume 22 ml) was injected in Group LIA and the same volume of saline in Group FNB. Postoperative pain, analgesic consumption (postoperative and post-discharge), side effects, home discharge, quality of life and hip function were recorded, the latter up to 6 months after surgery. Results Postoperative pain intensity was significantly lower in Group LIA compared to Group FNB during mobilization at 24 h (primary endpoint), mean difference 1.8 NRS units (95% CI 0.7–2.9) ( P = 0.006), at rest after 4 h ( P = 0.029) and on standing after 24 ( P = 0.0003) and 48 h ( P = 0.043). Rescue morphine consumption was also significantly lower in Group LIA during 0–24, mean difference 13.5 mg (95% CI, 6.1–20.9) ( P = 0.002) postoperatively. Motor block was greater at 6 h ( P = 0.029) postoperatively in Group FNB. Two patients (one in each group) had persistent post-surgical pain (NRS > 3) at 3 months (3.6%) but none at 6 month. No other differences were found between the groups. Conclusion Local infiltration analgesia significantly reduces pain intensity on standing and mobilization, and rescue analgesic consumption compared to femoral nerve block without causing significant side effects. The superior analgesia in the LIA group may result from the secondary injection at 23 h postoperatively and needs to be furtherevaluated in future studies. No differences were found in home discharge, quality of life and hip dysfunction between the groups. Implication Local infiltration analgesia is the preferred method for postoperative pain management following THA compared to single-shot femoral nerve block. © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Background and aims Post-operative pain after caesarean operation remains one of the major complains after delivery. With the rising rate of caesarean deliveries, the assessment and management of acute pain has become a major concern for medical professionals in Ghana. The aim was to determine the association between the neuroplasticity of pain and depression using a postoperative pain assessment among women after caesarean section in Ghana. Methods A descriptive pilot studies consisting of 54 women who have undergone caesarean operations and reported of acute pain after three months were conducted in King David Hospital and Neptune Medical centre. A purposeful sampling was used to complete the Numeric Pain Scale (NPS) and the Wong-Baker FACES Pain Rating Scale to justify the inclusion criteria. While the Pain Quality Assessment Scale (PQAS) and the Beck Depression Inventory (BDI) were completed by participant. Results On the characteristics of their pain respondents scored above 7, on average, for hot pains (7.04 ±2.028, minimum of 5 and maximum of 10), unpleasant pains (7.33±1.907, minimum of 5 and maximum of 10), intense and deep pain (7.35 ±1.825, minimum of 5 and maximum of 10) and intense but surface (7.38 ±1.784, minimum of 5 and maximum of 10), each with a minimum of 5 and a maximum of 10. This implies that for each of those types of pain, respondents scored very high levels of intensity. Similarly, on intensity of pain sensation (6.43 ±1.814, minimum of 5 and maximum of 10), sharpness of pain (6.53±1.772, minimum of 5 and maximum of 10), how dull their pains felt (6.38 ±2.603, minimum of 0 and maximum of 10) sensitiveness of their skins (6.75 ±1.9, minimum of 4 and maximum of 10) and how itchy (6.98±2.137, minimum of 4 and maximum of 10) their skins felt with their respective standard deviations. On the depression scale, more than half of the respondents (51.9%) captured in this study had moderate depression. Conclusions We ultimately sought to conduct a test of association between ten indicators of quality of pain and depression. There turned out to be significant association between intensity of pain and depression (χ 2 = 21.507; p < 0.001) simply implying that where there is a rise in intensity of pain, there is likely going to be depression. There was also a significant association between sharp sensation and depression (χ 2 =31.256).

Aims To explore the association between static (hyperalgesia) and dynamic (allodynia) pressure algometry for assessing muscle pain hypersensitivity in women with migraine. Methods One hundred and twenty women with migraine (42% chronic, 58% episodic) participated. Dynamic muscle allodynia was assessed with a dynamic pressure algometry set (Aalborg University, Denmark © ) consisting of 11 rollers with fixed pressure levels from 500 g to 5300 g. Each roller was moved at a speed of 0.5 cm/s over a 60 mm horizontal line covering the temporalis muscle. Dynamic pain threshold (DPT-pressure level of the first painful roller) was calculated on each side of the head. Migraine pain features were collected on a headache-diary. As golden standard, static pressure pain thresholds (PPTs) were assessed over the temporalis muscle, C5/C6 joint, second metacarpal and tibialis anterior to assess widespread pressure hyperalgesia. Results Side-to-side consistency between DPT ( r = 0.769, P < 0.001) was found. DPT was moderately associated with widespread PPTs (0.364 > r > 0.769, all P < 0.001). No significant association with migraine pain features (frequency, intensity or duration of migraine attack) were observed (all, P > 0.129). Associations were similar in women with episodic or chronic migraine. Conclusions Dynamic pressure algometry was valid for assessing dynamic mechanical muscle allodynia in migraine. DPT was associated with widespread static muscle hyperalgesia independently of migraine frequency supporting that dynamic muscle allodynia in the trigeminal area is consistent with generalized pressure pain hyperalgesia. Assessing dynamic deep somatic tissue sensitivity may provide a new tool for assessing treatment effects.

Aims Some evidence supports that referred pain elicited by active trigger points (TrPs) reproduces some features of tension type headache (TTH). Our aim was to investigate the association between the number of active TrPs and health-related quality of life TTH. Methods Patients with TTH diagnosed by experienced neurologists according to the last International Headache Classification (ICHD-III) were included. Exclusion criteria included other primary headaches, medication overuse headache, whiplash injury or fibromyalgia. TrPs were bilaterally explored within the masseter, temporalis, trapezius, sternocleidomastoid, splenius capitis, and suboccipital. Health-related quality of life was assessed with the SF-36 questionnaire including 8 domains: physical functioning, physical role, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Higher scores represent better quality of life. Spearman correlation coefficients were used to determine correlations between the active TrPs and SF-36. Results Two hundred and two patients (mean age: 45±12 years) with a headache frequency of 17±7 days/month participated. Each patient with TTH exhibited 4.7±2.9 active TrPs. The number of active TrPs showed moderate weak negative associations with bodily pain ( r s : −0.216; P =0.002), emotional role ( r s : -0.185; P = 0.008) and vitality ( r s : –0.161; P = 0.02), but not with the remaining domains: the higher the number of active TrPs, the worse the emotional role and vitality and the higher the pain interference with daily life. These results were similar in both frequent episodic and chronic TTH. Conclusions The number of active TrPs was associated with sensory and emotional aspects of quality of life in a cohort of subjects with TTH.

Background Adjuvant chemotherapy with docetaxel and oxaliplatin increases survival in patients with high-risk breast and colorectal cancer, respectively, but may induce acute and chronic neurotoxicity. This study is a 5-year follow-up of chronic chemotherapy-induced peripheral neuropathy (CIPN). Methods In 2011–2012, 74 patients with high-risk colorectal cancer and 100 patients with high-risk breast cancer answered a questionnaire before, during and one year after receiving adjuvant chemotherapy with oxaliplatin and docetaxel, respectively. In 2016, a 5-year follow-up with the same questionnaire was performed in survivors. Results Fifty-two (36.5% women) of 74 patients (91%) treated with oxaliplatin and 80 (100% women) of 100 patients (85%) treated with docetaxel answered the questionnaire. The most common symptoms of CIPN were tingling in the hands (44.2% in the oxaliplatin (CI 95% 30.5; 58.7) and 36.3% in the docetaxel group (CI 95% 25.8; 47.8)) and feet (52.0% in the oxaliplatin (CI 95% 37.6; 66.0) and 37.5% (CI 95% 29.9; 49.0) in the docetaxel group) and numbness in the feet (34.6% in the oxaliplatin (CI 95% 22.0; 49.1) and 17.5% (CI 95% 9.9; 27.6) in the docetaxel group). Pain was present in the hands or feet in 28.9% of patients treated with oxaliplatin (CI 95% 17.12; 43.0) and 31.3% of patients treated with docetaxel (CI 95% 21.3; 42.6). Conclusions The results showed no major change in symptoms of neuropathy or pain from 1 to 5 years after chemotherapy. Symptoms of neuropathy were more common in patients treated with oxaliplatin.

Aims In temporomandibular disorders sufferers, muscle pain is more severe in individuals who have undergone a traumatic stress. Why stress exacerbates masticatory muscle pain in these individuals is not known. One possibility is that under conditions of stress there is an interaction between the sympathetic and sensory nervous systems. This study investigated whether trigeminal ganglion neurons that innervate the masseter muscle express α 1 adrenergic receptor subtypes to identify whether a direct interaction between the sympathetic and sensory nervous systems is feasible. Methods Masseter muscle ganglion neurons were identified by injection of the fluorescent dye fast blue into the masseter muscle of 4 Sprague Dawley rats (2 male, 2 female). Trigeminal ganglion sections were stained for α 1a , α 1b or α 1d adrenergic receptors, as well as the transient receptor potential vanilloid 1 (TrpV1) receptor. Sections were examined with a Leica confocal microscope. The percent of masseter ganglion neurons expressing each receptor was calculated. Results Masseter muscle ganglion neurons expressed α 1a (29 ± 9%), α 1b (34 ± 4%) and α 1 d (19 ± 13%) adrenergic receptors. Expression of all three α 1 receptor subtypes was higher in female rats than in male rats. Expression of α 1b receptors was more commonly found on larger diameter masseter ganglion neurons. Overall 11±3% of masseter ganglion neurons expressed the TrpV1 receptor, which suggests they served a nociceptive function. The TrpV1 receptor was co-expressed by about ~10% of α 1a and α 1b receptor positive masseter ganglion neurons. Conclusions Afferent fibers that innervate the masseter muscle express all three α 1 adrenergic receptor subtypes. Agonists at the α 1 receptor have been previously shown to depolarize trigeminal ganglion neurons, which suggests that activation of these receptors on masseter muscle afferents would be excitatory. The expression of α 1 receptors by putative nociceptors that innervate the masseter may permit a direct interaction between the sensory and sympathetic system that contributes to pain in this muscle.

Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

Aims Mechanical neck pain (MNP) and whiplash-associated disorders (WAD) represents two groups of subjects with a different pathogenesis, since current evidence supports that WAD subjects presents greater sensitization than MNP. Nevertheless, it is still unclear the relationship between neck pain, neck disability, widespread pressure pain hypersensitivity (sign of sensitization) and trigger points (TrPs) in these two groups of neck pain subjects. The aim of the current study was to investigate these associations in MNP and WAD subjects. Methods Forty-six MNP and fifty-one WAD subjects underwent the following examination: pressure pain thresholds (PPTs) in the upper trapezius and tibialis anterior muscles, TrP examination in the upper trapezius, and collection of neck disability and neck pain intensity. The examination was performed by an assessor blinded to subjects’ condition. Results A significant positive association between pain and disability ( P < 0.003), pain and PPT in the upper trapezius ( P < 0.041), pain and PPT in tibialis anterior ( P < 0.038), disability and PPT in upper trapezius ( P = 0.006) was found in both groups. Subjects with MNP showed significantly negative association between disability and PPT in the tibialis anterior ( P = 0.003). Subjects with active TrPs in the upper trapezius exhibited significantly higher neck pain intensity and neck disability and lower PPTs (all, P < 0.015), than those with latent TrPs in both groups. Conclusions Our results suggest that the association between pain, disability, and PPTs is similar in subjects with neck pain and not influenced by the origin of neck pain. The presence of active TrPs in upper trapezius in neck pain patients was related to higher pain intensity, related-disability and lower PPTs, compared to neck pain patients with latent TrPs in upper trapezius. Future studies are needed to determine the clinical role of these associations.

Aims Health history (medical conditions, comorbid musculoskeletal pain, surgical operation, long term intake of medications) may contribute to central sensitization. The duration and the number of the peripheral nociceptive input seem to play a crucial role in the development and maintenance of sensitization. No study has previously investigated these relationships. Our aim was to investigate the association between pressure pain thresholds (PPTs) and health history in patients with neck pain, and the role of active trigger points (TrPs) on PPTs. Methods Thirty-four subjects with mechanical neck pain and 34 with whiplash-associated neck pain participated. They underwent an assessment of PPTs over upper trapezius, extensor carpi radialis longus, and tibialis anterior muscles, and were screened for the presence of active TrPs in upper trapezius muscle. Further, patients fulfilled a questionnaire investigating health history outcomes number and duration. Results Significant negative correlations between all PPTs and the duration of health history outcomes were found in both groups (all, P < 0.02), with no correlations between PPTs and the number of health history outcomes (all, P > 0.15). Significant lower PPTs over upper trapezius, extensor carpi radialis longus, and tibialis anterior (all, P < 0.01) muscles were found in subjects with active TrPs as compared to those with latent TrPs. Conclusions Widespread pressure pain hypersensitivity was associated with the duration, but not the number, of health history outcomes suggesting that long-lasting health complains may act as triggering factor driving sensitization in individuals with neck pain regardless the origin of neck pain. Patients with active TrPs in the upper trapezius muscle showed higher widespread pressure sensitivity than those with latent TrPs. These data should be included in the assessment of neck pain subjects, as they may be useful for planning the management of their symptoms.

Background and aims Injury to peripheral nerves associated with trauma, amputation, or surgery may lead to the formation of neuromas that can cause severe pain. Unfortunately, neuromas are frequently refractory to medical and surgical treatment. This ongoing study examines whether neuromas are more frequent in patients experiencing pain after peripheral nerve injury or amputation than in patients without pain. Methods In this observational cohort study, 80 patients with peripheral nerve injury or amputation will be recruited. Patients will answer pain questionnaires and undergo a clinical examination with quantitative sensory testing performed within the area of spontaneous pain, including areas of brush-evoked allodynia and pinprick hyperalgesia. Neuromas are identified using ultrasound. Results Patient inclusion is ongoing. At present, fourteen amputees have participated in the study: nine males and four females, aged 38–77 years. Six patients had no neuromas. Stump pain in this group ranged from 0 to 8 and phantom pain from 0 to 10 on a numerical rating scale, 0–10. Eight patients had neuromas. Stump pain in this group ranged from 0 to 7 and phantom pain from 0 to 8. Further results will be presented at the congress. Conclusions Because of a limited number of patients included, it is not yet possible to conclude if neuromas are more frequent in patients with pain. Hopefully, this study will increase our understanding of the role of neuromas in patients with pain after peripheral nerve injury and amputation.

