Volume 3, Issue 3

Background The definition of neuropathic pain has recently been changed by the International Association for the Study of Pain. This means that conditions such as fibromyalgia cannot, as sometimes discussed, be included in the neuropathic pain conditions. However, fibromyalgia and peripheral neuropathic pain share common clinical features such as spontaneous pain and hypersensitivity to external stimuli. Therefore, it is of interest to directly compare the conditions. Material and methods In this study we directly compared the pain modulation in neuropathic pain versus fibromyalgia by recording responses to a cold pressor test in 30 patients with peripheral neuropathic pain, 28 patients with fibromyalgia, and 26 pain-free age-and gender-matched healthy controls. Patients were asked to rate their spontaneous pain on a visual analog scale (VAS (0–100 mm) immediately before and immediately after the cold pressor test. Furthermore the duration (s) of extremity immersion in cold water was used as a measure of the pain tolerance threshold, and the perceived pain intensity at pain tolerance on the VAS was recorded on the extremity in the water after the cold pressor test. In addition, thermal (thermo tester) and mechanical stimuli (pressure algometer) were used to determine sensory detection, pain detection, and pain tolerance thresholds in different body parts. All sensory tests were done by the same examiner, in the same room, and with each subject in a supine position. The sequence of examinations was the following: (1) reaction time, (2) pressure thresholds, (3) thermal thresholds, and (4) cold pressor test. Reaction time was measured to ensure that psychomotoric inhibitions did not influence pain thresholds. Results Pain modulation induced by a cold pressor test reduced spontaneous pain by 40% on average in neuropathic pain patients, but increased spontaneous pain by 2.6% in fibromyalgia patients. This difference between fibromyalgia and neuropathic pain patients was significant ( P < 0.002). Fibromyalgia patients withdrew their extremity from the cold water significantly earlier than neuropathic pain patients and healthy controls; however, they had a higher perceived pain intensity on the VAS than neuropathic pain patients and control subjects. Furthermore, neuropathic pain patients had a localized hypersensitivity to mechanical and thermal stimuli in the affected area of the body. In contrast, fibromyalgia patients displayed a general hypersensitivity to mechanical and thermal stimuli when the stimuli were rated by the VAS, and hypersensitivity to some of the sensory stimuli. Conclusions These findings are the first to suggest that a conditioning stimulus evoked by a cold pressor test reduced spontaneous ongoing pain in patients with peripheral neuropathic pain, but not in fibromyalgia patients when directly compared. The current study supports the notion that fibromyalgia and neuropathic pain are distinct pain conditions with separate sensory patterns and dysfunctions in pain-modulating networks. Fibromyalgia should therefore not, as sometimes discussed, be included in NP conditions. Implications On the basis of the findings, it is of interest to speculate on the underlying mechanisms. The results are consistent with the idea that peripheral neuropathic pain is primarily driven from damaged nerve endings in the periphery, while chronic fibromyalgia pain may be a central disorder with increased activity in pain-facilitating systems.

Background and purpose Pulsed radiofrequency (PRF) is widely used for the treatment of chronic pain, although its mechanism of action is not known. The evidence of efficacy of PRF for neuropathic pain (NP) conditions is limited. A double-blind, randomized, sham-controlled parallel study was conducted to evaluate the efficacy and safety of PRF in the treatment of peripheral posttraumatic NP. Methods Forty-five patients with peripheral posttraumatic NP in their upper or lower limb were randomly assigned to receive PRF or sham treatment to the injured peripheral nerve (s) causing peripheral posttraumatic NP. Only patients whose pain intensity was at least 5 on numerical rating scale (NRS) 0–10 and who had suffered from their NP for at least 6 months were included. All patients had dynamic mechanical allodynia or pinprick hyperalgesia in their painful area. They had achieved temporary pain relief of at least 50% with a local nerve block performed at a previous visit. The primary efficacy variable was the difference in 3-day mean pain intensity score from the baseline to 3 months. Other variables included response defined as ≥30% reduction in mean pain intensity at 3 months compared to baseline, Neuropathic Pain Scale (NPS) results, health related quality of life (SF-36) and adverse effects. The skin was anesthetized with 1% lidocaine. A radiofrequency needle was introduced through the skin, and then guided to a SMK cannula (52, 100 or 144mm depending on the target nerve) with 4 or 5mm active tip (SMK-C5-4, SMK-C10-5, SMK-C15-5, Radionics®, Burlington, MA, USA). The nerve was located accurately by stimulating at 50 Hz (threshold <0.5 V). Sham treatment or PRF was applied for 120s 1–4 times at each treatment point (Radionics®, Burlington, MA, USA). The total treatment time was up to 8 min. Both patients and clinicians were blinded during the whole treatment and follow-up period. Results Forty-three patients were included in the analyses. There was no statistically significant difference between PRF and sham treatment for the primary outcome efficacy variable. Seven patients (3 in PRF group and 4 in sham treatment group) achieved ≥30% pain relief (difference between groups was not significant). There was no statistically significant difference in the NPS or any dimension of SF-36 between the treatments. Eighteen patients reported adverse effects. They were mild and did not necessitate any treatment. Transient pain was reported by 17 patients, local irritation by 5 patients and local inflammation by 1 patient. There was no significant difference between the groups in the presence of adverse effects. Conclusions PRF was well tolerated, but this study failed to show efficacy of PRF over sham treatment for peripheral posttraumatic NP. Implications Based on our results, we do not recommend PRF for peripheral posttraumatic NP. More research of the possible use of PRF for various pain conditions is needed to determine its role in the management of prolonged pains.

