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Background and aims The symptoms of pain and depression often present concomitantly, but little is known as to how the different subtypes of depression affect surgical outcome. The aim of this study was to determine whether there is a difference in outcome after lumbar spine surgery between non-depressed patients and patients with different subtypes of depressive symptoms: non-melancholic (NmDS) and melancholic depression (MDS). Methods This was a cross-sectional postal survey. A self-made questionnaire, the Beck Depression Inventory (BDI) and the Oswestery Low Back Disability Questionnaire (ODI) were sent to patients who had undergone lumbar spine surgery in the Oulu University Hospital between June, 2005 and May, 2008. BDI ≤ 10 were further classified into NmDS or MDS. Results A total of 537 patients (66%) completed the survey. Of these, 361 (67%) underwent disc surgery, 85 (16%) stabilizing surgery and 91 (17%) decompression. Participants were divided into three groups: BDI< 10 N =324 (60%), NmDS N =153 (29%) and MDS N =60 (11%). The mean ODI (SD) in the BDI<1 0 group was 16 (15), in the NmDS group 36 (15), and in the MDS group 41 (18) ( p <0.001). The ODI profiles were different between the groups ( p <0.001). Pain was more frequent in depressive patients (88% of MDS, 81% in NmDS and 40% in BDI < 10 patients experienced pain, p <0.001). The intensity of pain and pain-related disability was lowest among the patients in the BDI <10 group and highest among the MDS patients. Regular pain medication was used by 87% of patients in the MDS group, 93% of patients in the NmDS group, and 71% of patients in the BDI< 10 group ( p <0.001). Response to pain medication with NRS (0–10) was 5.6 among MDS, 5.8 among NmDS and 6.5 among BDI< 10 patients ( p <0.001). Conclusion Different types of depressive symptoms are associated with poor outcome after lumbar spine surgery. The outcome was worst in patients suffering from the MDS subtype. This was observed in pain intensity, functional disability and response to pain medication. Implication It would be important to evaluate depression pre- and postoperatively. Offering a tailored rehabilitation programme to MDS patients should be considered. © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Introduction Poorly defined musculoskeletal disorders are a common clinical problem and have considerable psychosocial impact. Chronic compartment syndrome (CCS) of the legs has primarily been noted in young athletes and soldiers. The epidemiology of CCS in the general population has not been studied previously. The aim of this study was to establish the prevalence of CCS of the legs in the general population and to study its association with possible etiological factors. Methods A two-stage population survey was performed, using a questionnaire followed by clinical examination. A sample of 3000 individuals aged 25-75 years was randomly selected from the general population. A clinical examination was offered to those answering “Yes” to the following question: “Do you wake up at nights due to leg pains or cramps, causing you to walk around?” Intracompartmental pressures in the leg were measured in 13 persons randomly selected from among those diagnosed with CCS after the clinical examination. Results Of the 3000 persons contacted, 2308 (76.9%) responders were included in the study. Leg pain or cramps at night was reported by 24% of the respondents. Age, rheumatic disease, use of hormone medication, heart failure, leg oedema, and peripheral arterial disease were all significantly associated with leg pain or cramps ( P < 0.05). Among 286 persons with leg pain who underwent a subsequent clinical examination, 91 persons (31.9%) were classified as definite CCS. This suggests a CCS prevalence of 7.6% in the total sample ([24% x 31.9%/100]). In 13 of the individuals with CCS intracompartmental pressure was measured before and after performance of the step test exercise. One individual had a post-exercise pressure >15 mmHg. None had post-exercise pressure past the conventional threshold of >30 mmHg. Conclusion Nocturnal leg pain or cramps is a common symptom. A significant part of the general population (7.6%) may have CCS of the legs, with symptoms ranging from very mild to severe. Implications Considering the high prevalence of CCS found in this study, it is likely that a large proportion of those presenting with muscular pain actually have CCS. These persons are usually advised to increase their physical training to achieve some degree of pain relief. However, CCS patients may instead experience both increased leg pain and a proximal myalgia, which is possibly a referred pain. A demanding “gold standard” test (requiring identification of elevated of intracompartmental pressures), unclear diagnostic criteria, poor long-term results from incomplete surgery, and an uncertain explanation for what may be termed referred pain seem to have delayed the acceptance of CCS as a common cause of leg pain/cramps and numbness. At the same time, the enormous costs to society and the reduced quality of life of patients require that such disease entities are correctly diagnosed as they can be effectively treated by simple, low-risk surgical procedures.

Background and aims Despite improvements in surgical technique, 5%-8% of patients undergoing herniorrhaphy still suffer from clinically relevant persistent postherniotomy pain. This is a problem at both individual and society levels. The aim of this study was to determine whether or not a single nucleotide polymorphism in a specific gene contributes to the development of persistent pain after surgery. Methods One hundred individuals with persistent postherniotomy pain, along with 100 without pain matched for age, gender and type of surgery were identified in a previous cohort study on patients operated for groin hernia. All patients underwent a thorough sensory examination and blood samples were collected. DNA was extracted and analysed for single nucleotide polymorphism in the Mu opioid receptor, TNF-α, GRIK3, GCH1, BDNF and CACNA2D2 genes. Results Patients with neuropathic pain were found to have a homozygous single nucleotide polymorph in the TNF-α gene significantly more often than pain-free patients ( P =0.036, one-tailed test). Conclusions SNP in the TNF-α gene has a significant impact on the risk for developing PPSP. Implications The result suggests the involvement of genetic variance in the development of pain and this requires further investigation.

Background and aims Persistent postoperative pain (PPP) is a significant clinical problem. Several patient-related risk factors for PPP have been identified, including a previous chronic pain problem, young age, female gender and psychological vulnerability. Intra- and postoperative risk factors include surgical complications such as infections, haematoma, nerve damage and repeated surgery. As the length of hospital stay has been shortened, some patients may be discharged despite ongoing pain and insufficient analgesic medication. The challenge is to identify patients at high risk of developing PPP and to create a targeted care pathway to ensure effective and safe pain treatment especially in the subacute postoperative phase at home. This observational study describes the first two years of the Acute Pain Service Out-Patient Clinic (APS-OPC) at the Helsinki University Hospital. Methods Patient characteristics, known risk factors, and details of treatment of PPP for the first 200 patients referred to our APS-OPC were retrospectively collected from the medical records. The APS-OPC clinic functions in close collaboration with the Multidisciplinary Pain Clinic (MPC), and the number of patients in need of physiotherapist, psychologist or psychiatrist counselling was recorded, as well as the number of patients referred to the MPC for further PPP management. Results Patients were referred to the APS-OPC from different surgical specialities, the two most common being thoracic and orthopaedic surgery. Seventy per cent of the patients (139/200) presented symptoms indicating neuropathic postsurgical pain. The patients had, on average, five risk factors for PPP. The median time from surgery to the first contact to the APS-OPC was two months, and the median duration of follow-up was 2.8 months (0–16 months). The median number of contacts with APS-OPC was 3 (range 1–14). Every fourth patient needed only one contact to the APS-OPC. Nineteen per cent of the patients had an appointment with the physiotherapist and 20% with a psychologist or psychiatrist. At discharge after surgery, 54% of the patients were using weak opioids, 32% strong opioids and 71% gabapentinoids; at discharge from the APS-OPC, these numbers were 20%, 6% and 43%, respectively. Twenty-two per cent of the patients were referred to the MPC for further pain management. Conclusions The APS-OPC provides a fluent fast-track method of ensuring effective multimodal analgesia in the subacute recovery phase after surgery. Even strong opioids can be safely used after discharge and then tapered off in close supervision of the APS-OPC anaesthesiologist. As the APS-OPC was implemented in close collaboration with the MPC, the multidisciplinary resources are easily available during the course of the APS-OPC treatment. Implications The first two years of the APS-OPC have shown that a significant number of surgical patients benefit from continuing active pain management after discharge from hospital. This fast-track service provides physician-supervised titration of analgesics to improve pain relief in the subacute phase. An important task of the APS-OPC is to ensure that strong opioids are not inappropriately continued after recovery. Another goal of the APS-OPC is to identify patients in need of multidisciplinary pain management services to prevent chronification.