Aims The association between low fertility potential and an overweight is well recognized. In addition, a link between pain and overweight condition has been identified. However, it is not known whether overweight pain patients present any alterations in fertility potentials. Hence, the current study provided a profounder vision into the possible relation between an overweight condition, chronic musculoskeletal pain, and fertility potential in overweight male patients. Methods This “observational study” was based on 10 overweight chronic pain patients (OP and 10 healthy matched controls (OC) from the referrals to the orthopedic department at Aalborg University Hospital, Aalborg, Denmark. The study was approved by the regional Ethics Committee of the Northern Jutland, Denmark and conducted from June 2014 to December 2015. Semen samples were obtained from all participants and assessed for sperm concentration, motility, and kinematic parameters with the Sperm Class Analyzer (SCA®, Spain). Pressure pain thresholds (PPT) were also measured by a handheld pressure algometer in 16 pre-defined points of the subjects in both groups. Results The OP group demonstrated a decline in PPT values compared to the (OC); however, difference between the two was insignificant. But, the OP group showed a lower percentage of static and non-progressive motile sperm ( P < 0.05). The sperm kinematic parameters (progressive motility, VCL, VSL, VAP and BCF) also demonstrated a lower trend in OP group in comparison with the controls. Conclusions This study presented that sperm quality declines in overweight chronic pain patients. Since the control group consisted of pain free overweight individuals, we propose that chronic musculoskeletal pain could potentially affect sperm quality, distinct from what an overweight alone does to the male fertility potential. However, further investigation in overweight chronic pain patients of different types is required before a general conclusion can be made. In addition, mechanisms underlying such effects need further clarification.

Background and aims Maladaptive plasticity in neural circuits has been proposed in chronic musculoskeletal pain and has been discussed as a key component of the transition from acute to chronic pain. The induction of delayed onset muscle soreness (DOMS) in healthy individuals is one method that can be used to investigate the adaptations of neural circuits in response to several days of muscle hyperalgesia. The aim of this study was to determine the adaptations of the sensory cortex in response to muscle hyperalgesia induced by eccentric exercise of the wrist extensor muscles. It was hypothesized that muscle hyperalgesia would result in a facilitation of cortical somatosensory excitability, based on sensory evoked potentials evoked by electrical stimulation of the radial nerve. Methods Twelve healthy subjects performed eccentric exercise of the wrist extensors. Muscle soreness, pressure pain thresholds (PPTs) on the extensor carpi radialis (ECR) muscle, somatosensory evoked potentials (SEPs) based on 10 channel EEG recorded during electrical stimulation of the radial nerve were recorded before (Day0Pre), 2h (Day0Post), 2 days (Day2), and 6 days (Day6) after exercise. Results Compared to Day0Pre: (i) Muscle soreness increased at Day0Post and increased further at Day2 (both P < 0.05). (ii) Pressure pain thresholds decreased at Day2 ( P < 0.05), (iii) the peak-to-peak N30-P45 and P45-N60 amplitude of the sensory evoked potential from the central-parietal recording sites were increased at Day2 (both P < 0.05); (iv) reduction in ECR PPTs was correlated with an increase of the post-central P45 wave. Conclusions These data demonstrate that hyperalgesia developing across several days is accompanied by an increase in sensory cortical excitability. In addition, sensory cortical adaptation followed a similar temporal profile to increased sensitivity to pressure (PPTs). This model may be relevant for further understanding neural adaptation in the transition from acute to chronic pain.

Aims Bullying is a prevalent issue in society, with adverse effects ranging from psychological symptoms to somatic ailments like chronic pain. The purpose of this study was to generate new knowledge about the underlying mechanisms behind this association. Using an animal model, we investigated the changes in microRNA expression in plasma, in the pituitary gland and the adrenal gland following social stress. Methods A resident-intruder paradigm where male Sprague Dawley rats (intruders) were exposed to male Long Evans rats (resident) 1 h daily for a week was used. Bodyweight was measured and blood samples were collected throughout the experiment. Changes in plasma microRNA expression was determined by qPCR. Results Rats exposed to social stress showed reduced weight gain compared to controls. Preliminary results suggested that social stress increased the plasma expression of miR-146a-5p, miR-30c- 5p and miR-223-3p. Conclusions The data showed that social stress gives reduced weight gain and increased expression of several circulating microRNAs. How this affects the development of persistent pain remains to be investigated.

Aims Satellite glial cells (SGCs) are non-neuronal cells that entirely surround neurons within sensory ganglia. This unique structure allows SGC-neuron interactions. Altered cross-talk following nerve injury or inflammation is thought to contribute to pathogenesis of chronic pain. Release of extracellular vesicles in form of exosomes has been found to play a key role in cell-cell communication. However, release of exosomes from SGCs and their potential role in modulating pain remain unknown. Hence, this study aimed at identifying and characterizing shed exosomes from SGCs under normal and inflammatory conditions. Methods Fresh primary cultures of rat trigeminal ganglia (TG) were prepared from adult male Sprague–Dawley rats. Danish Animal Inspectorate approved the study protocol. Primary SGCs were kept in culture up to 21 days and were characterized by morphology and immunohistochemistry. Cultured SGCs were monitored under normal and LPS (50 ng/mL) treatment. Collection of conditioned media was performed over time and exosomes were isolated. Particle size distribution and total protein were determined by NTA and LC–MS/MS, respectively. Results SGCs formed small clusters, spread outwards to areas devoid of cells but remained spindle-like in appearance with larger cell bodies. The primary cultures of SGCs were clearly GS positive with a low expression of GFAP. LPS treatment led to higher GFAP expression. Particle size distribution showed that two third of the particles were in the exosomal size range. Upon LPS-stimulation, four proteins (histone H2B, ubiquitin-60S ribosomal, myosin-9, elongation factor 1-alpha) were found exclusively expressed compared to normal treated SGCs. Conclusions For the first time it was demonstrated that SGCs shed extracellular vesicles in exosomal size range. Mysoin-9 was identified as a possible novel marker of SGCs activation under inflammatory conditions. This protein plays a role in cell-cell adhesion and possibly contributes to SGC-SGC cross-talk upon inflammation which may consequently influence the excitability of nearby neurons.

Aims Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of chronic pain. In vitro, providing enough fresh primary SGCs poses some practical limitations; hence, frozen stocks of primary cells for culture could be an attractive alternative for cell-based studies or drug screening. This study was designed to investigate the morphology and marker expression of frozen and freshly isolated trigeminal SGCs under normal and inflammatory conditions. Methods SGCs from trigeminal ganglia of three male Sprague–Dawley rats and three frozen (sub cultured and passaged) batches of stored primary SGCs were cultured. Their morphology was observed by phase microscopy and the phenotype was characterized by immunocytochemistry of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). Lipopolysaccharide (LPS) was used to simulate a state of neurogenic inflammation in vivo . A pilot test was performed to determine the optimal concentration of LPS to activate SGCs based on GFAP expression. A long-term activation of the SGCs with 50 ng/mL LPS was chosen for further characterization. Results The fresh and frozen primary SGCs elicited similar phenotypes based on GS marker expression. However, frozen primary SGCs differed in terms of size and morphology. GFAP was constantly expressed in frozen primary SGCs regardless of LPS stimulation. Activation of primary fresh SGCs with LPS spread the GFAP expression from around the cell body throughout the longer processes and activation was only seen in the LPS treatment. Conclusions The phenotypic marker, GS was independent of culture conditions. There was no difference in upregulation of GFAP in thawed SGCs regardless of LPS stimulation. This indicates that freeze-thawing might activate SGCs and therefore frozen and passaged cells cannot be suitable for use in cell-based models for inflammation. Fresh primary cells are therefore optimal for studying SGCs under normal and inflammatory conditions.

Aims Does pre-emptive single dose intravenous tramadol produce a safe and effective postoperative analgesia? Methods Randomized, placebo controlled, single blinded clinical trial of pre-emptive intravenous tramadol 1 mg/kg in combination with IV midazolam in patients with dental fear. A “Pain diary” evaluates the efficacy. The safety is evaluated perioperative monitoring (SpO 2 and BP). Results Pain scored by VAS showed no differences between the groups. It took longer time to first rescue pill in tramadol vs. control group (157 vs. 110 min, p = 0.049). Desaturation (SpO 2 < 90%) was more commonly found in tramadol vs. placebo and control ( p < 0.01). Increasing systolic blood pressure in the control group. Diastolic blood pressure decrease in tramadol and placebo groups. In the tramadol group, we saw more frequently mild side effects. Conclusions Tramadol gave no reduction in postoperative pain but an increased frequency of desaturation and side effects. Other drugs or other doses ought to be tried for this kind of postoperative pain management.

Aims The exteroceptive sensory system is responsible for sensing external stimuli in relation to time and space. The aim of the study was to investigate the tempo-spatial properties of the exteroceptive system using laser heat and mechanical touch stimulation. Methods 13 healthy subjects were stimulated in the volar forearm. Each subject was stimulated using two paradigms, a continuous stimulation along a continuous line on the skin, and a simultaneous 2-point stimulation. The line stimulations were delivered in both a distal and proximal direction with lengths of 25, 50, 75, and 100 mm. The 2-point stimulations were delivered with a point-to-point distance ranging from 10 to 100 mm, in steps of 10 mm. Both paradigms were delivered using painful heat (laser) stimulation and mechanical (touch) stimulation. Following each stimulation, subjects had to report the intensity (0–10 NRS, 3 being pain threshold) and either direction (line stimuli) or number of perceived points (2-point stimuli). Results All four line lengths and both directions were reported correctly for all mechanical line stimulation (an accuracy of 100%). For laser line stimulation the directional discrimination threshold was 68.5 mm and 70.2 mm for distal and proximal directed stimuli, respectively. The 2-point discrimination threshold for heat stimulation (67.9 mm) was higher than for the mechanical stimulation (34.5 mm). NRS was significant higher for laser stimulations than for the mechanical stimulation for both line and 2-point stimulations. NRS increased both with line length and distance between the two points (ANOVA, p < 0.001). The average NRS was 3.15 and 0.91 for laser line and mechanical line stimulations, respectively. For 2-point stimulation the average NRS was 3.72 and 1.06 for laser and mechanical stimulations, respectively. Conclusions The findings indicate that the tempo-spatial acuity of the exteroceptive system is lower for noxious stimuli than for innoxious stimuli. This is possible due to the larger receptive fields of nociceptive neurons and/or less lateral inhibition.

Aims The spatial alternation of innocuous cold and warm stimuli on the skin can paradoxically provoke a hot, burning sensation, known as the thermal-grill illusion (TGI). Whether the TGI depends on spinal or supraspinal integration mechanisms is still debated. To assess whether the TGI can be accounted by integration of cold and warm afferent signals in the spinal cord, we leveraged anatomical knowledge on the spatial arrangement of dermatomes and spinal segmental projections. Methods We stimulated a series of skin locations on the right arm using one cold (∼20 °C) and one warm thermode (∼40°C). The two stimulus locations had identical physical distance on the skin. However, the distance between the cold and heat projection signals in the spinal cord varied across three conditions. Cold and warm inputs were delivered (1) within the same dermatome (e.g., C5–C5); (2) across the dermatome boundary of two adjacent spinal segments (e.g., C5–C6); (3) across the dermatome boundary of two non-adjacent spinal segments (e.g., C5–T1). In two experiments, we obtained an estimate of the strength of the TGI by asking 32 healthy participants to complete a temperature matching task. Results Participants overestimated the actual average temperature of the two thermodes (Exp. 1) and the cold temperature of one of the two thermodes (Exp. 2). However, this effect was significantly larger when cold and heat stimuli were delivered within the same dermatome (+6.57 ± 3.99°C and +9.88 ± 5.60 °C) or between dermatomes projecting to adjacent spinal segments (+6.26 ±4.44°C and +9.48 ± 5.83 °C), compared to when cold and heat stimuli projected to non-adjacent spinal segments (+3.46 ± 4.46 °C and +4.80 ± 3.21 °C). Conclusions These results demonstrate that the strength of the illusion is modulated by the segmental distance between cold and heat spinal signals, and show that the perceived quality and intensity of thermal stimuli depends upon low-level spatial summation mechanisms in the spinal cord.

Aims Migraine headache is a recurrent incapacitating neurovascular disorder. A combination of events occurring within the trigeminovascular system has been suggested to underlie migraine pathogenesis, including release of inflammatory neuropeptides with subsequent effects on meningeal vessels and sensory transmission. Increased craniofacial muscle tenderness is also present in patients with migraine and a lower β-endorphin concentration has been observed in these patients. Several external factors have been identified, which can modulate migraine. One such factor is cocoa, though controversies still exist whether this substance exerts pro-algesic or analgesic effects. The present study evaluated effects of pure cocoa on a mechanically-induced headache model in healthy individuals. Serum β-endorphin concentrations were also measured to identify if any changes occurred in response to cocoa consumption. Methods Healthy volunteers (8 men and 7 women, average age: 22±1.8 years) participated in a crossover study (approval number: N-20160015) consisting of two sessions with consumption of water or cocoa. A mechanical headband (custom-made, Aalborg University) was utilized to induce a moderate headache with pain rated as 4 on a Visual Analogue Scale (VAS 0–10 ). In each session Pressure Pain Threshold (PPT) was measured by a hand held algometer at temporalis muscles and blood samples were collected to assess β-endorphin levels by ELISA. ANOVA analysis and independent two-sample t-tests were performed for comparisons. P < 0.05 was considered as significant. Results Consumption of cocoa compared to water did not change the pressure sensitivity in the craniofacial region without mechanical headband. No changes occurred in PPT with the mechanical headband either.Regardless of substance consumption (water/cocoa), endorphin levels remained unchanged. Conclusions Findings demonstrated that pure cocoa in the applied concentration and within the timeline of this study did not seem to exert any analgesic or pro-algesic effect on the mechanical sensitivity of craniofacial muscles or β-endorphin levels.