Background and aim The curious phenomenon phantom limbs early became the object of research, and its underlying mechanisms have been discussed over the years. The complex nature of phantom phenomena makes interpretation of the results ambiguous, regarding both prevalence and the accompanying suffering. There is a lack of knowledge about how amputees experience the meaning and consequences of phantom phenomena. The present aim, therefore, was to investigate how individuals, in an interview situation, described the qualities of possible perceived phantom phenomena, and how their experience affected their lives one month after the amputation/mastectomy. Methods Twenty-eight women and men who had undergone a limb amputation or mastectomy were interviewed. The focused, narrative-oriented interviews were transcribed verbatim and the scripts were analysed with content analysis. Results One month after the amputation the informants described and related their phantom pain and phantom sensations in sensory-discriminative, motivational-affective and cognitive-evaluative dimensions. The phantom sensations were experienced mainly as more agonizing than the phantom pain. Despite both the high intensity of and the high annoyance at the phantom pain and phantom sensations, a majority felt that the phantom phenomena were not a hindrance in their attempts to recapture ordinary life. But when the hindrance was evaluated as high, the annoyance was evaluated as the highest possible for both phenomena or for the phantom sensations alone, never for phantom pain alone. The interviewees’ reported attitudes of hindrance were also described and estimated in the light of their sociocultural circumstances. Thus, other preceding and/or co-existent pain conditions as well as factors such as pre-operative information, the respondents’ views on pain treatment, and their knowledge and understanding of phantom phenomena were mentioned and related to the pain-producing situation. Two-thirds of the interviewees had received post-surgical information and for some, the phenomena were well-known from earlier experience. A majority applied some version of the medical explanation model, irrespective of age or level of education. However neither information nor medical explanation, or both, sufficed for them to understand their own phantom phenomena. Thus, differences between the concepts explanation and understanding seemed significant for the annoyance related to the phantom phenomena. Regarding background data (i) the majority of the interviewees had had pre-amputation pain problems; (ii) the breast-cancer phantoms differed in several ways; (iii) there were some age and gender differences in the descriptions of hindrance. Conclusions and implications These findings highlight the importance of observing the individual approach to the phenomena as a process of evaluation and selection. In addition, experience and understanding of the phantoms also have sociocultural aspects. There follows the need for individualized communication and information from the clinician, and for incorporating a socioscientific and meaning-centred approach in future studies. The present insights could also be of value in other iatrogenic pain conditions.

Background and purpose In animal studies, enhanced sensitivity to painful stimuli succeeding chronic stress has been reported, while acute stress is reported to induce analgesia. Human studies on the effect of mental stress on pain are more equivocal. A disturbed stress-response resulting in an increased sensitivity to painful stimuli has also been discussed as a potential mechanism for e.g., the fibromyalgia syndrome. Endogenous analgesia may be studied in humans by measuring the analgesic effect of heterotopic noxious conditioning stimulation. In neurophysiological animal studies this phenomenon was originally denoted “diffuse noxious inhibitory controls” (DNIC), but for human studies it has been suggested to use the term conditioned pain modulation (CPM). The clinical relevance of aberrances in CPM is not clear. Inhibitory CPM is reported as being reduced in several medically unexplained syndromes with musculoskeletal pain aggravated by mental stress. However, whether the reported reduced CPM effects are causally related to clinical pain is unknown. In the present study the effect of a mental stressor on CPM is studied. Methods With tourniquet-induced pain as the conditioning stimulus we estimated the CPM effect in twenty healthy subjects. Heat pain threshold (HPT), supra-threshold heat pain level (SHPL) and pressure pain threshold (PPT) were used as test stimuli. Measurements were performed at baseline, after a stressful task and after a non-stressful task presented in a blinded cross-over design. We used repeated-measures ANOVAs in the analysis with simple contrasts for post hoc analysis. Results With a ANOVA repeated measures model we found a significant task effect ( F = 18.5, p ≤ 0.001), indicating that CPM was successfully induced. In our ANOVA model, we found a significant effect of stress in the contrast analysis ( F = 5.2, p = 0.037), indicating that CPM was affected by the stressful task. The effects on PPT could not be analyzed due to a significant carry-over effect (for PPT only). Conclusions In the present blinded crossover study, we found a significant small to medium inhibitory effect of mental stress upon the CPM of thermal pain. Implications Our results suggest that previously reported reduced inhibitory CPM in several medically unexplained syndromes with musculoskeletal pain aggravated by mental stress possibly can be related to confounding or clinically relevant stress level differences. However, the result might be modality-specific. Further studies in patients are obviously needed, and the impact of mental stress on CPM should be investigated also with other stressors.