Background/aims Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Methods Study 1 employed a 2 (optimism vs. no-optimism) × 2 (pain vs. no-pain) × 2 (pre-score vs. postscore) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism) × 2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counterbalanced order). Continuous heat stimulation was used with temperatures oscillating around 1 °C above and 1 °C below the individual pain threshold. Results In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found that optimism protected against this pain-induced performance deterioration. Conclusions Experimentally induced pain impairs concurrent but not subsequent working memory task performance. Manipulated optimism did not counteract pain-induced deterioration of 2-back performance. Implications It is important to explore factors that may diminish the negative impact of pain on the ability to function in daily life, as pain itself often cannot be remediated. We are planning to conduct future studies that should shed further light on the conditions, contexts and executive operations for which optimism can act as a protective factor.

Graphical Abstract Abstract Background The majority of patients suffering from a whiplash injury will recover, but some will have symptoms (Whiplash Associated Disorders, WAD) for years despite conservative treatment. Some of these patients perceive neck pain that might come from a motion segment, possibly the disc. In comprehensive reviews no evidence has been found that fusion operations have a positive treatment effect on neck pain in WAD patients. Purpose Our aim was to evaluate the possibility of (a) selecting a subgroup of chronic WAD patients based on specified symptoms possibly indicating segmental pain, and (b) treating said segmental pain through fusion operation based on non-radiological segment localization. The hypothesis was that fusion operation in this selected subgroup of chronic WAD patients could alleviate perceived neck pain. Methods Eligible patients for the study had a traffic accident as the origin for their neck pain, and no previous neck symptoms. Neck pain should be the predominant symptom and the pain origin reported to be in the midline, being dull, aching in character and at sudden movements combined by a stabbing pain in the same area. Forty-nine patients with these specified symptoms were identified among a large number of chronic WAD patients. Those selected had pronounced symptoms for a median of around 50 months and had previously been investigated and fully treated within the ordinary healthcare system without success. No neurological abnormalities were to be found at clinical examination and no specific changes to be seen on X-ray and MRI. The patients were randomized to either cervical fusion operation or multimodal rehabilitation. By using a mechanical provocation test the level/s to be fused were identified. In all but one patient the surgery was performed anteriorly using microsurgical technique and a right-sided Smith-Pedersen approach and plate fixation. The multimodal rehabilitation at the Clinic of Medical Rehabilitation, Karolinska Hospital, Stockholm, included outpatient treatment for four days a week for six weeks and included treatment by physician, physiotherapists, occupational therapist, psychologists, social-service worker and nurses. Perceived change in neck pain was assessed using the Balanced Inventory for Spinal Disorders questionnaire at the 2-year-follow-up. Results Mean age of the patients was 38 and 40 years (surgery and rehabilitation groups, respectively), the most common type of accident being rear-end collision. At clinical examination muscle tenderness was not an outstanding sign. In most patients the mid-cervical region appeared to be the painful area but one patient localized the pain to C1. At follow-up 67% of the patients in the surgery group and 23% in the rehabilitation group assessed improvements in the ITT analysis. Corresponding proportions in the per protocol analysis were 83% and 12%, respectively. Conclusions The results support the supposition that among patients with central neck pain for long periods of time following a whiplash injury there are some in whom the neck pain emanates from a motion segment, probably the disc, a situation suitable for fusion surgery. Implications Thorough individual symptom evaluation in patients with chronic WAD may identify patients who will benefit from cervical fusion surgery.

Background and aims Chronic pain problems are related to specific pain related fears and maladaptive pain-coping but also commonly co-occur with other anxiety problems. Shared emotional vulnerability factors may explain this comorbidity and may influence treatment outcome. Indeed, pain patients going through multimodal pain treatment are a heterogeneous group and treatment results vary. One understudied anxiety disorder co-occurring with pain is social anxiety. This may be relevant as many pain-related challenges are situated in social contexts. The aim of this study is to investigate the occurrence of subgroups with differential patterns of social anxiety and pain related fear in a sample of chronic pain patients who receive multimodal pain treatment. The aim is also to study the characteristics of these potential subgroups and the consequences of different patterns of social anxiety and pain related fear. Methods 180 patients with chronic musculoskeletal pain answered questionnaires before and after a multimodal pain treatment in a hospital rehabilitation setting in middle Sweden. A cluster analysis using pre-treatment scores on the Social Phobia Screening Questionnaire and the Tampa Scale of Kinesiophobia was performed. Subgroups were thereafter validated and compared on impairment due to social anxiety, pain catastrophizing, anxiety, and depression. Moreover, subgroups were described and compared on vulnerability factors (anxiety sensitivity, negative affect) and outcome factors (pain intensity, pain interference, and return to work self-efficacy). Results Four distinct clusters emerged: (1) low scores, (2) pain-related fear only, (3) social concern only, and (4) high social anxiety and pain-related fear. Patients high on social anxiety and pain-related fear had significantly higher levels of anxiety sensitivity, negative affect, and higher general emotional symptomatology. They also had remaining problems posttreatment. Conclusions A subgroup of patients with clinical levels of social anxiety has suboptimal rehabilitation results, with residual emotional problems and high levels of emotional vulnerability. Implications These patients may be in need of additional treatment efforts that are not being met today. To prevent insufficient treatment results and prolonged work disability, these patients need to be detected during screening and may benefit from pain treatment that takes their emotional problems into account.

Background and purpose Isometric activation (ISOM) of deep multifidi muscles (MF) can influence postural adjustments and primary motor cortex (M1) function in chronic low back pain (CLBP). In order to better understand how ISOM impacts on CLBP condition, the present study contrasted ISOM aftereffects on Ml function, MF postural activation and pain with another training, the global activation of paravertebral muscles (GLOB, hip extension). The main objective of this study was to compare the effects of ISOM and GLOB (3-week training each) on MF postural activation and Ml function in a CLBP population. Methods Twenty-four people with CLBP were randomly allocated to ISOM and GLOB groups for a 3- week daily practice. Pre/post-training after-effects were assessed by the onset of superficial MF (MF-S) activation during ballistic limb movements (bilateral shoulder flexion in standing; unilateral hip extension in prine lying), MF-S corticomotor control tested by transcranial magnetic stimulation of M1, and assessment of pain, kinesiophobia and disability by standardized questionnaires. Results Both ISOM and GLOB improved pain and disability. However, only ISOM influenced Ml function (decreased corticospinal excitability and increased intracortical inhibition), fastened MF-S postural activation and decreased kinesiophobia. Conclusions Changes of corticospinal excitability and of MF-S postural adjustments suggest that ISOM better influenced brain plasticity. Future studies should further test whether our novel findings relate to an influence of the exercises on the lumbopelvic control of different muscles and on cognitive function. Clinically, individual’s evaluation remains warranted before prescribing one or the other of these two conventional exercises for reducing pain. Implications This original study presents how motor control exercises can influence brain plasticity and postural control in chronic low back pain. This knowledge will impact on the decision of clinicians to prescribe specific exercises with a view of improving motor control in this musculoskeletal condition.