Aims Opioid treatment is associated with gastrointestinal (GI) side effects, known as opioid-induced bowel dysfunction (OIBD). Symptoms of OIBD are caused by opioid receptor activation in the enteric nervous system, which results in increased GI transit time and increased faecal volume in the colon. OIBD can be experimentally induced in healthy participants through oral oxycodone treatment. The aim of this study was to investigate whether administration of naloxegol, a peripherally restricted opioid antagonist, could reduce GI symptoms, GI transit time, and colorectal volume, using an experimental model of OIBD. Methods In a double blind crossover trial, twenty-five healthy males were randomly assigned to a six day treatment of oral oxycodone in combination with either oral naloxegol or placebo. At baseline and at day six, participants filled in the Patient Assessment of Constipation Symptom questionnaire, and colorectal volume was quantified with a magnetic resonance imaging method. Participants swallowed a small electromagnetic capsule, which allowed determination of total and segmental GI transit times, using the 3D-Transit system. Results In the established model of oxycodone induced OIBD, fewer GI symptoms were observed during naloxegol treatment, compared to placebo ( P <0.01). Naloxegol decreased median total transit time by 27% (56 vs 71 h, P < 0.05) and decreased colorectal transit time by 33% (45 vs 59 h, P < 0.01), compared to placebo. No difference in colorectal volume was found between the two treatments. Conclusions In an experimental model of OIBD, GI symptoms and GI transit time were reduced during treatment with naloxegol, compared to placebo. However, naloxegol treatment did not reduce colorectal volume. These findings add information on the potential of naloxegol to be used in prevention and treatment of OIBD.

Aims The incidence of chronic pain after total knee replacement (TKR) is approx. 20%, why preoperative risk factors for the development of chronic postoperative pain are highly warranted. Studies have indicated that preoperative inflammatory markers hold prognostic information for the development of chronic postoperative pain. Long-non-coding-RNA (lncRNA) regulates the expression of genes related with e.g. inflammation. The current study aimed to investigate the preoperative influence of lncRNA on the development of chronic postoperative pain following TKR. Methods 24 patients, who developed chronic postoperative pain and 12 patients with painfree recovery, were sampled from a larger clinical study. Preoperative serum samples were obtained from all patients and analyzed for potential lncRNA candidates. Briefly, total RNA was extracted from serum using miRNeasy Mini kit.cDNA samples were pre-amplified with RT2lncRNAPreAMP Primer Mix that contained specific set of primers to target genes of Human RT2lncRNA Inflammatory Response & Autoimmunity PCR Array. Further, the reaction (25μl) will be aliquoted into the wells of RT2lncRNA PCR Array Human Inflammatory Response & Autoimmunity. LncRNA-expressions were compared between the two groups using student’s t-test. Results 19 patients were excluded due to the “cut-off” of the statistical analysis’s software that not included the samples because of genomic contamination, retro transcription and amplification’s low efficiency. A total of 13 patients were included (7 with pain, 6 without pain). The preliminary analysis found that the MEG3-lncRNA (implicated in tumor vascularization suppressing) were downregulated in patients who developed chronic postoperative pain compared to patients with a normal recovery (fold change: − 9.56, P < 0.05). Conclusions Preoperative MEG-3 is downregulated in patients in risk of developing chronic postoperative pain following TKR. Future research, in larger cohorts should further investigate the role of MEG3 and hence the improvement of the cartilage vascularization and other lncRNAs as predictive indicators for the development of chronic postoperative pain.

Background and aims Painful polyneuropathy (PPN) is a disabling complication of diabetes. This study aims to determine its prevalence and relationship with Quality of Life (QoL) in a nationwide prospective cohort of incident recently diagnosed Danish type 2 diabetic patients. Methods We sent a detailed questionnaire on neuropathy, pain and QoL to 6726 patients prospectively enrolled from general practitioners and hospital specialist outpatient clinics into the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Patients who reported pain in both feet and a score ≥3 on the Douleur Neuropathique (DN4) questionnaire were considered to have possible PPN. QoL and pain intensity were measured on a numeric rating scale (NRS, 0–10). The Michigan Neuropathy Screening Instrument (MNSI) was used to assess neuropathy. Results A total of 5371 (79.8%) returned a complete questionnaire. 848 (15.8%) recently diagnosed type 2 diabetic patients reported pain in both feet. Of the 619 patients with pain who completed the DN4 questionnaire, 404 (65.2%) had a DN4 score ≥ 3, corresponding to a prevalence in the total population of possible PPN of 10.3%. Mean pain intensity was 5.2 (SD 2.2) and 89% had a MNSI score ≥ 3. Patients with possible PPN had a substantially lower QoL score than those without PPN (median QoL score 6 versus 8 ( p < 0.001)), also when correcting for MNSI score. Conclusions Ten percent of newly diagnosed type 2 diabetic patients in Denmark had possible PPN. Patients with PPN had lower QoL than patients without PPN.

Aims Being a close relative of a chronic pain patient affects family life. No study has been carried out in Denmark to explore relatives’ life experiences and challenges while living with complexchronic pain patients. Hence, the aim of the study was to investigate the experiences of living with chronic pain patients from their spouses’ perspectives. In particular, this study focused on how spouses describe: (i) their everyday tasks and roles as a spouse; (ii) the types of changes and challenges that the pain condition brings into their partnership lives; (iii) a gender difference in these experiences; and (iv) the type of help they wish to receive from the healthcare system. Methods Two focus group interviews were conducted in Multidisciplinary Pain Center, Køge, including a total of 11 spouses (6 men). The spouses were contacted via their partners who were referred to public pain clinics. Focus group interview was chosen because is a suitable method for exploratory studies. The approach was phenomenological and transcriptions of interview records were used for analysis. Results Eight categories emerged from the data analysis: psychological burden, physical burden, the pain invisibility, roles, loss, worries concerning medicine, self-care, and needs concerning help and support. The differences between gender were vague. Spouses for whom the patient pain condition was a new situation (<1 year) appeared to worry more. Conclusions The study demonstrated that the spouses’ lives were dramatically affected. They had to support the family financially, do most of the household chores, be optimistic, a parent, and a pain care giver. The spouses experienced daily worries about several points including pain medicine by the patients. This study also highlighted an essential need for psychological support for coping with the changing life situation, the point that is currently neglected to a great extent.

Aims To evaluate the effect of widespread pain sensitization on postural stability during quiet standing tasks in patients with knee osteoarthritis. Methods Patients (56) stood quietly on a force platform for 1 min in 4 conditions (each repeated 3 times): (i) firm surface (FS) with open eyes (OE), (ii) FS with closed eyes (CE), (iii) soft foam surface (SS) with OE, and (iv) SS with CE. Postural stability was quantified by Center of Pressure (CoP) variables extracted from the force platform. Pressure pain thresholds (PPTs), were assessed bilaterally with a handheld pressure algometer (1 cm 2 probe) at: (i) four sites in the knee region (3 cm medial to the midpoint of the medial edge of the patella; 2 cm proximal to the superior edge of the patella; 3 cm lateral to the mid-point of the lateral edge of the patella; and centre of the patella), (ii) tibialis anterior muscle, and (iii) extensor carpi radialis longus muscle. The PPT values from tibialis anterior and extensor carpi radialis longus muscles were used to divide the patients in high and low sensitization groups (two-steps clustering). Results PPT values at bilateral knees sites were lower in the high sensitivity [median (range) of all sites: 423 (153, 1129) kPa] compared with low sensitivity group [822 (305, 2051) kPa] (P < 0.05). CoP range in the anterior–posterior direction was reduced in high sensitivity group (41±16 mm) compared with the low sensitivity group (51±16 mm) during the SS with CE (P < 0.05) condition. Conclusions The lower CoP Range suggests stiffer postural strategy in patients with higher widespread pain sensitivity compared with low sensitivity patients during sensory restrictions. The lack of mobility found in high sensitivity patients under such restrictions might be related to the impaired integration of sensory information due to the parallel processing of the nociceptive information.

Aims To assess the impact of dry needling on neural mechanosensitivity and grip strength in male subjects with a history of persistent pain in the neck/shoulder area. Methods Case series study. Eight male subjects (mean age 25±6.24 years) with a recurrent history of bilateral neck/shoulder pain for at least 6 months, and with symptoms provoked by neck/shoulder postures or movement were recruited from a University-based clinical research center. Measurements were taken at baseline, immediately after intervention, and fifteen days later, of the pressure pain threshold (PPT) over the median, ulnar, and radial nerves, and the tibialis anterior (TA) muscle. Secondary measures included free-pain grip strength with a hydraulic dynamometer. A therapist assessed the presence of latent (not spontaneously painful, but painful upon palpation) myofascial trigger points (MTrP) over the scalene, subclavius, pectoralis minor, infraspinatus and serratus posterior superior muscles, on the most painful side. Deep dry needling was then performed on the latent MtrP by quickly inserting and partially removing the needle from the MTrP until 2 local twitch responses were provoked. Results PPT over the nerve trunks significantly increased after intervention ( p < 0.05 for all locations). These changes remained constant in the second assessment, both in the treated ( p < 0.001 for median and ulnar nerves, and p = 0.004 for radial nerve), and the non-treated upper limb (median nerve p < 0.001, ulnar nerve p = 0.003, and radial nerve p = 0.006). No statistical significance was found for PPT over the TA muscle ( p > 0.05) or for grip strength ( p = 0.153 on the treated side, and p = 0.564 on the non-treated upper limb). Conclusions Dry needling on the cervicothoracic and shoulder areas may help to improve peripheral neural features over the brachial plexus nerve trunks in subjects with recurrent neck/shoulder pain. No effect was observed for grip strength.

Aims The incidence of persistent post-operative pain (PPP) is 30–85% in lower limb amputee (LLA) patients and identification of preoperative risk factors are warranted. Preoperative levels of anxiety, depression, pain catastrophizing, neuropathic pain and severe preoperative pain have previously been linked with PPP but such screening tools are not used in the clinical hospital setting. The aim of this study was to assess feasibility of using questionnaires for anxiety, depression, pain catastrophizing, neuropathic pain and preoperative pain levels in a clinical preoperative setting. Methods Patients scheduled for non-traumatic amputation of the lower leg or femur were recruited from three Danish hospitals. Exclusion criteria were surgery 4-weeks prior to LLA, same leg re-amputation, or inability to participate. Pre-operative values of anxiety, depression and catastrophizing were assessed using the Hospital Anxiety (A) and Depression(D) Scale (HADS) (cutoff: 8) and Pain Catastrophizing Scale (PCS) (cutoff =32). Neuropathic pain was assessed preoperatively using Pain-Detect-Questionnaire (PD-Q) (cutoff: 19). The maximum preoperative pain intensity was assessed using the Numeric Rating Scale (NRS; 0: no pain and 10: worst imaginable pain). Scores are presented as median values with interquartile range (Q1–Q3). Results Eight of 18 patients (5 females) completed this pilot study: median age 71 (range 56–83), 6 femur and two lower leg amputees. Nine of ten excluded patients were unable to complete the questionnaires and one patient was operated acutely. Median pre-operative HADS-D and -A scores were 7 (3–9, 50% ≥ cutoff) and 4 (1–8, 25% ≥ cutoff), pre-operative PCS score was 24 (18–28, 13% ≥ cutoff), pre-operative PD-Q score was 16 (8–22, 50% ≥ cutoff) and NRS score was 9.5 (8–10). Conclusions This study indicates that it is possible to implement preoperative questionnaires in a clinical setting. However, more than 50% of the patients are unable to complete the questionnaires.

Aims Optimization of pain management is essential for fasttrack surgery and safety in acute hip fracture (AHF) patients. Kidney function determines the doses of several postoperative painkillers, but previous studies have shown the standard Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation overestimate glomerular filtration rate (GFR) in elderly and underweight patients. The optimized Cockcroft Gault (CGop) equation might be more accurate in this patient group. The study aims to (1) investigate the differences in estimated GFR (eGFR) based on CKD-EPI and CGop and (2) to simulate this impact on recommended dosing of standard painkillers in AHF patients. Methods Patients admitted with AHF from January to April 2015 were included. eGFR was calculated for each patient by CKD-EPI and CGop based on the lowest measured serum creatinine between 1 and 4 days postoperatively. CKD-classification (1–5) was performed based on both eGFR values. If patients were classified differently based on the two eGFR values, then drug dosages were simulated for Morphine, Ibuprofen and Gabapentin according to prescribing recommendations in Renbase®.Two-sided Mann–Whitney test was used to compare median values between groups. Results 176 patients (62% women) with a median age of 76 years were included. CKD-EPI (78.0mL/min/m 2 ) estimated eGFR significantly higher compared with GGop (58.9, P < 0.001). Depending on the equation used to estimate GFR, CKD ≥ 3 (eGFR < 60 mL/min/m 2 ) occurred in 23–53% all patients. Using CGop to estimate GFR resulted in CKD re-classification for 63% of all patients. Using CKD-EPI to estimate GFR resulted in significantly higher doses of Morphine, Ibuprofen and Gabapentin ( P < 0.0001) in re-classified patients. Conclusions GFR estimates are significantly higher when calculated by CKD-EPI compared to CGop, and this difference results in significantly higher recommended doses of painkillers in AHF patients. Future studies should include a gold standard for measuring GFR and maybe alternative biomarkers for the renal function.

Aims Selective activation of nociceptive fibers is difficult using electrical stimulation as the activation threshold is higher than for non-nociceptive fibers. It remains unclear to what extent accommodation of non-nociceptive fibers during slowly rising electrical pulses can be utilized to reverse this activation order. The aim of this study was to evaluate the ability of different pulse forms to activate nociceptive fibers with minimal co-activation of non-nociceptive fibers by comparing subjective perception thresholds (PT). Methods Electrical pulses were applied on the volar forearm of 25 subjects with (1) small diameter pin electrodes providing high current density in the skin epidermis, where primarily nociceptive fibers terminate and (2) standard patch electrodes (2.63 cm 2 ). PTs were obtained for exponential current increase, linear current increase, increasing form of exponential current decay (ED), and standard rectangular current pulses. All pulse forms were tested at two relatively long durations (5 and 50 ms). The PT ratio between patch- and pin electrode was calculated as an estimate of the ability of a pulse form to preferentially activate nociceptive fibers. The short form McGill pain questionnaire (SF-MPQ) was used to assess perceived quality of pain for all pulse forms. Results For the pin electrode, PT tended to decrease with increasing pulse area. Patch electrode PT tended to increase for increasing pulse area for non-rectangular 50 ms pulses, in contrast to 5 ms pulses, indicating accommodation of non-nociceptive fibers. Largest PT ratio was obtained for the 50 ms ED. SF-MPQ scores were higher for the pin- compared to the patch electrode. Pin electrode pain qualities were mainly described as stabbing and sharp. SF-MPQ scores did not differ between pulse forms. Conclusions Long duration ED pulses seem to activate nociceptive fibers better than regular, short duration pulses; most likely reflecting accommodation of non-nociceptive fibers.

Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to decrease this inflammatory activity.

Aims Conditioned pain modulation (CPM) is used to assess descending pain modulation through a test stimulation (TS) and a conditioning stimulation (CS). Due to potential carry-over effects, sequential CPM paradigms might alter the intensity of the CS, which potentially can alter the CPM-effect. This study aimed to investigate the difference between a fixed and adaptive CS intensity on CPM-effect. Methods On the dominant leg of 20 healthy subjects the cuff pressure detection threshold (PDT) was recorded as TS and the pain tolerance threshold (PTT) was assessed on the non-dominant leg for estimating the CS. The difference in PDT before and during CS defined the CPM-effect. The CPM-effect was assessed four times using a CS with intensities of 70% of baseline PTT (fixed) or 70% of PTT measured throughout the session (adaptive). Pain intensity of the conditioning stimulus was assessed on a numeric rating scale (NRS). Data were analyzed with repeated-measures ANOVA. Results No difference was found comparing the four PDTs assessed before CSs for the fixed and the adaptive paradigms. The CS pressure intensity for the adaptive paradigm was increasing during the four repeated assessments ( P < 0.01). The pain intensity was similar during the fixed (NRS: 5.8±0.5) and the adjusted paradigm (NRS: 6.0±0.4). The CPM-effect was higher using the fixed condition compared with the adaptive condition ( P < 0.05). Conclusions The current study found that sequential CPM paradigms using a fixed conditioning stimulus produced an increased CPM-effect compared with adaptive and increasing conditioning intensities.

Background Gabapentin (GAB) has recently been introduced for postoperative pain treatment in orthopedic surgery. As persistent postoperative pain is still a major problem in total knee arthroplasty (TKA), studies on the effect and side effects of Gabapentin in addition to the commonly used morphine (MOR), Oxynorm (OXY) and Norspan (NOR) are highly warranted. In the present study, four relevant treatment algorithms, gabapentin and morphine (GAB/MOR), gabapentin and Oxynorm (GAB/OXY), Oxynorm (OXY) and Gabapentin, Oxynorm and Norspan (GAB/OXY/NOR) were examined. Patients and methods A total of 241 patients were followed systematically during one month following TKA in four consecutive series: 60 patients were treated with GAB/MOR, 62 patients with GAB/OXY, 59 patients with OXY, and 60 patients with GAB/OXY/MOR. On the day before surgery and on postoperative day 1, 14, and 30, pain during rest, pain during walking and side effects (constipation, dizziness, and nausea) were reported (VAS). Results After 30 days, pain greatly decreased in all groups, with a superior effect of GAB/OXY/NOR for pain during rest and only slightly more side effects at day 1. Conclusions In management of postoperative pain following TKA, data indicated that GAB/OXY/NOR was superior, compared to GAB/MOR, GAB/OXY, and OXY.

Aims Conditioned pain modulation (CPM) is a paradigm employed to assess descending control of spinal nociception. Previous studies have shown that CPM affects the nociceptive withdrawal reflex (NWR) threshold (RTh), typically assessed in one muscle. However, the NWR activates not one but a group of synergistic muscles, which are recruited by common neural commands to achieve the limb withdrawal. In this regard, synergy analysis can provide the minimum coordinated recruitment of groups of muscles with specific activation balances that describe a movement. The aim was to assess how CPM modulate the global withdrawal strategy of the lower limb expressed by synergy analysis. Methods Sixteen healthy subjects received electrical stimulation in the arch of the foot at 2 × RTh intensity assessed at the biceps femoris muscle, to elicit the NWR at three time points: before, during and after immersion of the hand in cold water at 2.6 ± 0.4° (cold pressor test, CPT) to trigger CPM. Electromyographic signals (EMG) were recorded from 2 distal muscles (tibialis anterior, soleus) and 2 proximal muscles (biceps femoris, rectus femoris). Muscle synergies were identified by a non-negative matrix factorization algorithm for the EMG envelope in the 60–180 ms post-stimulus interval. Data were analyzed by a point-by-point Wilcoxon test using a permutation strategy. Results The overall withdrawal pattern was explained by two main synergies (Syn1 and Syn2). Syn1 mainly contributes to EMG of distal muscles, whereas Syn2 contributes to EMG of proximal muscles. During CPT, the magnitude of Syn2 was reduced in the 160–180ms post-stimulus interval ( p < 0.05), whereas no changes were found for Syn1. Conclusions At least two synergies are required to explain the NWR. Furthermore, results suggest that CPM might differentially affect proximal and distal muscles. Further analysis is needed to provide additional information about the behavior of the individual muscles.

Aims Lumbar radicular pain is often associated with increased local and systemic synthesis of inflammatory mediators. This process can be modulated by specific microRNAs (miRs). Here, in the animal model, we investigated the effect of miR-223 on the spinal nociceptive signaling and local gene expression. Methods In anaesthetized Lewis rats, extracellular single unit recordings of spinal nociceptive activity and qPCR were used to explore the effect of miR-223 application onto the dorsal nerve roots (L3–L5). Results A significant decrease in the C-fiber response was observed following application of miR-223 onto the dorsal nerve roots. In addition, the gene expression of interleukin-6 (IL-6) was increased in the spinal cord. Conclusions Our data suggest that miR-223 may influence nociceptive signaling in the pain pathways, possibly by modulating the expression of inflammatory mediators.

Aims Muscle pain affects corticomotor areas representing the affected muscle, by changing the size of representation and reduces the corticospinal output as assessed by transcranial magnetic stimulation (TMS). Less work has been done to understand how pain in one muscle group may affect synergistic ipsilateral muscles distal to the pain. This study aimed to explore the effects of acute extensor carpi radialis (ECR) muscle pain on TMS motor-evoked potentials (MEPs) of the ECR and the first dorsal interosseus (FDI) muscle, which are known to strongly overlap within the corticomotor area. Methods Eight healthy volunteers (1 woman) were injected with hypertonic saline (5.8%, 0.5 mL) into the ECR muscle. Pain intensity was assessed by the visual analogue scale (VAS) every minute for 10 min. TMS was applied at 120% of ECR resting motor threshold, and MEPs were acquired from the ECR and the FDI muscles. At baseline, 10 TMS pulses were delivered. Temporal mapping of ECR and FDI MEPs over 10 min duration was performed by delivering 100 single-pulses of TMS, at 6 s interstimulus-interval. The MEPs for each muscle were averaged at baseline, peak-pain (1 –2 min epoch), and 10 min post-injection Results Pain intensity reduced significantly at 10 min postinjection as compared to peak-pain ( P = 0.011). Further, one-way repeated measures analysis of variance revealed that ECR MEPs were altered at peak-pain compared to baseline ( P > 0.05), but not 10 min post-injection ( P > 0.05). Baseline and 10 min post-injection of ECR MEPs did not differ significantly ( P = 0.67). The MEPs of the FDI muscle did not show a similar alteration over time ( P = 0.1). Conclusions Despite the overlap between ECR and FDI representations, acute muscle pain of the ECR only significantly altered cortical excitability of the ECR muscle representation.

Aims Novel quantitative thermal stimulator devices (QTSDs) have been developed to deliver thermal pulse stimulation with regulated constant temperatures (0–45°C) with a Peltier element probe (16 cm 2 ). The aim of this study was to investigate subjective sensation induced by the interaction between simultaneously applied painful cold and heat stimuli in various sites. Methods Twenty healthy subjects (12 men and 8 women, age range: 25–45 years) participated. The intensity of cold pain (CP) and heat pain (HP) stimuli were assessed by visual analogue scale (VAS) and adjusted to elicit approximately 70/100 mm. Alternately pulse stimulations (pulse duration of 40 s; 0.025 Hz) which consisted of CP, HP, or neutral temperature (32°C) were applied. Four conditions were tested and subjective sensations were assessed: (1) one QTSD was applied to non-dominant forearm and cold-heat pulse stimulation was applied. Two QTSDs were applied to (2) non-dominant ipsilateral forearm with 5 cm apart, (3) non-dominant and contralateral forearms, (4) non-dominant forearm and ipsilateral thigh, respectively. In conditions of (2)–(4), CP-neutral pulse stimulation (C-Neutral) and neutral-HP pulse stimulation (Neutral-H) were applied simultaneously with opposite phase, respectively. Results CP and HP were 3.9±1.0°C (mean±SD) and 43.6±0.9°C (mean±SD), respectively. The VAS values for CP and HP were 73.4±2.0 mm (mean±SD) and 76.4 ±4.8 mm (mean±SD), respectively. Some subjects could not discriminate cold or heat sensation and some felt cold as heat (paradoxical sensation). The number of subjects with such paradoxical sensation in (1), (2), (3), (4) were 9 (45%), 2 (10%), 0 (0%) and 3 (15%), respectively. Conclusions In healthy volunteers, simultaneous alternately cold-heat pulse stimulation on one site triggered paradoxical thermal sensation, which to a much less degree is triggered when C-Neutral and Neutral-H were applied to different dermatomes. This suggests that the mechanism is primarily triggered peripherally.

Background and aims Offset Analgesia (OA) is a disproportionally large decrease of pain perception evoked by a slight decrease of a painful cutaneous heat stimulus, resulting in a lower pain perception compared to a simple constant stimulus at the same temperature. This study aimed to investigate the possibility of evoking the same disproportional analgesic effect by applying electrical stimuli. Methods 24 subjects underwent two control-trials of 30 s constant intensity by applying either heat stimulation at 48 °C or an electrical stimulation at 150% of the individual electrical Pain Detection (ePD) on the volar forearm. OA-trials consisted of a 30 s stimulation, divided into three periods: T1 (5 s), T2 (5 s), and T3 (20 s), with stimuli intensities of 48 °C, 49°C and 48°C or 150% of ePD, 180% of ePD, and 150% of ePD. Subjects were asked to rate the pain intensity on an electronic Visual Analog Scale (VAS; 0: no pain; 10: worst imaginable pain), and were categorized as responders if they showed more than 30% lower VAS at heat OA-trials compared to heat control-trial. Repeated measures Analysis of Variance was applied to investigate the difference in pain intensity to the electrical OA-trials, compared with the electrical control-trials. Results Responders to the heat OA-trial also responded to the electrical OA-trial compared to the electrical control-trial, with an analgesic effect of 3.3±0.5 VAS points ( P < 0.001). However, when analyzing all subjects, no difference was found comparing the electrical OA-trial (VAS 3.8±0.5) to the electrical control-trial (VAS 6.2±0.4; P > 0.5). Conclusions This study suggests that responders to the heat OA-paradigm also respond to the electrical OA-paradigm.

Background Symptoms from disseminated cancer can develop very slowly. This could be very difficult to distinguish those symptoms from chronic disabilities and nuisances in patients with chronic non-malignant pain. Objective In this report, the case of a woman with both nonmalignant pain and cancer is presented. Case report A 54 years old woman was referred by a general practitioner to Multidisciplinary Pain Center. The diagnosis was chronic non-malignant neck pain on the basis of degenerative columnar disease. The patient was also suffering from osteoporosis. During the first visit in the Center, the patient complained of shooting pains in the neck and had tingling sensations in the fingers – most of his right hand. Moreover, the patient experienced shooting pains in the hips, lower back and spine. The multidisciplinary treatment with medication, physical therapy, TENS and cognitive behavioral therapy was offered. Paracetamol together with gabapentin was used. The patient experienced relief of pain. The doses of gabapentin was escalated up to 2400 mg daily without significant side effects. Afterwards, the dose was gradually increased to 3600 mg daily and the patient experienced fatigue, mild headache and dizziness. These symptoms were initially interpreted as side effects of gabapentin. However, the tingling sensations in the fingers were almost disappeared. The doses of gabapentin was reduced, but without relief of symptoms. Within 2 weeks, the patient developed partial paresis of the right upper limb and aphasia. The patient was urgently referred to the neurologic inpatient clinic. CT- and MR-scans showed multiple cerebral metastases. Under the diagnostic workup the lung tumor was found. The biopsy showed pulmonary adenocarcinoma. Conclusions The symptoms of lung cancer with cerebral metastases can mimic side effects of gabapentin.