Background and aims Pulsed radiofrequency is a non-neurodestructive invasive pain treatment which, in contrast to conventional continuous radiofrequency treatment, does not entail nerve tissue destruction. The aim of this study was to retrospectively analyse the short-term benefits of a broad use of pulsed radiofrequency in clinical practice. Methods The medical records of all patients treated with pulsed radiofrequency, or who received a diagnostic test block with a local anaesthetic in view of such a treatment, were retrospectively analysed. The patients had been referred to a tertiary pain centre in Sweden. The treatment effect one month after pulsed radiofrequency was retrospectively graded as follows, based on the wordings of the medical records: major improvement; minor improvement; no change; or worsened. Results A total of 238 patients received 587 interventions from 2009 to 2014. Chronic low back pain (CLBP) was by far the most common treatment indication (57 % of patients), followed by CLBP with sciatica (9%). The age at first pulsed radiofrequency was 55 (15-94) years (mean, range), and 65% were female. Thirty-six patients (15%) underwent only a diagnostic test block using a local anaesthetic, i.e., the test block did not lead to treatment with pulsed radiofrequency. A total of 445 pulsed radiofrequency interventions were performed on 202 patients. Dichotomizing data into responders (i.e., minor or major improvement) and non-responders (i.e., worsened or no change), we found that, out of 63 responders to a median branch diagnostic test block (either at the cervical or lumbar level), 33 were responders to the first following median branch pulsed radiofrequency. Hence the positive predictive value of a median branch test block was 52.% In 127 patients, the lumbar level was targeted for median branch pulsed radiofrequency because of clinically suspected lumbar facetogenic pain. Looking at the first treatment, 30% experienced major improvement after 1 month, 16% minor improvement, 36% no change, 5% a worsened situation, and the effect was not assessable in 13% of patients. Lone dorsal root ganglion L2-treatment for suspected discogenic lumbar pain was done on 39 patients and, after one month, the effect was not assessable in 17% of patients, 14% had major improvement, 14% minor improvement, and 55% had no change. In 40 patients, a dorsal root ganglion or a peripheral nerve was targeted because of a non-axial chronic pain condition. There was a plethora of indications, but the most common was by far related to some form of neuropathic pain (52% of interventions, mainly because of neuralgia), followed by chronic nociceptive shoulder pain (8% of interventions). Conclusions This study shows that, after one month, the effect size of a broad and indiscriminate clinical use of pulsed radiofrequency is rather small. Implications The clinical effectiveness of pulsed radiofrequency has to be investigated further in carefully selected and more homogenous patient groups, in order to define effective treatment niches for this nondestructive invasive treatment method.

Graphical Abstract Abstract Objectives The majority of patients experience moderate-to-intense pain following ankle surgery. Early, adequate treatment of postoperative pain is desirable for optimal pain relief, which in turn may facilitate optimal pulmonary function, normal respiration pattern, rehabilitation and prevention of a chronic pain condition. In this retrospective study, we aimed to identify possible predictors of moderate-to-intense postoperative pain while in the Post Anaesthesia Care Unit (PACU) in patients operated for ankle fractures. Materials and methods Social demographics and clinical characteristics from admission throughout the stay in the PACU were collected from the hospital patient record system in retrospect. Pain was assessed using a Visual Analogue Scale (VAS) or a verbal Numeric Rating Scale (vNRS). A VAS/vNRS score 4–6 was classified as moderate and 7–10 as intense pain. Other factors which were investigated were time from ankle fracture to surgery, anaesthetic procedure, pre-, per- and postoperative medical treatment, radiological classification, complexity of fracture, operative technique, and time using tourniquet procedure. Results Data from 336 patients who underwent surgery to repair an ankle fracture between January 2009 and December 2010 were analysed. None of the following variables had a statistically significant effect on pain; age, weight, smoking, timeframe from fracture to operation, type of anaesthesia, opioids given peroperatively, complexity of the fracture, operation technique or tourniquet inflation procedure. Female sex predicted moderate-to-intense postoperative pain in the PACU with odds ratio 2.31 (95% confidence interval 1.39–3.86), P = 0.001. As far as we know, this is the first study to show a sex difference in reporting pain in the first hours after surgery for ankle fracture. Conclusion Female patients operated for ankle fracture report higher pain-intensity-score than male patients while in the PACU. Implications Our findings suggest that treatment strategies to prevent high peaks of pain should particularly target women operated for an ankle fracture.

Background Young people seem increasingly disabled due to pain and stress. Pain and stress are health risks with adverse long-term health effects. Traditionally, these health risks have been most prevalent and strongest associated in females, also regarding children and adolescents. Main objectives in this study were to investigate current gender differences in musculoskeletal pain and perceived stress in adolescents aged 15 and 16 years with respect to prevalence and group differences for various aspects of stress and pain, and to explore the relationship between stress and pain, specified for gender. Methods A cross-sectional study was conducted with 17 participating public schools. The survey was administrated by the schools in accordance with given procedures, emphasizing the volunteer and anonymous participation of the pupils. Primary study measurements were pain and stress. The pain measurements addressed different aspects of musculoskeletal pain including pain sites, pain duration and pain intensity (measured by a Visual analogue scale; VAS). The stress instrument used was the Perceived stress questionnaire (PSQ) comprising different factors of stress, i.e. worries, tension, joy and demands. The secondary study measurement was body mass index (BMI). Results The study sample comprised 422 adolescents aged 15 and 16 years; 218 females and 204 males. The pain reporting was high in both genders, 57.3 per cent of the females and 44.6 per cent of the males. In general, the female adolescents reported more pain and stress, although several pain measures corresponded between genders. The pain prevalence was similar across genders with respect to lower extremity pain, back pain and arm pain. Lower extremity pain was the most frequent reported pain in both genders. More females reported head pain (Pearson Chi-Square 7.11, p = .008), severe pain (VAS ≥ 7, Pearson Chi-Square 13.12, p = .004) and moderate to severe stress (PSQ ≥ 0.45, Pearson Chi-Square 29.11, p < .001). Comparison analyses of the continuous pain and stress variables revealed significant mean (95% confidence interval [CI]) differences between genders for all stress variables with the highest mean scores in females. In both genders there were significant (p < .01) correlations between all the continuous pain and stress variables. In 9 out of 15 correlations, the stress-pain associations were strongest in males (Pearson product-moment correlation ( r ) between 0.34 and 0.38). Only in females, the body mass index (BMI) appeared associated (weakly) to pain and stress, in terms of pain intensity (VAS, r = 0.19) and lack of joy (as a factor of stress, r = 0.16). Conclusion Pain and stress were prevalent in the adolescent sample, with generally higher reporting among females. Several pain measures corresponded between genders, but stress differed significantly between genders for all variables. Scrutinizing the relationship between pain and stress revealed significant stress-pain associations regarding all variables across genders, i.e. the pain complaints among the adolescents seemed equally related to stress in males and females in the sample.

Background The Brief Pain Inventory (BPI-SF) is a widely-used generic pain interference scale, however its factor structure remains unclear. An expanded 10-item version of the Interference subscale has been proposed, but the additional value of the 3 extra items has not been rigorously evaluated. The purpose of this study was to evaluate and contrast the factorial and concurrent validity of the original 7-item and 10-item versions of the BPI-SF in a large heterogeneous sample of patients with chronic pain. Methods Exploratory and confirmatory factor analyses were conducted on independent subsets of the sample, and concurrent correlations with scales capturing similar constructs were evaluated. Results Two independent exploratory factor analyses (n = 500 each) supported a single interference factor in both the 7- and 10-item versions, while confirmatory factor analysis ( N =1000) suggested that a 2-factor structure (Physical and Affective) provided better fit. A 3-factor model, where sleep interference was the third factor, improved in model fit further. There was no significant difference in model fit between the 7- and 10-item versions. Concurrent associations with measures of general health, pain intensity and pain-related cognitions were all in the anticipated direction and magnitude and were not different by version of the BPI-SF. Conclusions and implications The addition of 3 extra items to the original 7-item Interference subscale of the BPI-SF did not improve psychometric properties. The combined results lead us to endorse a 3-factor structure (Physical, Affective, and Sleep Interference) as the more statistically and conceptually sound option.