Aims The purpose of this study was to investigate potential gender differences in pain referral patterns induced by a tonic painful mechanical stimulus. Methods Forty-five healthy adults (22 women) participated in this study. Pressure pain thresholds (PPTs) were assessed at the infraspinatus, the brachioradialis and the gastrocnemius muscles on the dominant side, using handheld algometry. Following this, painful pressure at the infraspinatus muscle was induced using the algometer by rapidly increasing the pressure until it reached the level of 7 cm on VAS (PVAS7). This pressure was kept constant for 60s. Upon release, the subject was asked to indicate the area of the pressure-induced pain on a digital body chart. PPT values, PVAS7 and the pain area (number of pixels) were extracted for data analysis. Results No gender differences were found in PPT values ( P >0.05). The pressure needed to reach 7 cm on the VAS was significantly lower in the female group (687.4±50.5 kPa) compared with males (971.0 ± 49.6 kPa; unpaired t -test: P < 0.05). The size of the pain area following PVAS7 stimulation for 60 s was significantly larger in the female group (12,578.5 ± 17,280.3 pixels) compared with the male group (6175.0 ± 9518.5 pixels; Mann–Whitney-U; P < 0.05). Conclusions Despite comparable PPT values, women demonstrated larger pain areas compared with men although the standardized painful stimulus which intensity was perceived similarly as 7 cm on the VAS scale in both groups. These findings suggest that there are gender-specific differences in pain distribution and referred pain but it is unclear through which mechanism they are mediated.

Background Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction. However, it is unknown if the inhibition can be reduced by opioid antagonism with oral naloxone, and how this compares to osmotic laxative treatment. Aims To compare the effects of oxycodone and macrogol 3350 treatment (OX + PEG) versus combined oral oxycodone and naloxone (OXN) on anal sphincter function and gastrointestinal symptoms. Methods A randomised, double-blind, crossover trial was conducted in 20 healthy, male volunteers. Participants were randomised to five days treatment of OX + PEG or OXN. Anal resting pressure, anal canal distensibility, and rectoanal inhibitory reflex-induced sphincter relaxation were evaluated at baseline and on day 5. The Patient Assessment of Constipation questionnaire (PAC-SYM), stool frequency, and stool consistency were assed daily. Results Sphincter relaxation was reduced after OX + PEG treatment compared to OXN (difference = −17.6% [95% Cl;−25.2, −10.2]; P < 0.001). Anal resting pressure and anal canal distensibility did not differ between the treatments. PAC-SYM abdominal symptom subscale increased during OX + PEG compared to OXN (cumulated score: 3.2±2.3 vs. 0.2±1.8; P =0.002). Number of bowel movements was higher during OX + PEG vs. OXN (5.4±1.5 vs. 4.2±1.2; P = 0.035), but there was no difference in stool consistency (3.5±0.5 vs. 3.2±0.4; P = 0.14). Conclusions Sphincter relaxation was significantly reduced after OX + PEG compared to OXN. Evaluation of the rectoanal inhibitory reflex may serve as an important objective measure in future trials on treatment of opioid-induced bowel dysfunction.

Aims Itch often occurs in cutaneous conditions characterized by some degree of inflammation, e.g. atopic dermatitis, psoriasis or urticaria. It is unclear to which extent cutaneous inflammation causes sensitization of pruriceptive primary afferent C-fibers. The aim of this study was to explore if inflammation induced by UVB (B-ultraviolet rays) modify neurogenic inflammation and itch associated with experimental itch provocations. Methods Twenty healthy volunteers (10F/10M, 26.2 ± 1.6 years) were included. Eight circles (diameter=2cm), four on each volar forearm were studied. Two spots were irradiated with 0.5 × Minimal Erythema Dose (MED), two with 1× MED and two with 2× MED, and two acted as controls. Itch provocations were conducted using histamine (1%) percutaneously introduced and 35–45 cowhage spicules (non-histaminergic itch). The duration and intensity of itch and pain, sensitivity to touch-evoked itch (STI), mechanical pain thresholds (MPT) and sensitivity (MPS), and superficial blood perfusion where measured in UVB-irradiated- and control areas 24-h after UVB-irradiation and following each itch provocation. Results UVB induced dose-dependent hyperalgesia validated by decreased MPT, increased MPS and neurogenic inflammation (all P < 0.01). UVB-induced inflammation did not increase the magnitude of itch reported following any itch provocation. However, cowhage was associated with more pain in UVB-irradiated areas and the proportional ratings of the mixed itch and pain sensation was shifted towards increased pain dominance ( P < 0.01). Itch provocations did not increase the mechanical hyperalgesia induced by UVB, whereas it provoked an increase in superficial blood perfusion compared to UVB alone ( P < 0.05). Conclusions (1) The UVB model induces sensitization to pain but not itch stimuli and independently increases the nociceptive sensations associated with non-histaminergic itch provocation. (2) The inflammatory UVB-perturbation does not mimic the sensitization associated with inflammatory dermatoses where lesioned skin is more receptive to pruritogens, suggesting that more specific or prolonged inflammatory processes are involved in clinical itch conditions.

Aims Transient receptor potential ion channel A1 (TRPA1) has been shown to play a pathoetiological role in several painful and inflammatory conditions and therefore several new drug candidates, targeting TRPA1 are currently being developed [1]. While the natural TRPA1-agonist allyl-isothiocyanate (AITC, known as “mustard oil”) is an exceedingly common animal pain model, it has only been sparsely investigated as a potential human surrogate model of pain and neurogenic inflammation. This study aimed to evaluate dose-response features of AITC as a sensitizing, algogenic irritant in human skin. Methods Three concentrations of AITC (10%, 50%, 90%) and vehicle (100% paraffin) were applied for 5 min to 3 cm × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain (visual analog scale 0–100 mm) and pain quality were assessed. Following the application, a battery of quantitative sensory tests was conducted including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was evaluated using Laser Perfusion Imaging (FLPI). Erythema and pigmentation were assessed before, immediately after and≈64 h after AITC exposure. Results Topical application of AITC induced significant dose-dependent, moderate-to-severe spontaneous pain mostly described as burning as well as mechanical and heat hyperalgesia ( p < 0.05). The model also produced robust dynamic mechanical allodynia ( p < 0.05). Only modest increases in pain hypersensitivity were observed between the 50% and 90% concentrations. Neurogenic inflammation was evoked by all concentrations and assessments by FLPI demonstrated a significant dose dependent increase from 10% to 50% ATIC, with a ceiling effect from 50% to 90%. Conclusions Topical AITC-application evokes dose-dependent rapid pain and somatosensory sensitization with optimal concentrations recommended to be above 10% and equal to or below 50%. The model is translatable and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics and anti-inflammatory compounds or for exploratory clinical purposes (e.g. loss- or gain-of-function in peripheral neuropathies).

Introduction Total knee replacement (TKR) is the treatment of choice for the millions of individuals whose osteoarthritis related pain can no longer be managed through non-invasive methods. Although most patients report improvement in pain and functioning following TKR, up to 30% report after 1–2 years persistent pain that interferes with their daily function. Further knowledge on long term results are highly demanded. The present study is the first 5 year follow-up of all patients from a whole region. Methods Patients were interviewed by letter concerning pain, overall satisfaction and forgotten joint score (FJS). In 2011, 607 patients in the region of North Denmark had a primary TKR, of which 20 was bilateral. Still alive are 546 patients. A total of 498 answered by letter (91%) of which 13 were not able to answer detailed due to psychological reasons. Results A total of 290 (59%) patients were very satisfied with their TKR, 140 (30%) were satisfied and 58 (12%) dissatisfied. Pain free were 269 (55%). 163 patients (33%) experienced moderate pain and 55 (11%) had strong pain . Dissatisfaction and pain were highly correlated, especially pain at walking: Among patients reporting strong pain, 35 (64%) scored higher than 6 on the VAS-average pain last 24 h versus 46 (84%) that scored higher than 6 on the VAS-pain after 30 min’s walk. Conclusions Among an unselected series of patients having TKR, 12% were dissatisfied and 11% still had strong pain 5 years later. Dissatisfaction was especially correlated with pain when walking. Thus, the association between dissatisfaction, pain at activity and the individual expectations should be further focused.

Aims Stimulus intensity used for assessing temporal summation of pain (TSP) is commonly set at the participants’ pain tolerance. Yet pain ratings during TSP rarely reach that initial pain tolerance pain rating. This study aimed to explore the differences between baseline pain tolerance assessed by cuff algometry and subsequent pain ratings of the same stimulus intensity, and the reliability of these ratings over 2 sessions. Methods In two sessions, separated by one week, 24 healthy, pain-free males had their pressure pain detection (PDT) and tolerance threshold (PTT) recorded using a staircase inflation paradigm (5 kPa increments, 1sec-ON:4sec-OFF) with a cuff algometry system. The pain intensity was assessed during cuff stimulation using an electronic visual analogue scale (VAS, 0–10 cm). Three different inflation paradigms were then performed, using the PTT level as stimulation intensity, and a 1-s duration for each stimulus: PEAKS: 3 inflations at 0.17 Hz, SLOW: 10 inflations at 0.01 Hz, FAST: 10 inflations at 0.5 Hz). Approximately 5-min was kept between the staircase assessment and the first stimulation paradigm, and between each of the 3 inflation paradigms. The PTT and first inflation VAS rating from each paradigm was extracted. Results The VAS rating of PTT pressure was higher in the staircase (VAS: 8.5±2.1 cm) than the first PPT stimulus in any other paradigm (PEAKS: 5.4±2.0; SLOW: 4.6±2.1; FAST: 4.0±2.3, P < 0.05). VAS ratings were also lower in each subsequent paradigm (i.e. PEAKS > SLOW > FAST, P < 0.05). Intra-class coefficients demonstrated excellent reliability for each paradigm (all ICC > 0.79) between sessions. Conclusions PTT, as assessed with the staircase inflation paradigm, was rated more painful during baseline assessment than when the identical stimulus profile (PPT intensity for 1-s) was applied afterwards and this finding is considered reliable.

Aims A fast-track based surgical treatment reduces morbidity and hospital stay by providing early mobilization. Sufficient postoperative pain management is mandatory for early mobilization and optimal utilization of rehabilitation measures. Insufficient postoperative pain management is however a widespread problem. Lack of knowledge about pain and pain treatment among health care professionals and general community has been considered as a major potential contributor in insufficient pain management. It has been suggested that severe postoperative pain might imply a potential risk of developing chronic pain. The purpose of this study was to examine this problem in acute and elective surgical patients in department of orthopedic surgery at Bispebjerg Hospital in order to identify obstacles and possibilities for future improvement. Methods Questionnaires were developed and distributed to patients consisted of 10 acute admitted and 10 elective orthopedic patients. The patients’ pain scores were recorded with a 0–10 NRS scale. The scores were obtained for current pain in rest, current pain in activity, and the highest and lowest pain intensity for the last 24 hours. Data were handled using descriptive statistics. Results The goal for sufficient pain treatment was patients with pain score at ≤ 3 NRS at rest and ≤ 5 in activity. For pain at rest 45% of the patients were within the goal range and 55% for the current pain in activity. For the mildest pain experienced in the last 24 h, 75% and for the worst pain experienced 30% of the patients reached the goal. Conclusions Corresponding to similar studies, half of the patients received a sufficient pain treatment at the time of examination. The consequences for insufficient pain management would be reduced effect of the physiotherapy, reduced ability to handle every day activity, sleep disturbances, and potential risk of developing chronic pain.

Aims Traditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM. Methods 20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, “0” represented “no pain”, and “10” represented “maximal pain”). The pain detection threshold (PDT) was defined as “1” on the VAS scale. Results There was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P < 0.05, 4.0 mA vs 5.1 mA; P < 0.05). Conclusions The study indicates that CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.

Background Non-Steroidal Anti-Inflammatory Drug (NSAID) treatment is recommended as the first step in the treatment of knee osteoarthritis (KOA). Due to the risk of side-effects of NSIADs and low responds rate, methods for selection of NSAID responders are highly warranted. Recent studies suggest that pain sensitization in KOA might be predictive for the effect of surgical treatment, why the purpose of the present study was to evaluated whether quantitative sensory testing (QST) could be predictive for the effect of NSAID treatment in KOA. Material and methods 100 patients were enrolled and assessed using temporal summation of pain (TSP), pressure pain thresholds (PPT) and pain intensity (visual analog scale, VAS; 0: no pain and 10: worst imaginable pain) before and 8 weeks after daily treatment of Ibuprofen 400 mg × 3, Paracetamol 1 g × 3 and Pantoprazole 20 mg × 1. TSP was assessed by the difference in pain scores to one PinPrick stimulus followed by 10 PinPrick stimuli. PPT was assessed at the extensor carpi radialis longus muscle. Responders were categorized as decrease in pain intensity of at least three VAS-points. Results 80 patients had complete data at follow-up. 28 patients were categorized as responders and 52 patients as non-responders. Pre-treatment pain intensity (responders: 7.5 (SD: 1.6) vs. nonresponders: 6.5 (SD: 2.3), P < 0.03) and TSP (responders: 1.9 (SD: 2.5) vs. non-responders: 1.0 (SD: 1.5), P < 0.05) were significantly higher in responders compared with non-responders. Pre-treatment PPT at the arm trended towards significantly lower in responders (293 kPa (SD: 85)) compared with no responders (339 kPa (SD: 124), P < 0.06). Conclusions This preliminary analysis indicate that KOA patients with high pain intensities, facilitated TSP and widespread pressure hyperalgesia respond to NSAIDs.

Background Patients with complicated chronic non-malignant pain (CCNMP) should be referred to the multidisciplinary treatment based on the biopsychosocial pain model. This is not a trivial task to obtain the biopsychosocial record (BPSR) during the first visit in multidisciplinary pain center – some important data can be missing, but it is difficult to choose the right questions. Purpose To find the optimal method for obtaining of BPSR in patients with CCNMP. Methods The action research methodology is used. First, the literature search was done. Second, the meetings between therapists were hold. Third, the patients are asked about their experiences with obtaining of BPSR. Results The following area of interest were identified: (1) patient’s demographic data, (2) lifestyle factors, (3) previous diseases, (4) concurrent diseases, (5) previous pain treatments, (6) pain intensity and effect of the actual pain treatment, (7) general activity, (8) mood, (9) walking activity, (10) work ability, (11) home activities, (12) relations with other people, (13) sleep, (14) enjoyment of life, (15) patients expectations from treatment, and (16) treatment goals. Patients are asked about those variables. Either Visual Analogue Scale or Numeric Rating Scale is used for assessment of pain intensity and pain influence on variables (7) to (14). First, data about variables (1) to (6) are collected by the physician. Next, data about variables (7) to (15) are gathered under interview with the nurse. Last, the physician and the nurse keep the meeting on treatment goals and treatment course. Up to date (February 2017), 8 patients were asked about their experience with obtaining of BPSR. All but one patient were very satisfied. Conclusions The method presented above seems to be promising approach to obtaining of BPSJ in patients with CCNMP. The study is ongoing and updated results will be presented at the conference.

Aims Evaluate pressure pain threshold (PPT) over cervical facet joints before and after injection of experimental pain in the trapezius and multifidus muscles. Methods Fourteen healthy subjects (6 women) received randomized ultrasound-guided injections of hypertonic saline (5.8%), in the right multifidus muscle medial to C4/C5 facet joint and in the right trapezius muscle at the midpoint between C7 spinous process and acromion. The saline-induced pain intensity was assessed on a VAS scale. Before and during saline-induced pain PPTs were assessed by pressure algometry bilaterally over C2/C3 and C5/C6 facet joints. Three-way repeated-measures ANOVA with factors PPT location, injection site, and time was used for analysis. Post-hoc analysis was done by Bonferroni. Results Saline-induced trapezius muscle pain increased PPTs over all facet joints ( P < 0.05) compared with before pain. Saline-induced multifidus muscle pain increased PPTs bilaterally over C2/C3 facet joints and over the left C5/C6 facet joint ( P < 0.05) compared with before pain. Conclusions Trapezius muscle pain increased PPT over assessed facet joints. Similar results were found for multifidus muscle pain except for the right C5/C6 facet joint, which was close to the injection site. Such findings may reflect descending inhibitory control acting on structures furthest away from the painful structure.

Background Placebo effects are positive treatment effects that occur because of the psycho-social context around the therapy. Such effects are well documented in pain treatment, as well as in the treatment of other common symptoms. Specialized Palliative Care focuses on the relief of pain and other symptoms in terminally ill cancer patients. Aims The aim of this study was to explore whether and/or how a Specialized Palliative Care Team might contribute to the creation of placebo effects. Methods The study was conducted as a qualitative study using a phenomenological/hermeneutic approach. A literature review was carried out to identify state-of-the-art knowledge about placebo effects. A triangulation of data collection techniques was used, including participant observations ( n = 8.6 h) and a focus group interview with 7 members of the Specialized Palliative Care Team. Observations from six cases were also included. Data was analyzed using NVivo 11.0. Findings This study identified work routines and situation of the Specialized Palliative Care Team that had a potential for eliciting placebo effects. The value of patient collaboration for the creation of placebo effects was identified by members of the Specialized Palliative Care Team. The team’s knowledge and attitudes concerning placebo reflect the confusion that exists in general in this area. Conclusions This study found several work routines, already in use by the Specialized Palliative Care Team, well known for creating placebo effects. Increased knowledge and focus on this phenomenon may benefit patients.

Aims Headache is a leading reason to seek medical care. Several subtypes of headaches have been defined, one of which is external compression headache. This headache is due to an external physical compression applied on the head. It affects approximately 4% of the general population; however, certain populations for example construction workers and military personnel with particular needs of headwear or helmet are at higher risk for development of this type of headache. Generally, external compression headache is poorly studied and there is no report on helmet-induced headache among Danish military personnel. This survey-based study was designed to investigate prevalence and pattern of helmet-induced external compression headache among these personnel. Methods Questionnaires were carefully developed and delivered to a total of 279 participants who use helmets in the Danish military service. The military of the Northern Jutland region of Denmark facilitated recruitment of study participants. Questionnaires were delivered on paper and anonymous answers were collected and used for further analysis. Data were handled using descriptive statistics. Results Up to 30% of the participants reported headache in relation to wearing the military helmet. Headache was defined as moderate intensity with pressing pain quality mostly located in front of the head. Two types of helmets in this study were different in the weight and padding of the inner part and delivered different pattern of pressure; while one evenly delivered pressure on multiple head regions, the other delivered pressure mostly on the sides and top of the head. This suggests that helmet pressure and headache location might be associated. Conclusions This study was first to demonstrate prevalence and pattern of helmet-induced headache among military personnel in North Jutland, Denmark. Findings of this study call for further attention to helmet-induced headache and strategies to minimize the burden, for example by design of appropriate helmets.

Aims Limited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions. Methods Rat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee. Results Co-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression. Conclusions AQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.

Background Knee osteoarthritis (KOA) was previously considered a degenerative joint disease due to wear and tear. After total Knee replacement (TKR) 13–38% of patients develop persistent post-operative pain. Emerging evidence has shown that the etiology of pain in KOA is multifaceted and may involve different structures including the synovial membrane, musculotendinous structures and neuronal tissue. Current preoperative assessment does not take these into account, thus the current study examines the role of preoperative synovitis on patient reported outcomes one-year post surgery. Material and methods 40 patients with end-stage KOA answered the KOOS questionnaire prior to receiving total knee replacement surgery. During the procedure synovitis was scored systematically at six sites where synovial excision biopsies were obtained. Macro scoring was based on three parameters (hypertrophy, vascularity and synovitis) on a 0–4 point scale. Micro biopsies where also graded based on three parameters (synovial hyperplasia, inflammatory infiltration and activation of synovial stroma) but on a 0–3 point scale. Patients received a follow up KOOS questionnaire one-year post surgery. Results 33 patients completed the KOOS questionnaire at follow-up. A high correlation between the micro mean, micro max, macro mean, and macro max was found. The micro mean was chosen as a proxy for the amount of synovitis. A multiple linear regression analysis, correcting for baseline values of BMI, age, smoking, point pressure thresholds (PPTs) and KOOS pain, showed that the synovitis measurement at baseline was significant for the change in KOOS pain with an effect of 22.22 ( p = 0.0498). Hence, the more synovitis at baseline, the higher the follow-up KOOS Pain was compared to baseline KOOS Pain (an improvement). The standard deviation (SD) of the synovitis measure was 0.42, hence a change of 1 SD in synovitis gave an increase of 9 in KOOS Pain at follow-up compared to at baseline. Conclusions These preliminary results indicate that the synovitis score attained during operation is positively correlated with improvement in KOOS-pain post operatively.

Aims Alteration in muscle milieu has been proposed as one of the main contributors underlying chronic musculoskeletal pain (CMP). Microdialysis (MD) provides real-time information on release of pain and metabolic biomarkers in muscle. However, insertion of MD probe causes a local tissue trauma, which may affect the tissue milieu. Whether an acute tissue trauma alter pain and metabolite biomarkers in trapezius muscle of patients with CMP is not known. Hence, this study investigated changes in muscle metabolites following MD probe insertion in patients with CMP in comparison with healthy controls. Methods Nineteen patients (11 women and 8 men; 41.4 years) with CMP and 20 pain-free volunteers (10 women and 10 men; 36.5 years) were recruited (project approval number: 2013/151- 31). Baseline pressure pain thresholds (PPT) at trapezius muscle were obtained bilaterally with a reference point at the tibialis muscle. Pain questionnaires were used for determining levels of anxiety and depression and catastrophizing impact. Interstitial samples were collected from trapezius muscles by aid of MD (20 kDa cut-off) during a period of 40 min. Collected dialysates at 2 time-points of 20 and 40 min were stored at −70 °C until analysis. Concentrations of glucose, lactate, pyruvate, glycerol, and glutamate were analyzed by ISCUSS flex . P ≤ 0.05 was considered significant. Results No potential case with respect to anxiety, depression or catastrophizing impact was found. Lower PPTs were found in CMP group ( P ≤ 0.05). Significantly lower levels of pyruvate were found in CMP group at both 20 min ( P = 0.003) and 40 min ( P = 0.006). Gender-based analysis indicated higher concentrations of glutamate in female patients with CMP. Conclusions This study was first to demonstrate metabolite alterations during trauma phase of MD in trapezius muscles of CPM compared with healthy controls. This model proved beneficial for investigating pain and metabolic biomarkers during acute phase of MD.

Aims Chronic pain is a significant clinical problem with few effective therapies. Objectives of this clinical registry are (1) to assist clinical decision-making, and (2) facilitate quality assurance and research projects to improve understanding and optimize treatment of patients with chronic pain. Methods PainData is an electronic software system developed for online data capture and clinical reporting, currently implemented in public pain clinics in Odense, Silkeborg, Aalborg, Næstved, Køge and Holbæk. The system captures patient-specific information across several bio-psychosocial domains of pain before the first consultation at the pain clinic as well as immediately after treatment, and 12 months after treatment. The registry also includes information from clinicians (e.g. pain diagnosis, and standardized pain sensitivity testing). PainData is registered as a clinical and research database with the Danish Data Protection Agency (16/39398, 14/44319). Results Since February 1st 2015 more than 3000 patients have completed questionnaires in PainData. The current completion rate at baseline is >80% and at follow-up is close to 50%. Pain-related data (e.g. pain-distribution, psychological distress and use of analgesics) from the registry will be presented on the poster. Conclusions The clinical pain registry contains data from a large cohort of consecutively referred chronic pain patients attending public pain clinics for multidisciplinary assessment and treatment. It contains detailed baseline and outcome data on a broad range of bio-psychosocial factors. The database has significant clinical relevance as it will contribute to an increased understanding of chronic pain conditions as well as contribute to substantial knowledge on how various psychological factors influence the experience of pain and disability in patients with chronic pain. In addition, early prediction of treatment efficacy and future stratification of patients with chronic pain has the potential to optimize treatment outcome. This will be of great interest to both the individual patient and to society.

Aims Visual feedback is hypothesized to play an important role in the phantom limb condition. In this study we attempt to create an illusory experimental model of phantom limb wherein this condition is simulated by removing the visual input from the upper limb in a group of intact participants. The aim of the study is to investigate the role of visual feedback on somatosensation, nociception and bodily-self perception. Methods Using a novel mixed reality (MR) system, the visual feedback of the left hand is removed in order to visually simulate a left hand amputation on 30 healthy participants (15 females). Using a within-subject design, three conditions are created: visual amputation condition (MR with no visual input); visual condition (MR with normal vision); and a baseline condition (no MR). Thermal detection and nociceptive thresholds using method of limits are measured. Proprioception of the visually amputated hand is investigated by probing the felt hand position on a proximal-distal axis from the body. Using a questionnaire the effects of the missing visual feedback on bodily self is assessed. Results There was a clear drift in proprioception of the left hand in the proximal direction between the control and visual amputation condition ( p <0.001). A decrease in cold detection was also significant between the control and visual amputation condition ( p < 0.001). Finally, questions on perceptual experiences indicated that the observed proprioceptive retraction of the visually amputated hand was also felt by the participants. Conclusions Missing visual feedback greatly influences the perception of the visually amputated arm underlining the importance of visual feedback. The observed proprioceptive retraction of the hand resembles the telescoping perceptions often reported by phantom limb patients. The novel method developed for this study, is a new tool to investigate the influence of visual feedback on the relationship of bodily-self and chronic pain.

Aims Respiratory depression is a serious life threatening condition and a known adverse event of opioids. Little is known about the use of the opioid antidote naloxon in Iceland, and the additive effects of other potentially respiratory depressive drugs administered with opioids. The aim of the study was to review the literature on drugs that may cause respiratory depression and to assess medication use in patients receiving parenteral naloxone in Landspítali University Hospital. Methods A review and analysis of drugs that can cause respiratory depression based on information from the scientific literature, medicine databases and clinical guidelines. A retrospective study was performed using data collected from the electronic medical records system of Landspítali University Hospital for all patients, 18 years and older that had parenteral naloxon administered in the years 2010–2014. Information about the type of opioid and other respiratory depressive drugs was collected and the data was further investigated in regards to age, gender, and type of service. Results The most potential drugs and drug classes that can cause respiratory depression when used concomitantly with opioids are benzodiazepines and other anxiolytics, hypnotics and sedatives, antipsychotics, antiepileptics, antihistamins and anesthetics. When use was examined ( N =138) morphine was the most frequent opioid given (49%). Concomitant use of opioids and other respiratory depressive drugs was seen in 63% of cases, and benzodiazepines were the most frequent drugs given with opioids (33%). Conclusions The concomitant use of benzodiazepines and other sedative drugs with opioids is frequent, despite the known risk of additive respiratory depression as described in the literature. Other patient risk factors such as medical condition, general health and consciousness should be considered in context with drugs used.

Aims To describe the evaluation of a serious computer game designed for patients to learn about post-operative pain management. Methods This was a usability and evaluation study. The sample consisted of 20 people, recruited from the public. The computer game was developed by an interdisciplinary team. In the game, the player controls the actions of a virtual human character who has been discharged home after surgery. The player needs to make decisions about the character’s daily activities, such as common household tasks and self-care, including pain management. The player observes how his decisions influence the character’s recovery. The usability and efficacy of the game were evaluated in one session with semi-structured interviews and questionnaires on knowledge acquisition and usability. The playing session was video recorded to assess if technical problems arose and how often the player needed assistance. Results The mean age of participants was 48 years (SD = 14), 11 were women. Participants described the usability of the game as high (range 3–5 on a 0–5 scale) and expressed satisfaction with this novel method of learning, despite some technological challenges. Ease of use was confirmed by observation. Knowledge of pain medications and pain management strategies improved after playing the game. The number of correct answers increased from 54%, before playing, to 71% after playing the game ( p = 0.001). Conclusions Playing an educational computer came has the potential to improve knowledge regarding post-operative pain management. The game was well received by participants. Serious computer games can be a useful tool in enhancing patient education. The game needs to be tested with surgical patients.