Aims Prevalence of Sickle Cell Disease (SCD) is high in Ghana but not much is known in terms of research into non-medical strategies for managing and coping with the pain associated with SCD. This study was carried out to examine effective non-medical related strategies patients use to cope and manage their SCD condition. Methods SCD patients (387) at the Korle-bu Teaching Hospital (Sickle Cell Clinic), consisting of 180 males and 204 females between 18 and 65 years old years participated in the study. A cross-sectional research design was used in which participants completed 9 questionnaires on pain, non-medical coping and management strategies, anxiety, and depression. Results Over 90% of participants reported that pains associated with SCD were the main reason for seeking treatment in SCD crisis. In terms of non-medical related coping strategies, attending a place of worship and praying were the main coping strategies used in SCD crises, suggesting that patients’ beliefs, particularly in a supernatural being, served as a mitigating factor in the process of coping with the pain associated with SCD crisis. Also, avoidance and withdrawal from people and social activities were reported to be strategies used to cope with the pain associated with SCD crisis. Results of multiple regression analysis showed that socio-demographic characteristics contributed to the variance in the pain associated with SCD. Conclusion This study indicates that non-medical strategies, such as religious beliefs and psychosocial actions, are important factors for patients in Ghana for their coping and management of the pains associated with SCD. This knowledge may add to the understanding of the SCD-patients’ situation.

Aims To establish a network for research and education and to provide expert knowledge to parents and health care professionals about pain in early life. Methods In November 2014 a group of Nordic researchers and research students, committed to the field of pain in early life, gathered for an open lecture day and workshop in Örebro, Sweden. Inspired by the work of the Canadian initiative PICH – Pain In Child Health, the network formulated it’s vision: To be a stabile and competent research and training network within the area of pain in early life. A first collaborate project was designed: “Translation, cultural adaptation and validation of the revised version of the Premature Infant Pain Profile (PIPP-R): An effort to improve pain assessment in infants in the Nordic countries”. Results Fourteen months later, in January 2016, the second PEARL-meeting was held, in Oslo, Norway. The lecture day provided clinically active nurses and physicians from several countries with the latest findings on how to best manage pain in neonatal settings. The network which now consist of 18 researchers from different professions and academic levels presents itself on a five-language website: www.pearl.direct. The PIPP-R project has progressed according to the plan. The PIPP-R is translated into Finnish, Icelandic, Norwegian and Swedish. The cultural adaptation and validation should be finished in fall 2016. The members work on and plan for further collaborate projects. The next two steps are to translate and distribute educational material for parents via Internet and social media, and to establish a research and mas-ters course about pain in early life. The work has been secured by funding from Örebro University and Örebro University Hospital Research Foundation. Conclusions PEARL fulfils the need for a collaborative network for pain in early life researchers in the Nordic countries.

Aims Biomarker research seems to be somewhat controversial in pain medicine. Because pain is a subjective experience, renowned pain researcher Eija Kalso wrote in a 2004 Pain editorial that biomarkers for pain is an impossibility. However, in the same editorial, she also seemed to imply that what she called “biomarkers of (neuronal) activity in the nociceptive pathway” would be possible. Recently, I proposed the neologism “noci-marker” as a better term than “pain biomarker” for denoting attempts to find objective, measurable correlates to the neurobiological processes involved in different pain conditions. The purpose of the present conceptual work is to propose criteria for sensible hypothesis-generating research in the field of “noci-marker” research. Method Conceptual theoretical work, with examples from the literature. Results Criteria for sensible biomarker research in pathological pain conditions, together with examples from the literature, will be presented for discussion, including consideration of (work in progress): “Mirroring” rationale – which body fluid is studied? The example of saliva vs. cerebrospinal fluid. Time frame rationale – when is it sensible to look for what? The example of Cystatin C. Statistical considerations – univariate multiple testing vs. correlation structure of a whole data set. The example of multivariate data analysis by projection using SIMCA. The definition of patient cohorts – clinically and phenotypically. Relating findings to the literature and to systems biology. The example of Pain Networks. Reporting issues – how should the hypothesis-generating (explorative) nature of such studies be acknowledged? Conclusions Although it seems ethically dangerous and philosophically dubious to talk about “pain biomarkers”, searching for biological correlates to pathological activity in the nociceptive pathways (“noci-markers”) seems justified and conceptually possible.

Aims Children who experience pain and anxiety while undergoing interventions or treatments during hospitalization at a young age can experience negative feelings which can influence how they experience health care in the future. The purpose of the study was to evaluate the protocol of using a tablet computer as a source of distraction from pain and fear when children undergo needle insertion in a port catheter (port-a-cath®). Methods The study uses a quasi-experimental pretest-post test design with a sample of 14 children, 20 months to 16 years of age, 9 boys and 5 girls. Pain and fear were first evaluated without the distraction of a tablet computer. The second time pain and fear were evaluated while a tablet computer was used for distraction. The children evaluated their pain and fear with a 10 cm Numeric Rating Scale (NRS/VAS) and six faces scales in all cases except three. In those three cases the mothers evaluated the children’s pain and fear with the NRS, the Faces scale, or the Legs, Activity, Cry, Consolability scale (FLACC). Results The Shapiro-Wilk test showed a significant distribu-tion (p < 0.05) of pain and fear but most subjects did not feel any fear before the intervention. The mean score of pain was 2.90 (sd = 3.67) and the mean score for fear was 3.67 (sd = 3.76). No significant difference was found between pain and the fear prior to the intervention (p = 0.09). Children who felt fear prior to the intervention (n = 5) experienced significantly lower pain when a tablet computer was used (p<0.05). No difference was found between pain and fear by age or gender. No difference in pain was found by the type of distraction (p = 0.20). All subjects where highly experienced with needle insertions and some of them had developed their own approach to deal with the intervention. Conclusions More extensive research is needed in this area.

Aims Parenteral oxycodone is increasingly used worldwide to manage perioperative pain. Oxycodone doses required for adequate analgesia vary significantly between individuals. Our study investigated whether an analgesic plasma concentration could be determined for oxycodone and which factors affect it. Methods 1000 women undergoing breast cancer surgery were recruited to the study. Demographic data were collected and their cold and heat pain sensitivity and anxiety scores were measured preoperatively. After surgery, rest and motion pain intensities were measured. Intravenous oxycodone was administered until the patients reported satisfactory pain relief (NRS <4/10). At this point, plasma concentrations of oxycodone and its metabolites were determined. A second plasma sample for oxycodone deter-mination was taken when the patient requested a new dose of oxycodone. Genomic DNA was extracted from whole blood samples and the patients were genotyped for CYP2D6, CYP3A4 and CYP3A5 variants. Results The two oxycodone concentrations showed a strong correlation (r =0.84). The pain intensity measured during motion before oxycodone dosing correlated significantly with the plasma oxycodone concentration (geometric mean 35.3 ng/ml and CV % 66.4) required to achieve satisfactory analgesia (r = 0.38, p = 1.5 x 10 -33 ). The most important factors associating with postoperative pain intensity were type of surgery (breast conserving or mastectomy with or without axillary clearance) and the age of the patient. Older patients reported lower pain scores and required smaller oxycodone concentrations for satisfactory analgesia. CYP2D6, CYP3A5 or CYP3A4 genotypes did not significantly affect the oxycodone concentrations, but CYP2D6 genotype significantly affected the formation of the metabolites oxymorphone and noroxymorphone. CYP3A4 and CYP3A5 genotypes did not affect the metabolite formation. Conclusions Our results indicate that the more pain the patient experiences postoperatively the greater her minimum plasma oxycodone concentration must be to achieve satisfactory analgesia. Type of surgery and age significantly affect postoperative pain intensity.

Aims Studies have shown conflicting results regarding associations between physical activity (PA) and musculoskeletal pain among adolescents, and few have evaluated the impact of sport participation. Therefore, the aims of this study were to examine the associations between sport participation and persistent weekly pain by body region in a population-based sample of adolescents. Methods In this cross-sectional study, data from the adolescent part of the Nord-Trøndelag Health Study (Young-HUNT3) were used. Participants were asked how often during the last 3 months they had experienced pain in the neck-and-shoulders (NSP), low back (LBP) or lower extremities (LEP). The impact of sport participation and PA level on pain was evaluated using logistic regression analyses, stratified by gender, and adjusted for age, socioeconomic status and psychological distress. Results In total, 3765 boys and 3831 girls were included, mean age 15.8 years (SD 1.7). NSP was most prevalent (17%). Adolescents who participated in endurance sports had lower odds of NSP and LBP compared to non-participants. Participation in technical sports was associated with increased odds of LBP, and participation in team sports with increased odds of LEP, vs. no participation in the respective sports. Participation in strength sports and risk sports, vs. no participation, was related to higher levels of pain in all regions. Compared to a low PA level, a moderate PA level reduced the odds of NSP and LBP, whereas a high PA level increased the odds of LEP. Conclusion This study identified sports potentially protective, as well as sports associated with higher odds of NSP, LBP and LEP in a large population-based sample, and has increased the understanding of participation in sports as potential determinants of musculoskeletal pain among adolescents. Our findings highlight that types of sport adolescents participate in should be considered by healthcare professionals when evaluating their musculoskeletal pain.

Aims To explore how women perceive and are affected by treatment for painful endometriosis. Method Qualitative methodology with emergent design was used. Sixteen semi-structured interviews (including 3 follow-ups) with 13 women (age 20–47) treated at a pain clinic, were analysed with Grounded Theory. Results A preliminary model describes how women experience treatment for painful endometriosis and its consequences in one core category and three categories. The core category; Surviving painful endometriosis, described the women’s promoting strategies like Knowledge, Adaption and Planning, and inhibiting reactions as Anxiety and Resignation. The three interacting categories; Woman with painful endometriosis, included experiences of “The self” and “The body”. “The environment/significant others” described the environments’ support. Missed opportunities were described as a lack of participation in important life areas; “Social life”, “Career” and “Descendants”. “New possibilities” were experienced when pain disappeared or could be controlled. Dependent on health care included the experiences of “Treatments” from helpful to harmful and “Encounters with health care” from empowering to humiliating. Conclusions The suffering of women when exposed to painful endometriosis can lead to missed opportunities in several important areas of life. Hormonal and symptomatic treatments, as well as positive encounters of health care are important for the women’s possibility to develop working surviving strategies.

Aims (1) To determine the distribution and determinants of opioid use among chronic nonmalignant pain (CNP) patients. (2) To identify the patient, treatment and socioeconomic characteristics as determinants for potential risk groups. We hypothesized that CNP patient who use opioids for more than 1 year would differ in demographics and comorbidity from other patients who use opioids for less than 6 months. Methods National registers were used to include patients beginning opioid therapy in the period 01/01/2000-31/12/2014 (incl.). The cohort consists of adults aged 16 years or older who redeemed at least one prescription for an opioid product and residing in Denmark, analysing only patients who survived for at least two years. Follow-up minimum one year after the last redeemed opioid prescription or to 31/12/2015. Participants are included at first redeemed prescription for an opioid product using the ATC codes N02AA01-N02AX06. Patients were then classified as either opioid use for more than 1 year (group A), as opioid use for more than 6 months but less than 1 year (group B) and opioid use equal to or less than 6 months (group C). Results The quantity of sold opioids has been increasing during 1997-2008, with a fairly stable but high level since. It is expected that we will be able to determine patterns and the distribution of opioid use among CNP patients in Denmark. Consequently, describing potential risk groups of opioid use based on patient, treatment, comorbidity, socioeconomic and demographic characteristics. Data analysis is ongoing. Conclusions It is expected that this study will serve as a significant supplement of existing knowledge in the area of opioid consumption among CNP patients in Denmark. In a future perspective of prevention and health promotion initiatives of the growing public health problem CNP, it might be beneficial to include perspectives of risk assessment of long-term opioid use. http://medstat.dk/ statistics for annual sales of medicines in Denmark 1996–2014.

Aims Systemic low-grade inflammation can be initiated in vivo after traumatic injury or in chronic diseases as neurodegenerative, metabolic and autoimmune diseases. Coupled cell networks are target cells leading to the spread of inflammation and changes in biochemical cellular parameters. Do astrocytes and chondrocytes behave in a similar way in an inflammatory reactive state with respect to Ca 2+ signaling, actin filaments rearrangement, receptor properties, pro-inflammatory cytokine release etc? Methods Primary cultures of astrocytes and chondrocytes, respectively, were incubated with lipopolysaccharide (LPS) (10 ng/ml, 24h) or interleukin-1β (IL-1β) (5ng/ml, 24 h) to induce inflammatory reactivity. Ca 2+ signaling, Na + /K + -ATPase-, connexin 43 (Cx43)-, and Toll-like receptor 4 (TLR4)- expressions, actin filament organization, and IL-1β release were analyzed. Results Stimulation with IL-1β or LPS altered the Ca 2+ signaling from single peaks to oscillating waves and increased the expression of Cx43 and TLR4, and decreased expression of Na + /K + -ATPase. A disruption of the actin filaments with more pronounced ring-formed structures was found in inflammatory induced astrocytes and chondrocytes which in turn affects Ca 2+ oscillations. Additionally a release of active matrix metallopeptidase-13 was found in media from IL-1β stimulated chondrocytes. Conclusions Our data show that cellular mechanisms of healthy chondrocytes as well as inflamed, resemble the coupled cell networks of astrocytes. Chronic, low-grade inflammation can influence coupled cell networks in one or several organs, leading to co-morbidity. It is crucial that inflammatory affected cells in various organs are restored back to a physiological non-inflammatory homeostasis in order to prevent tissue degradation and pain.

Aims A country’s use of opioids is frequently debated in the public, usually based on rough figures from prescription databases made for consumption registration purposes. However, these databases hold much more detailed information that can be processed to increase knowledge and insight into nationally opioid prescribing-behaviour. This study aims to provide a more detailed picture of opioid prescribing and its changes in Denmark, Sweden and Norway during 2006-2014. Methods Data on opioid-use (ATC; N02A) were downloaded from each country’s publically assessable prescription-databases. Consumption-data were converted from defined daily doses (DDDs) to mg oral morphine equivalents (omeqs). Changes in choice of opioid-types, use and number of users were presented using descriptive statistics and compared. Results Opioid users : During the whole period, Norway had the highest, and Denmark the lowest, number of opioid users/1000 inhabitants. In 2006, Norway, Sweden and Denmark had 98, 79, 66 users/1000 inhabitants. In 2014 the numbers were 105, 78, 75 users/1000 inhabitants, respectively. Opioid use/user : During the whole period, Norway had the lowest, and Denmark the highest use/user. In 2006, the mean use/user was 1979, 3615, 6025 mg omeq/user in Norway, Sweden and Denmark respectively. In 2014 the corresponding use was 2426,3473,6361 mg omeq/user. The preferred choices of opioid-types changed during the period for all three countries. The balance between use of weak or strong opioids showed more prominent changes for Norway and Sweden compared to Denmark. Conclusions Three nations, closely related in culture and geo graphically, showed significant differences and changes in opioid prescribing behaviour. This knowledge can easily be overlooked using the traditional way of presenting opioid consumption statistics. More detailed and clinically relevant presentation can increase the knowledge of doctors’ opioid prescribing behaviour, that can be related to changes in the society or health care system, like demography, legislation and guidelines from authorities.