Aims When C-nociceptors are activated repeatedly using electrical stimulation at relatively low frequencies (0.125–2 Hz), their propagation velocity will decrease. This is referred to as activity-dependent slowing (ADS). The main reason why activity-dependent changes in velocity are of interest is that they can be recorded directly, using invasive methods (microneurography), in patients with chronic pain. Interestingly, in certain patients with neuropathic pain, reduced activity-dependent slowing of conduction has been observed, indicating that these axons have an increased excitability. Through a computational model, it is possible to link such velocity alterations with changes in active conductances, opening for an understanding the underlying excitability changes occurring in these patients. Methods We have developed a detailed multicompartment model of a C-nociceptor fiber. This model incorporates a wide range of voltage-gated ion channels (Na v 1.7, Na v 1.8, Na v 1.9, K dr , K A , K M , K Na and h ) which were implemented across a detailed and realistic axon morphology. Results The model predicts that the small diameter of the axon can accumulate intracellular sodium when it is repeatedly activated in a similar fashion as during single fiber microneurography. This increase of intracellular sodium concentration can shift the balance between ion channel currents, shift the membrane potential and membrane input resistance, and thereby generate activity-dependent changes of velocity, such as ADS as well as recovery cycle supernormality. Conclusions Our results thus provide insight into how activity-dependent excitability changes can be generated in C-fibers. By identifying which ion channels are contributing to activity-dependent changes of velocity this could provide insight into ion channel alterations in neuropathic pain patients.

Aims Translating preclinical drug-efficacy of analgesics from animal models to humans has proven challenging with many failures. Reasons are likely multifaceted, but lack of sufficiently rigorous study design, and phenotypical relevant animal models may be part of the explanation. Chronic pain is often associated with substantial comorbid burden, consisting of changes in affective state and cognitive impairment amongst other behavioral disturbances. Accordingly, many preclinical pain research activities have started to include assessment of comorbidity as a possible experimental outcome measure, but surprisingly, little consideration has been paid to the influence of animal-related factors to pain models. To address this essential issue, we have embarked on several comparative experiments in different pain-models, comparing Sprague Dawley’s (SD) from two different vendors with different inbred rat strains (Lewis (LEW), Fisher (F344) and Wistar Kyoto (WKY)) selected based on reported stress, depression, inflammatory and pain phenotypes. Methods Male rats were characterized in acute (hot-plate), inflammatory (Complete Freund’s Adjuvant (CFA)) and neuropathic (Spared Nerve Injury (SNI)) pain models, with dose-response to morphine (0.3–6.0 mg/kg) in hot-plate, CFA-induced hyperalgesia, and a locomotor motility-assay (LMA). Results F344 and SD’s were sensitive to morphine in hotplate and CFA (Minimum Effective Dose (MED) = 3.0 mg/kg). WKY rats developed a less robust mechanical hypersensitivity after CFA injection, and were less sensitive to morphine in both pain-tests (MED = 6.0 mg/kg). LEW rats were completely insensitive to morphine in the hot plate, in contrast to reversal of CFA-induced hyperalgesia (MED = 3.0 mg/kg). Additionally, neuropathic sensitivity developed with a later onset and less robustly in this strain after SNI. All strains tested in LMA exhibited sedative effects at 3.0 mg/kg. Conclusions Sensory phenotyping in response to acute, inflammatory and neuropathic pain, and sensitivity to morphine in these strains indicates that different pathophysiological mechanisms are engaged after injury. This could have profound implications for translating preclinical drug discovery efforts into pain-patients.

Aims The present study aims to identify the underlying mechanisms in the acute to chronic pain transition. Acute pain is a physiological response to an experience of noxious stimuli that can progress to chronic, becoming a disease. The negative consequences as personal suffering, reduction in physical function, maladaptive behaviours, reduction of productivity, make this condition a central and common problem affecting individuals and the society. After an acute damage, pain in some cases persists, being the process attributed to different causes, in particular persistent tissue and neuronal damages, central neuroplastic changes, psychosocial factors. Methods The techniques actually used to investigate acute and chronic pain offer only a partial explanation of the process and in addition, the obtained results are often far away from the possibility to lead some benefits in the clinical practice. Omics technologies could be the right way to detect biomarkers explaining these mechanisms. Our previous study examined epigenetic and pharmacogenetic aspects of acute and chronic pain in a large group of patients. Other omic approaches, such as metabolomics and glycomics, could help to (1) better identify metabolites that can serve as chronic pain development or side effects therapy biomarkers and to (2) better understand new insights involved into the pathophysiological mechanism that drives from acute to chronic pain. SNPs, DNA methylation, miRNA analyses, expression and protein assays on the identified pathway would than clarify the causative molecular mechanisms. In addition, linking these results to clinical evaluation of the central sensitization processes through algometry in nociceptive and neuropathic pain patients may reveal crucial clinical and pharmacological implications. Conclusions Our project will be implemented by omic technologies in different chronic pain patient cohorts (acute low back pain vs chronic low back pain patients and chronic postsurgical pain patients) in order to evaluate new possible pathophysiological mechanism with special focus in central sensitization.

Background Treatment of patients with chronic nonmalignant pain (CNMP) is challenging and requires a multidisciplinary effort. In a multidisciplinary pain center, patients are treated by a team of doctor, nurse, physiotherapist, psychologist and social worker. Especially in the beginning of treatment patients receive much information. Many patients and their relatives have problems with comprehending it. Objective This is an action research study aimed to find the optimal mode for to introduce patients with CNMP and their relatives to the multidisciplinary pain treatment. Method In the fall of 2016, we began to invite patients and their relatives to the introduction meeting (IM), which takes place in groups of up to 20 people, has duration of 1 hour and is led by the physiotherapist and nurse, but the physician is also present. Invited patients are able to understand written and oral Danish and are not suffering from social phobias. During IM facts about the center, treatment course and pain physiology are presenter. Immediately after IM, participants are anonymously asked about their experiences. Results Up to date (February 2017) 254 patients were invited. Invitation was rejected by 63 patients (24,8%). Question about understanding of chronic pain was answered by 108 participants (both patients and their relatives), and 103 participants declared better understanding of chronic pain after IM end before. 69 participants answered question about understanding of treatment course in the center. All but 2 participants declared after IM at their understanding was better end before. In fact, 31 (44,9%) participants estimated changes in understanding of treatment course as much significant. Conclusion The IM at the beginning of multidisciplinary therapy seems to be a promising activity for patients with CNMP referred to the multidisciplinary pain center, as well as for their relatives. Study is ongoing and updated results will be presented at the conference.

Background and Aims Acute Pain Services have been implemented initially to treat inadequate postoperative pain. This study was undertaken to prospectively review the current challenges of the APS team in an academic hospital assessing the effects of its activity on both surgical and medical pain intensity. It also define the characteristics of the patients and the risk factors influencing the multiple visits from the APS team. Method This prospective cohort study was conducted at Uppsala University Hospital (a Swedish tertiary and quaternary care hospital) during one year. All the patients referred to the APS team were enrolled. A standardized data collection template of demographic data, medical history, pain diagnosis, associated diseases, duration of treatment, number of visits by the APS team and type of treatment was employed. The primary outcomes were pain scores before, after treatment and the number of follow-ups. The patients were visited by APS at regular intervals and divided by the number of visits by APS team into several groups: group 1 (one visit and up to 2 follow ups); group 2 (3 to 4 follow-ups); group 3 (5 to 9 follow-ups); group 4 (10 to 19 follow-ups); group 5 (>20 followups). The difference between groups were analyzed with ordinal logistic regression analyses. Results Patients ( n = 730) (mean age 56±4, female 58%, men 42%) were distributed by service to medical (41%) and surgical (58%). Of these, 48% of patients reported a pain score of moderate to severe pain and 27% reported severe pain on the first assessment. On the last examination before discharge, they reported 25–30% less pain ( P = 0.002). The median NRS (numerical rating scores) decreased significantly from 9.6 (95% confidence interval, 8.7–9.9) to 6.3 (6.1–7.4) for the severe pain ( P < 0.0001), from 3.8 (3.2–4.3) to 2.4 (1.8–2.9) for the moderate pain. The odds ratio for frequent follow-ups of the patients between 18 and 85 years ( n = 609) was 2.33 (95% CI: 1.35–4.02) if the patient had a history of chronic neuropathic pain, 1.80(1.25–2.60) in case the patient had a history of chronic nociceptive pain, 2.06(1.30–3.26) if he had mental diseases, and 3.35(2.21–5.08) if he had opioid dependency at the time of consultation from APS. Strong predictors of frequent visits included female gender ( P = 0.04). Conclusions Beside the benefits of APS in reducing pain intensity, this study demonstrates that the focus of APS has been shifted from the traditional treatment of acute surgical pain to the clinical challenges of treating hospitalized patients with a high comorbidity of psychiatric diseases, opioid dependency and chronic pain. Implications The concept of an APS will ultimately be redefined according to the new clinical variables. In the light of the increasing number of patients with complex pain states and chronic pain, opioid dependency and psychiatric comorbidities it is mandatory that the interdisciplinary APS team should include other specialties besides the “classical interdisciplinary APS team”, as psychiatry, psychology, rehabilitation and physiotherapy with experience in treating chronic pain patients.

Background and purpose Pain is a common symptom associated with multiple sclerosis (MS), and has lasting effects on an individual’s functional capacity and quality of life. A wide range of prevalence rates of pain (between 23% and 90%)have been reported in MS and this is mainly due to the methodological differences amongst the studies such as variability in patient sources, method of sampling and the definition of pain used. Chronic pain in MS, defined as pain lasting for greater than 3–6 months, can have a significant impact on their biopsychosocial health, including negative impact on activities of daily living, relationships and social participation. The long-term course of MS-related pain and its impact in an Australian cohort over a 7-year period has been investigated earlier. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. The aim of this longitudinal study was to describe the impact of chronic pain, pain-related disability and carer burden in persons with MS over a 10-year period. Methods This was a prospective longitudinal study conducted at the Rehabilitation Department of Royal Melbourne Hospital (RMH), a tertiary referral hospital in Victoria and Australia. The source of participants was from the RMH MS database and contains detailed MS patient information including demographic data, diagnosis details (using McDonald’s criteria), pain characteristics. Structured face-face interviews and validated measures were used, which include the visual analogue scale (VAS); chronic pain grade (CPG); the assessment of quality of life (AQoL) and the carer strain index (CSI). The mean age of the participants ( n = 70) was 55.3 years and majority (70%) were female. Results The mean age of the participants ( n = 70) was 55.3 years and majority (70%) were female. The findings show that over time (10 years), participants report having greater bilateral bodily pain and greater description of pain as ‘worse as it could be’. Pain types were similar to 7-years follow-up but remained higher than baseline. There was a significant deterioration in quality of life in those with more severe CPG over time. Almost half of the participants 31 (44%) required care either from a private carer, institution or from a family member. Although fear of taking medications and side effects were common barriers to treatment for pain, there was an increase in the use of pharmacological treatment over time and an increase in the use of healthcare services, mainly neurologists and general practitioners. Conclusions The pain measures reported by the participants were similar to those at the 7-year follow-up except there was a greater representation of bilateral pain locations (limb, trunk and facial pain) compared to baseline and 7-year follow-up. At 10-year follow-up, more participants used medications compared tc 7-year follow-up and there was an increase in the use of health professionals at the 10-year follow-up At the 10-year follow up QoL of the participants deteriorated significantly and more participants had progressed to higher CPGIII and CPGIV. This study demonstrates that chronic pain is a significant issue over time in MS, with clinical and health implications, impact on quality of life, disability and healthcare utilization. Implications Greater awareness of chronic pain in pwMS, cognitive classifications and an interdisciplinary approach is required to improve long-term patient outcomes and well-being. Crown Copyright © 2017 Published by Elsevier B.V. on behalf of Scandinavian Association for the Studyof Pain. All rights reserved.

Background and Aims Clinicians treating paediatric chronic pain conditions understand that persistent pain, functional ability, and symptoms of depression often co-exist, yet these relationships have only been described to a limited extent by research. This paper more closely examines the relationship between symptoms of depression and subtypes of functional disability. Methods Participants included a clinical sample of children and adolescents ( N = 239) referred to a paediatric multidisciplinary pain clinic for treatment of persistent or recurrent (chronic) pain in Australia. The majority of participants were female, (76.6%), and were aged 7–17 years (mean age at the time of presentation was 13.8 years). Data from standardized instruments and interview data were collected from a clinical file audit. The Pediatric Outcomes Data Collection Instrument (PODCI) was used as a measure of functional difficulties performing activities of daily living, and the Children’s Depression Inventory (CDI) was used to measure depressive symptoms. Results High rates of depression and functional disability were observed, but were not associated with one another beyond relatively weak associations. Contrary to prior studies using different measures of physical functioning, depression symptoms were not associated with PODCI functional disability beyond a minor association with anhedonia symptoms (primarily driven by the pain/comfort subscale of the PODCI). Conclusions and Implications We argue that prior research has measured physical functional limitations in paediatric pain sufferers in a way that is heavily influenced by psychosocial factors, in particular by the symptoms of clinical depression. In contrast, using a measure of physical functioning (PODCI) less influenced by psychosocial factors suggests that the relationship between physical functioning during activities of daily living (e.g., use of upper limbs, basic gross and fine motor skills, basic mobility) and depression is weaker, despite both being heightened in this sample. Unlike other functional disability measures, the Pediatric Outcomes Data Collection Instrument (PODCI) may allow researchers to assess functional limitations somewhat independently of depression symptoms. This conclusion requires replication in further studies, but if confirmed, then the PODCI could be advocated as a useful measure to obtain a more ‘pure’ measure of functional difficulties due to pain, relatively independent of depression.