Aims To relate changes in the number of opioid users in Denmark, Norway and Sweden during 2006-2014 to changes in national regulatory and economic incentive factors. Methods The material consists of data drawn from the national prescription databases in Denmark, Norway and Sweden. Data on the number of opioid users per 1000 inhabitants were collected for all ages, both sexes and for the period 2006-2014. Concomitant changes in regulatory or economic incentives were identified and related to the drug statistics. Results For all opioids in the period 2006-2014 Denmark had the lowest number ofusers but the largest increase in users. Norway had the highest number of users but a lower increase. The number of users in Sweden was very stable showing no change in number of users. The number of morphine users in Denmark increased from 2009 to 2014. The number of users of oxycodone decreased from 2010 to 2014. The Danish health authorities recommended using morphine as first drug of choice in 2010 and warned about potential drug dependency of oxycodone in 2011. In Sweden the number of users of oxycodone increased over the period with the largest increase from 2012 to 2013. The number af tramadol users decreased from 2011. Prior to these changes tramadol was declared to be classified as an addictive drug 2011. Conclusions Changes in the countries’ opioid use appeared in the public prescription-databases in a timely manner after introduction of national recommendations not to use oxycodone and prefer morphine as first choice, or classify tramadol as an addictive drug. National drug statistics show the end-result of the doctors’ prescribing behavior and the population’s use of opioids. Thorough investigation of prescription-data can help to detect and explain the interplay between culture, society and medical reasons for prescribing opioids.

Aims We aim to characterize the effects of variation within ADRB2 -gene on pain and opioid requirements in human patients. We will assess ADRB2-OPRM1-6TM heterodimer as a molecular mechanism, potentially explaining pronociceptive and antianalgetic effects, using preclinical in vitro and in vivo models. We will further assess clinical significance via its genetic proxy, rs563649 in humans Methods In humans, experimental and postoperative pain and opioid responses were assessed in 1000 breast cancer surgery patients. Association of ADRB2 (n = 40) and OPRM1 (n = 1) polymorphisms was assessed using linear regression and analysis of variances (ANOVA). In vitro methods involved immunofluorescence microscopy (IF), cellular localization and translocation of 6TM/β2AR-heterodimers and Ca 2+ -measurements. Behavioral in vivo characterization was performed in mice using formalin, von Frey, hot plate and cold plate tests after administration of morphine, specific OPRM1-6TM agonist IBNtxA and ADRB2-antagonist ICI118,551. Results In humans, several ADRB2 SNPs were associated with pain and opioid phenotypes. The strongest associations were seen between cold pain phenotypes and rs17108817 & rs11957757 (p < 0.0001). In vitro , coexpression with β 2 -Ars increased translocation of 6TM-MOR to plasma membrane and Ca 2+ responses after treatment with selective 6TM-agonist, IBNtxA, compared with the cells expressing OPRM1-6TM alone. In vivo , co-administration of P2AR selective antagonist ICI 118,551 increased analgesic efficacy of opioids in a synergistic manner and reduced opioid-induced hyperalgesia. Conclusions Our findings suggest that ADRB2 and genetic variation in ADRB2 -gene are involved in the modulation of human pain and opioid responses. 6TM-MOR/P2-AR heterodimerization represents a molecular mechanism causing excitatory cellular effects and sufficient explanatory potential to explain pronociceptive and antianalgesic effects. Our animal findings further confirmed the concept of β 2 -AR and 6TM-MOR interaction in vivo . We suggest that co-administration of β-blockers with opioids might increase efficacy and safety of OPRM1 agonists.

Aims The aim of the study was to describe the clinical features and clinical pathway of pediatric CRPS patients in HUH Children’s Hospital. Methods This retrospective study included patients admitted to the pediatric pain clinic for CRPS during six years 2008-2013. Data on time from the first symptoms to diagnosis, first appointment at the pain clinic, and symptom resolution, as well as demographic and clinical symptoms were extracted from patient records. Results Forty patients were clinically diagnosed with CRPS during the time period without using the Budapest Criteria. 75% of the patients were female, median age was 12, and in 90% of the cases the CRPS was localized in the lower extremity. The median time from first symptoms to the CRPS diagnosis was 8.5 weeks (range 0-47), to first appointment with the pain physician 10 weeks (range 2-47), and to symptom resolution 35 weeks (range 10-131). Eleven out of forty patients (27.5%) were not symptom-free at the end of the treatment period. Most common clinical finding was allodynia or hyperalgesia of the afflicted area (70%). Conclusions Compared to an earlier study performed in our hospital (retrospective study of seven years, n = 18), the number of patients has more than doubled, maybe due to better awareness of the syndrome. Our findings about demographics and localization of CRPS are in agreement with previous literature. Time to reaching diagnosis, the small number of consultations and radiographs show that CRPS is well known among pediatric orthopedic surgeons. Many Budapest criteria that are now considered important diagnostic findings were not highly prevalent in our patients (e.g. prior trauma, color changes of skin), although patient records were not always clear about the findings leading to diagnosis. The Budapest criteria should be used to standardize the diagnosis also in our pediatric patients.

Aims Low back pain and sciatica after disc herniation may be caused by mechanical compression of the nerve roots, but also by the release of pro-inflammatory agents including growth factors from the nucleus pulposus (NP). Methods Here, in an animal model mimicking the clinical situation following disc herniation, CLIA protein analyses, extracellular single-cell recordings in the spinal dorsal horn and qPCR were performed to examine the nociceptive signaling due to disc herniation. Results The present data demonstrated that EREG may be released from NP - and that administration of EREG onto the spinal dorsal nerve roots increased spontaneous activity in nociceptive neurons. An up-regulation of EGFR and HER4 in the dorsal horn as well as an up-regulation of HER3 in the DRG were demonstrated after application of NP onto the dorsal nerve roots. Conclusion Our findings suggest that EREG and signaling through its receptors may be involved in pain hypersensitivity and other sensory abnormalities after disc herniation.

Aims To describe patients with persistent pain participating in multimodal rehabilitation with language interpreter (MMRI) with regard to demographic data, pain, anxiety, depression, fear of movement, health related quality of life before and after rehabilitation. Methods The university rehabilitation departments in Lund and Stockholm developed multimodal rehabilitation programmes for patients who cannot participate in ordinary programmes due to insufficient knowledge in Swedish. From 2014 to 2015, 50 patients participated in the MMRI. Data was collected at admission and discharge with instruments from the Swedish quality registry for pain rehabilitation. The assessments included health related quality of life (EQ5D), anxiety and depression (HADS), fear of movements (TSK), disability (PDI). Preliminary results Fifty patients participated in MMRI. Seventy-eight percent were women, and 88% were born outside Europe. Compared to patients participating in Swedish regular rehabilitation programmes (MMR), the level of education was low, 44% had finished high school (55% in MMR in Sweden) and 8% university (27% in MMR in Sweden). Also the distribution of pain differed; in MMRI 40% reported pain with varying localization compared to 33% in MMR. Both groups were frequent health care seekers, even though MMRl’s patients reported a higher frequency of visits than MMR regular patients; 94% of MMRl’s patients compared to 70% MMR patients were seeking physicians more than 4 times due to pain during the previous year. Both groups report very low health related quality of life. In the MMRI group, at admission, the EQ5Dindex was 0.088 (md) (MMR 0.157). This can be compared with 0.83, the value for the Swedish norm population. Conclusions Patients participating in MMRI, compared to patients participating in MMR, reported poorer health, higher rate of visit to physicians due to pain and less higher education than other, Swedish speaking pain patients attending to the country pain programmes.

Aims The purpose of this cross-sectional study was to inves-tigate the occurrence of symptoms related to dysfunctional breathing (DB) in chronic pain patients and to examine factors associated with these symptoms. Methods A questionnaire was sent to 527 adults referred to out-patient pain clinics at Oslo university hospital. The questionnaire provided demographic data, Brief Pain Inventory, Spielberger state- trait anxiety inventory, and Nijmegen questionnaire (NQ). Multiple regression analyses were performed using SPSS. Results A total of 108 patients (20%) responded to the questionnaire and was included. Mean age was 49 years and two third of the participants were female. More than four out of ten had a NQ score ≥ 23 (a conservative cutoff value for DB). The median NQ score in the sample was 19. Trait-anxiety (Beta = .412, p < 0.001) and maximal pain intensity during the past week (Beta = .264, p = 0.004) predicted symptoms related to DB even when controlling for age and gender. Conclusions The study shows that a large portion of patients with chronic pain experiences symptoms that have been associated with hyperventilation and DB and at a higher level than previously reported. Although trait-anxiety is a strong predictor for symptoms related to DB, we find it interesting that maximal pain intensity during the last week also was associated with these symptoms. The cross-sectional design, low response rate, and lack of diagnoses limit our ability to draw conclusions about causal relationship and extrapolate to a larger populations of patients with chronic pain.

Background Pneumococcal vaccination for children was introduced in Sweden in 2009. For more than two decades, previous studies have shown that anesthetic cream Emla® has good effect in reducing vaccine-related pain. Even today health care workers claim “children forget quickly, and it (the pain) goes away”, this ignorance causes pain in children not treated or treated in one for the child and his guardians satisfactorily way. Purpose The purpose of this intervention study was to compare the effect of Emla ® cream for pain relief or no pain relief in connection with the first pneumococcal vaccination at three months of age in child healthcare. Method The study included 72 children who, at three months of age received their first pneumococcal vaccine (Prevenar 13®). The children were randomized, 36 children received pneumococcal vaccination with placebo cream and the other 36 children received the intervention, Emla®-cream. Result The result shows that anesthetic cream Emla® significantly reduces pain when FLACC is used as a pain assessment tool and the children begin to cry significantly later than children who received placebo cream. An interesting secondary finding of the study was that the younger the child was the stronger was the reaction to pain. Conclusion The infant needs to be treated as an autonomous individual with full integrity. We recommend Emla® to be used and applied in vaccination when the children are three-, five- and twelve months.

Aims To investigate the use of Complimentary/Alternative therapy for chronic pain in nationwide sample. Methods In this cross-sectional study a postal questionnaire measuring socio-demographic variables (e.g. gender, education, income and residence), pain characteristics (severity and interference with daily life), health related quality of life and use of Complimentary/Alternative therapy for chronic pain, was sent to a sample of 4500 individuals randomly drawn from the national population of Iceland. The relationships between sociodemographic and pain related variables and pain related use Complimentary/Alternative therapy among participants reporting chronic pain (≥3 months) were tested. Results The prevalence of chronic pain (≥3 months) among respondents was 47.5%. Among participants reporting chronic pain, 45.5% ( n = 343) reported having consulted some kind of Complimentary or Alternative therapy for their pain the previous six months and this was more prevalent among women than men. Most usual kind of therapists consulted was Acupuncturists (21.4%) and Chiropractors (18.3%). There were some gender differences in what kind of therapy people had consulted. Women were more likely than men to have consulted Acupuncturist while men consulted a Chiropractor more often than women. Logistic regression analysis showed that predictors for use of Complimentary/Alternative therapy for chronic pain were gender, urban residence and pain severity. The use of Complimentary/Alternative therapy was not related to education, family income or health related quality of life. Conclusions Women and urban residents are more likely than men and rural residents to seek Complimentary/Alternative therapy for chronic. People are more likely to seek Complimentary/Alternative care for chronic pain the more severe pain is.

Aim The current study aimed to explore the effect of conditioned pain modulation (CPM) on the long-term potentiation (LTP)-like pain amplification induced by peripheral 10 Hz conditioning electrical stimulation (CES). Methods Sensory changes and neurogenic inflammatory vas-cular reactions induced by 10 Hz CES were assessed in twenty subjects in a randomized crossover design involving two experimental days separated by at least one week. The CPM effect was activated by cold pressor test (CPT) (4 °C) which was applied immediately before the 10 Hz CES in the active session and 32 °C water was used in the control session. Perceptual intensity ratings to single electrical stimulation (SES) at the conditioned skin site and to mechanical stimuli (pinprick and light stroking) in the immediate vicinity of the electrode for CES were recorded. Superficial blood flow (SBF), skin temperature (ST), and heat pain threshold (HPT) were also measured. The pain intensities during the CES process were recorded and the short-form McGill Pain Questionnaire (SF-MPQ) was used for assessing the pain experience. Results CPT reduced the pain perception increments to pin-prick (12.8 g) and light stroking stimuli after 10 Hz CES compared to the control session. Moreover, CPT resulted in lower pain intensity ratings during the CES process but without significant changes in the SF-MPQ scores between the two sessions. The SBF and ST were found to increase after CES and then gradually decline but without differences between the CPT and the control sessions. No CPM effect was found for HPT and pain intensity increments to SES. Conclusions The cold pressor test inhibited heterotopic perception amplification to mechanical stimuli after conditioning electrical stimulation. The results indicate that endogenous descending inhibitory systems may affect pain-amplificatory mechanisms.

Aims In a previous comparative two-dimensional gel electrophoresis study [1], we described seven cerebrospinal fluid (CSF) proteins highly discriminating between neuropathic pain patients and healthy controls. The aims of the present follow-up work were to examine the multivariate inter-correlations between all identified isoforms of these seven proteins. The focus was not on discriminant analysis but rather on the internal correlation structure between these proteins in healthy controls vs neuropathic pain patients. Our hypothesis was that neuropathic pain is associated with a disrupted correlation structure between these protein isoforms. Moreover, focusing on the patients, we wanted to regress clinical pain parameters (pain intensity and pain duration), using all the proteomic data (260 proteins) of our previous study [1] as predictor variables, thereby testing the hypothesis that the abovementioned seven discriminating proteins and/or their isoforms would be among the proteins having the highest predictive power for clinical parameters. Methods Biochemical identification of isoforms of the above mentioned seven proteins. Principal component analysis (PCA) was used to describe and compare the correlation structures of patients vs. healthy controls, and orthogonal partial least square (OPLS) analysis was used to regress clinical parameters [2,3]. Results We identified 5 isoforms of angiotensinogen, 18 isoforms or fragments of alpha-1-antitrypsin, 5 isoforms of haptoglobin, and 5 isoforms of pigment epithelium derived factor. In patients and using PCA, a down-regulated fragment of alpha-1-antitrypsin correlated to another up-regulated fragment of alpha-1-antitrypsin, indicating a possible physiological relationship. The OPLS regression of clinical parameters in patients also seems to yield interesting results (work in progress). Conclusions Some of the seven proteins that were the main results of our previous study [1] reappear in different ways in the results of the present study. This strengthens our interest in characterizing the nature of their post-translational modifications.

Aims Neck pain is frequent and many develop on-going neck pain after the initial onset. Studies on clinical neck pain suggested that altered axioscapular muscle activity may be an important factor in on-going neck pain. This study investigates the effect of bilateral experimental neck pain on axioscapular muscle activity during standardised resisted arm movements. Methods 25 healthy participants were recruited for this single blinded cross-over study. Experimental pain was induced by bilateral injection of hypertonic saline into the splenius capitis muscle. Isotonic saline was used as a control. Pain intensity was recorded using an electronic visual analogue scale (VAS; 0-10 cm). Participants performed standardised arm movements, from a seated position, while wearing 1 kg wrist weights. Six arm abduction movements (30° to frontal plane, 3 per side) were performed to an angle of 140°. Each movement consisted of two 3 s phases (up/down) and was separated by a 6 s break, before moving the opposite arm. Surface electromyography (EMG) was recoded from 8 bilateral muscles. Recordings were done before, immediately after, and 5 min after the experimental pain. Root-mean-square (RMS) of the EMG signals were extracted for each muscle and averaged for the 3 trials. Data was compared between sides and no differences were identified after which data was pooled for further analysis. Results During the painful condition for the slow upward movement, a reduced RMS-EMG activity was found for the ipsilateral upper trapezius (P< 0.01). In addition, increased RMS-EMG was found bilaterally for the erector spinae muscle (P< 0.01). Conclusion Bilateral experimental neck reorganise axioscapular and trunk muscle activity during resisted, slow upward movement. The results of this supports previous studies on neck pain patients suggesting neck pain is linked to axioscapular function and underpins the necessity to include the shoulder girdle in assessment and rehabilitation of neck pain patients.