Background and aims Provocative pain responses following standardised protocols of repeated sagittal plane spinal bending have not been reported in people with chronic low back pain (CLBP). Potential differing pain responses to movement likely reflect complex sensorimotor interactions influenced by physical, psychological and neurophysiological factors. To date, it is unknown whether provocative pain responses following repeated bending are associated with different pain sensitivity and psychological profiles. Therefore the first aim of this study was to determine whether data-driven subgroups with different, clinically-important pain responses following repeated movement exist in a large CLBP cohort, specifically using a standardised protocol of repeated sagittal plane spinal bending. The second aim was to determine if the resultant pain responses following repeated movement were associated with pain and disability, pain sensitivity and psychological factors. Methods Clinically-important (≥2-points, 11-point numeric rating scale) changes in pain intensity following repeated forward/backward bending were examined. Participants with different provocative pain responses to forward and backward bending were profiled on age, sex, pain sensitivity, psychological variables, pain characteristics and disability. Results Three groups with differing provocative pain responses following repeated movements were derived: (i) no clinically-important increased pain in either direction ( n = 144, 49.0%), (ii) increased pain with repeated bending in one direction only (unidirectional, n = 112, 38.1%), (iii) increased pain with repeated bending in both directions (bidirectional, n = 38, 12.9%). After adjusting for psychological profile, age and sex, for the group with bidirectional pain provocation responses following repeated spinal bending, higher pressure and thermal pain sensitivity were demonstrated, while for the group with no increase in pain, better cognitive and affective psychological questionnaire scores were evident. However, these associations between provocative pain responses following movement and pain sensitivity and psychological profiles were weak. Conclusions Provocative pain responses following repeated movements in people with CLBP appear heterogeneous, and are weakly associated with pain sensitivity and psychological profiles. Implications To date, suboptimal outcomes in studies examining exercise interventions targeting directional, movement-based subgroups in people with CLBP may reflect limited consideration of broader multidimensional clinical profiles associated with LBP. This article describes heterogeneous provocative pain responses following repeated spinal bending, and their associated pain sensitivity and psychological profiles, in people with CLBP. These findings may help facilitate targeted management. For people with no increase in pain, the lack of pain provocation following repeated spinal bending, in combination with a favourable psychological profile, suggests this subgroup may have fewer barriers to functional rehabilitation. In contrast, those with pain provoked by both forward and backward bending may require specific interventions targeting increased pain sensitivity and negative psychological cognitions and affect, as these may be may be important barriers to functional rehabilitation.

Background/aims Athletes who choose to engage in contact sports do so with the knowledge that participation will bring pain in the form of contact with others, injury, and from exertion. Whilst athletes who play contact sports have been shown to have higher pain tolerance than those who do not, it is unclear whether this is a result of habituation over time, or as a result of individual differences at the outset. The aim was to compare pain responses over an athletic season in athletes who participated in contact sport and those who disengaged from it. Methods One hundred and two new contact athletes completed measures of cold and ischaemic pain tolerance, perceived pain intensity, pain bothersomeness, pain coping styles and attendance at the start, middle (4 months) and end (8 months) of their season. The athletes were drawn from martial arts, rugby and American football. Cluster analysis placed 47 athletes into a participating category and 55 into a non-participating cluster. Results Participating athletes had higher ischaemic pain tolerance at the start ( r = 0.27, p = 0.05), middle ( r = 0.41, p < 0.0001) and end of the season ( r = 0.57, p < 0.0001) compared to non-participating athletes. In addition participating athletes were more tolerant to cold pain at the end of the season ( r = 0.39, p < 0.0001), compared to non-participating athletes. Participating athletes also exhibited higher direct coping, catastrophized less about injury pain and also found contact pain to be less bothersome physically and psychologically compared to non-participating athletes. Participating athletes were more tolerant of ischaemic pain at the end of the season compared to the start ( r = 0.28, p = 0.04). Conversely nonparticipating athletes became significantly less tolerant to both pain stimuli by the end of the season (cold pressor; r = 0.54, p < 0.0001; ischaemia; r = 0.43, p = 0.006). Pain intensity as measured by a visual analogue scale did not change over the season for both groups. Conclusions Those who cease participation in contact sports become less pain tolerant of experimental pain, possibly a result of catastrophizing. The results suggest that athletes who commit to contact sports find pain less bothersome over time, possibly as a result of experience and learning to cope with pain. Athletes who continue to participate in contact sports have a higher pain tolerance, report less bothersomeness and have higher direct coping than those who drop out. In addition, tolerance to ischaemic pain increased over the season for participating athletes. Implications Having a low pain tolerance should not prevent athletes from taking part in contact sports, as pain becomes less bothersome in athletes who adhere to such activities. Participating in contact sports may result in maintained cold pain tolerance, increased ischaemic pain tolerance, reduced catastrophizing and better coping skills. Coaches can therefore work with athletes to develop pain coping strategies to aid adherence to contact sports.

Background and aims Interrupting ongoing activities with the intention to resume them again later is a natural response to pain. However, such interruptions might have negative consequences for the subsequent resumption and performance of the interrupted activity. Activity interruptions by pain may be more impairing than interruptions by non-painful stimuli, and also be subjectively experienced as such. These effects might be more pronounced in people high in pain catastrophizing. These hypotheses were investigated in two experiments. Methods In Experiment 1, healthy volunteers ( n = 24) performed an ongoing task requiring a sequence of joystick movements. Occasionally, they received either a painful electrocutaneous or a non-painful vibrotactile stimulus, followed by suspension of the ongoing task and temporary engagement in a different task (interruption task). After performing the interruption task for 30 s, participants resumed the ongoing task. As the ongoing task of Experiment 1 was rather simple, Experiment 2 ( n = 30) included a modified, somewhat more complex version of the task, in order to examine the effects of activity interruptions by pain. Results Participants made more errors and were slower to initiate movements (Experiment 1 & 2) and to complete movements (Experiment 2) when they resumed the ongoing task after an interruption, indicating that interruptions impaired subsequent performance. However, these impairments were not larger when the interruption was prompted by painful than by non-painful stimulation. Pain catastrophizing did not influence the results. Conclusions Results indicate that activity interruptions by pain have negative consequences for the performance of an activity upon its resumption, but not more so than interruptions by non-painful stimuli. Potential explanations and avenues for future research are discussed. Implications Interrupting ongoing activities is a common response to pain. In two experiments using a novel paradigm we showed that activity interruptions by pain impair subsequent activity resumption and performance. However, this effect seems to not be specific to pain.

Background and aims Sex differences in clinical pain severity and response to experimental pain are commonly reported, with women generally showing greater vulnerability. Affect, including state (a single rating) and stable (average daily ratings over two weeks) positive affect and negative affect has also been found to impact pain sensitivity and severity, and research suggests that affect may modulate pain differentially as a function of sex. The current study aimed to examine sex as a moderator of the relationships between affect and pain-related outcomes among participants with knee osteoarthritis (KOA). Methods One hundred and seventy-nine participants (59 men) with KOA completed electronic diaries assessing clinical pain, positive affect, and negative affect. A subset of participants ( n = 120) underwent quantitative sensory testing, from which a single index of central sensitization to pain was derived. We used multiple regression models to test for the interactive effects of sex and affect (positive versus negative and stable versus state) on pain-related outcomes. We used mixed effects models to test for the moderating effects of sex on the relationships between state affect and pain over time. Results Sex differences in affect and pain were identified, with men reporting significantly higher stable positive affect and lower central sensitization to pain indexed by quantitative sensory testing, as well as marginally lower KOA-specific clinical pain compared to women. Moreover, there was an interaction between stable positive affect and sex on KOA-specific clinical pain and average daily non-specific pain ratings. Post hoc analyses revealed that men showed trends towards an inverse relationship between stable positive affect and pain outcomes, while women showed no relationship between positive affect and pain. There was also a significant interaction between sex and stable negative affect and sex on KOA-specific pain such that men showed a significantly stronger positive relationship between stable negative affect and KOA-specific pain than women. Sex did not interact with state affect on pain outcomes. Conclusions Findings suggest that men may be particularly sensitive to the effects of stable positive affect and negative affect on clinical pain. Future work with larger samples is needed in order to identify potential mechanisms driving the sex-specific effects of affect on pain. Implications The current study provides novel data that suggesting that the association of positive affect, negative affect, and pain are different in men versus women with KOA. Further understanding of the difference in affective expression between men and women may lead to the development of novel therapeutic interventions and help to identify additional modifiable factors in the prevention and management of pain.

Background and aims Knowledge, attitudes and beliefs towards low back pain (LBP) can significantly impact a health care provider’s clinical decision making. Several studies have investigated interventions designed to change practitioner attitudes and beliefs towards LBP, however no such studies involving medical students have been identified. Methods This study explored medical students ‚ knowledge, attitudes and beliefs towards LBP before and after a brief educational intervention on LBP. Responses from medical students ( n = 93) were evaluated before and after a 15-min educational video on back pain. The intervention was developed using Camtasia™ video editor and screen recorder. Knowledge, attitudes and beliefs were measured using the “Modified Back Beliefs Questionnaire”, with items from two previously reported questionnaires on back beliefs. The questionnaire asks participants to indicate their agreement with statements about LBP on a 5-point Likert scale. Preferred responses were based on guidelines for the evidence-based management of LBP. The primary analysis evaluated total score on the nine-inevitability items of the Back Beliefs Questionnaire (“inevitability score”). Results Following the brief intervention there was a significant improvement in the inevitability score (post-workshop mean [SD] 20.8 [4.9] vs pre-workshop mean [SD] 26.9 [4.2]; mean difference (MD) 6.1, p < 0.001; lower score more favourable 1) and large improvements in the proportion of students providing correct responses to items on activity (pre: 49% vs post: 79%), bed rest (41% vs 75%), imaging (44% vs 74%) and recovery (25% vs 66%). Conclusions After watching the educational video students’ knowledge, beliefs and attitudes towards LBP improved and thus aligned more closely with evidence-based guidelines. Implications Medical doctors are at the forefront of managing low back pain in the community, however there is a need to strengthen musculoskeletal education in medical training programmes. The results from this research suggest educational interventions on back pain do not need to be extensive in order to have favourable outcomes on medical students’ knowledge, attitudes and beliefs towards back pain. The translational effects of these changes into clinical practice are not known.

Background and aim Pain is common and adds to the global burden of disease. However, individuals suffering from pain are a heterogeneous group in terms of pain spreading, intensity and duration. While pain influences overall health care consultation not everyone with pain consult health care. To be able to provide health care matching the patients’ needs increased knowledge about what factors determines the decision to consult health care is essential. The aim of this study was to explore the combined importance of pain spreading, intensity, duration and pain catastrophizing for consulting health care. Methods In this cross-sectional study we used population based survey data from southeast Sweden (SWEPAIN) including 7792 individuals’ aged 16–85 reporting pain. We used Modified Poisson regressions to analyse factors of importance related to the decision to consult health care. Results High and moderate pain intensity, as compared to low, increases the probability of consulting health care (High PR = 1.7 [95% CI 1.51–1.88], moderate PR = 1.2 [1.15–1.41]). Having widespread pain, as compared to localised pain, increased the probability of consulting health (PR = 1.2 [1.03–1.36). Pain duration was not associated with increased probability of consulting health care (PR = 1.0 CI0.88–1.07). However an interaction ( p = 0.05) between pain duration and pain catastrophizing beliefs was seen indicating a combined importance of the two when consulting health care. Conclusion Our result suggests that pain intensity, pain spreading and pain catastrophizing independently influence the decision to consult health care while there is an interaction effect between pain duration and pain catastrophizing beliefs where the importance of pain catastrophizing believes differ with pain duration; the importance of pain catastrophizing believes differ with pain duration. Implications Treatment and rehabilitation strategies should incorporate this finding in order to meet the individual’s needs focusing on the biopsychosocial model within health care focusing not only on actual pain reliefs but also on for example acceptance and behavioural changes.

Background and aims Pain is not merely an isolated experience occurring within the person. It takes place in a wider social context, including the immediate social relationships that the person is a part of. The aim of this paper is to provide an overview of how intercouple interactions might influence pain coping in couples coping with chronic pain. Methods Four different approaches to understanding the influence of intercouple interactions have been proposed in the literature. In this review, we present and discuss the empirical support for each of these models. A literature search on all studies published up until May 2017 (PubMed and PsycINFO) was performed. The search string consisted of 3 steps: Chronic pain AND couple interaction*/partner validation/marital interaction/chronic pain couple*/spouse response* AND coping/adjustment/disability/function/work participation/sick leave/sickness absence/work disability. Results The operant model views partner responses from the perspective of conditioned learning and focuses on how such responses might increase or decrease the occurrence of pain behaviour. The notion that partner responses can reinforce pain behaviour generally finds support in the literature. However, when it comes to negative partner responses results are mixed, and the model paints a limited picture of the range of interactions that takes place in a couple. The communal coping model focuses on one specific type of coping (i.e. catastrophizing), and emphasizes the interpersonal aspect of pain coping. There is some evidence that a tendency to catastrophize is related both to couple interactions and pain coping, but it has proved difficult to test this model empirically. The interpersonal process model of intimacy is concerned with patient disclosures of distress and subsequent validating and invalidating partner responses. There is some preliminary support that such mechanisms of validation and invalidation can be linked to pain coping. A dyadic approach focuses on processes where the couple negotiates a shared meaning of events and participates in mutual coping of a shared stressor. This approach has not been investigated explicitly, but preliminary support can be derived from studies conducted within other frameworks. Conclusions Each of the four approaches find some support in the research literature, yet none of them can explain the full range of couple interactions. We argue that the different approaches are complementary and that several of the approaches can be integrated in a dyadic understanding of pain coping. Implications All the models indicate that couple interactions can affect pain coping and that this should be taken into account when developing treatment programmes for chronic pain patients.