Aims Mast cell proteases comprise up to 25% of the total protein content within mast cells and have various functions that are still poorly understood but can be either protective or pro-inflammatory.Three ofthose proteases in mice have been identified as the closest functional homologues to human mast cell proteases, and in this currently ongoing study we are investigating if they play a role in itch and tissue injury pain, and if they do, what the possible mechanism behind that could be. Methods Knock-out mice were generated, lacking either one or multiple proteases. To evaluate itch, the animals ( n = 8–10) were injected intradermally with histaminergic (histamine, compound 48/80) and non-histaminergic (protease activated receptor 2 (PAR2) agonist, chloroquine) pruritic substances and their itch behavior over 1 h scored. Formalin injection ( n = 20) in the hind paw was used as a model for tissue injury pain, where the mice were monitored for pain behavior for 1 h following the injection. Age and gender matched C57BL/6 mice were used as controls. Results Mice lacking three of the proteases had twice as many scratching episodes in response to histamine ( P =0.016) and compound 48/80 ( P =0.034) than controls. The non-histaminergic substances chloroqine and PAR2 are more potent pruritogens but difference was not seen in itch levels between genotypes. Furthermore, the protease-deficient mice exhibited a more pronounced pain response during the inflammatory stage (10–60 min after formalin injection, P = 0.025) of the tissue injury test. Conclusions The mouse mast cell proteases have a protective role against histaminergic itch and in acute inflammation following a tissue injury. The exact mechanism remains unclear at present as the proteases cleave a variety of different pro-inflammatory substrates and can act in complimentary fashion by cleaving the same substrates but at different sites.

Aims To employ a human experimental model of opioid-induced bowel dysfunction (OIBD) in healthy volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility, assessed by questionnaires and regional GI transit times. Methods Twenty-five healthy males were randomly assigned to oxycodone or placebo for five days in a double-blind, crossover design. Adverse GI effects were measured with bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptoms questionnaire, and bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system and segmental colonic transit times were determined using a custom Matlab® graphical user interface. Results GI symptom scores increased significantly across all applied questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 h ( P < 0.01), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 h ( P <0.05), rectosigmoid transit time from 2.7 to 9.0 h ( P <0.05), and colorectal transit time from 18.6 to 38.6 h ( P <0.01). No association between questionnaire scores and segmental transit times were detected. Conclusions Self-assessed adverse GI effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of OIBD.

Background and aims P2X7 is a purinoceptor and non-selective cation channel that is activated by extracellular ATP, especially in immune and glia cells. Activation of P2X7 triggers the secretion of several pro-inflammatory substances, such as IL- 1P, IL-18, TNF-α, and nitric oxide. P2X7 activation contributes to the pro-inflammatory response to injury or bacterial invasion and mediates apoptosis. It has been implicated in physiological and pathological conditions such as bone tissue remodelling, inflammation, oncogenesis, depression, and inflammatory, neuropathic and chronic pain. Here, we aim to characterize the effects of variation within the P2RX7 gene, which encodes the P2X7 receptor, on pain and opioid requirements in human patients. Methods Pain was assessed in Norwegian and Finnish cohorts. The Norwegian cohort represents the 6th wave of the Tromsø Study, a longitudinal and cross-sectional population based study ( N = 3700), whereas the Finnish cohort (BrePainGen) consists of patients who underwent breast cancer surgery ( N = 1000). For both cohorts, experimental pain data were analyzed. Pain intensity and tolerance were assessed with cold pressor test and after standardized noxious heat stimulation in both cohorts. In addition, data on acute postoperative pain and opioid requirements were analyzed in the BrePainGen cohort. Postoperative pain and opioid responses were followed during 20 h after surgery. In total, 29 single nucleotide polymorphisms (SNPs) in P2RX7 were genotyped and their association with outcome variables was assessed using linear regression and analysis of variances (ANOVA). Results Several P2RX7 SNPs were associated with the pain phenotypes. The strongest associations were seen with cold pain intensity and tolerance. The results of this study will be presented at the meeting. Conclusions Our results suggest that P2X7 and genetic varia-tion in the P2RX7 -gene are involved in the modulation of human pain responses.

Aims Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting side effect in the use of the platinum-based antineoplastic drug oxaliplatin as a treatment for colorectal cancer. Currently there is no treatment available to reverse the neurotoxicity which presents as pain, sensory loss and cold allodynia in up to 80% of patients. The aim of this study is to investigate if pregabalin can reverse the allodynia caused by oxaliplatin in CIPN. Methods CIPN was induced in 10 male C57BL/6 mice (6 weeks-old) with a single intraperitoneal injection of oxaliplatin (15 mg/kg i.p.). Signs of thermal and mechanical allodynia were assessed from baseline to 20 days after injection by Cold/Hot plate (Bioseb, France) at 20 °C and hand-held von Frey (vF) hairs of gradually increasing weights. Pregabalin (3 mg/kg and 10 mg/kg p.o.) was administered to treat CIPN. Results Mechanical and thermal allodynia were established 3 days post-oxaliplatin injection and remained stable for 14 days. At day 15, pregabalin (3 mg/kg p.o.) reversed mechanical allodynia to baseline scores at 2 h (H) post-dosing and thermal allodynia at 1 and 2H post-dosing. Following a 2-day wash out where scores returned to neuropathic baseline, pregabalin (10 mg/kg p.o.) reverted scores for mechanical and thermal allodynia to baseline scores at both 1 and 2H. Thermal testing was performed either immediately after vF or alone and our results were similar, showing no iatrogenic effects of vF on thermal sensitivity. Correlation analysis of the responses to thermal and mechanical stimuli showed no significant trend, indicating that oxaliplatin-induced peripheral neuropathy affects the mechanical and thermal modalities in different ways. Conclusion Oxaliplatin-induced peripheral neuropathy as measured by thermal and mechanical allodynia is reversible by a single dose of pregabalin. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 642720. RM is funded by a Marie Sklodowska-Curie grant agreement No. 642720 doing a joint PhD with the Royal Veterinary Collage and Transpharmation Ltd. AF and NU are employees of Transpharmation Ltd.

Background and purpose Depression is a frequent co-morbid diagnosis in chronic pain, and has been shown to predict poor outcome. Several reviews have described the difficulty in accurate and appropriate measurement of depression in pain patients, and have proposed a distinction between pain-related distress and clinical depression. Aims of the current study were to compare (a) the overlap and differential categorisation of pain patients as depressed, and (b) the relationship to disability between the Structured Interview for DSM-IV (SCID-Depression module) and the Hospital Anxiety and Depression Scale (HADS-D). Methods Seventy-eight chronic back pain patients were administered the SCID-D, the HADS-D and the Pain Disability Index (PDI). Results Significantly more patients were categorised with possible and probable depression by the HADS than the SCID-D. Results from Receiver Operating Characteristic (ROC) curve analysis suggested that the HADS-D provided better discriminatory ability to detect disability, demonstrating a better balance between sensitivity and specificity compared to the SCID-D, although a direct comparison between the two measurements showed no difference. Conclusions The HADS-D is a reasonably accurate indicator of pain-related distress in chronic pain patients, and captures the link between disability and mood. Implications It is likely that the SCID-D is better suited to identifying sub-groups with more pronounced psychiatric disturbance. Perspective Several reviews have proposed a distinction between pain-related distress and clinical depression. This study compared the overlap and differential categorisation of pain patients as depressed and the relationship to disability between the Structured Interview for DSM-IV (SCID-D; Depression module) and the Hospital Anxiety and Depression Scale (HADS-D). © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.