Objectives The present study challenges chronic Whiplash Associated Disorders (WAD)-subjects to a pharmacological intravenous (i.v.) test with morphine, ketamine, and active placebo (midazolam). The aim was to describe the short-term responses to drugs and the assumed heterogeneity in the patterns of responses. We related the different responder groups to the results from psychometric tests. Methods The study includes 95 patients, all with chronic WAD and referred to our departments. They answered a questionnaire including the following psychometric instruments relevant for chronic pain: Beck Depression Inventory, Coping Strategies Questionnaire, Multidimensional Pain Inventory, Life Satisfaction Checklist, SF36 and EuroQol. The subjects also went through sessions with separate infusions of morphine (0.3 mg/kg), ketamine (0.3 mg/kg) and midazolam (0.05 mg/kg). Infusion time was 30 min followed by a 2-h post-infusion assessment. Assessments were made using a Visual Analogue Scale (VAS) for pain intensity and unpleasantness and by statements of per cent pain relieved. A categorical pain rating scale was also used. A positive response was defined as ≥50% decrease of the VAS-level on two consecutive assessment points during the test sessions, anything less was a non response. The placebo responders were defined as those with a positive response to the active placebo infusion. Results The tests were completed by 94 subjects and 26% of these were placebo responders. Among the placebo non responders, 47% responded to morphine, 41% to ketamine, 25% to both drugs and 37% to neither morphine nor ketamine (pain intensity assessments). Similar proportions were found in the assessments of pain unpleasantness and per cent pain relieved. Approximately one in four subjects (27%, pain intensity assessment) did not respond to any of the drugs tested. This relatively high proportion of non responders seemed to be worst cases in some aspects of the psychometric tests. Generally, this non responder group had a trend to score worse for most items in the psychometric tests with some reaching significance in a univariate analysis. This result was confirmed in a multivariate context, although the results indicated only small differences between the groups. All three substances showed significant pain relief compared to baseline on all assessment points. On most variables, morphine and ketamine were significantly more effective compared to the active placebo. Conclusions There are different subgroups among subjects with chronic WAD with variations in responses to i.v. morphine, ketamine, and midazolam (active placebo). Subjects with chronic WAD who did not respond to any of the drugs tested scored badly in some aspects of the psychometric instruments. Implications The present study confirms one aspect of the heterogeneity in the population with chronic WAD. The study does not elucidate precise pain mechanisms but taken together with other studies exploring other aspects, it stresses the importance of individualizing the assessment and treatment of subjects with chronic WAD. A common clinical experience is that depression, anxiety and maladaptive coping strategies often are obstacles for successful medical treatment of chronic pain. The present study supports this experience and emphasizes the need for assessment of psychometric variables when planning the treatment of chronic WAD.

Background and purpose The psychophysiological responses to and modulation of pressure pain stimulation are relatively new areas of investigation. The aims of the present study were to characterize subjective and cardiovascular (CV) responses to pressure pain stimulation, and to examine the relationship between CV responding and pain pressure pain sensitivity. Methods Thirty-nine pain-free, normotensive women were included in the study and tested during the follicular phase of their menstrual cycles. Pain threshold and tolerance were recorded at the right masseter muscle and the sternum, and visual analogue scales (VAS) were used to rate both pain intensity (the sensory dimension) and discomfort (the affective dimension). Mean arterial pressure (MAP), heart rate (HR), and facial and digital skin blood flux (SBF) were registered continuously. Results The pain threshold and tolerance were significantly higher at the sternum compared with the masseter, but the level of affective distress was higher at the masseter tolerance point. No associations emerged between pressure pain threshold and tolerance stimulation levels, and the corresponding VAS ratings. Pressure pain stimulation of the masseter induced significant increases in MAP, HR, and a decrease in digital SBF. During sternum pressure stimulation a significant change in HR and digital SBF was observed. There were no significant correlations between CV responding and pressure pain sensitivity. Conclusion Healthy women seem to display higher pressure pain sensitivity at the masseter region relative to the sternum. Pressure pain stimulation was associated with significant changes in MAP, HR, and SBF, but was not modulated by CV responses. The validity of these findings is strengthened by our control for menstrual cycle events, weekend-related changes in physiology, and CV changes during pain stimulation. Implications This study extends previous reports of SBF sensitivity to electrocutaneous pain into the field of pressure stimulation. Moreover, this study suggests that the often demonstrated association between high BP and low pain sensitivity may not apply to pressure pain specifically. Alternatively, this finding adds to the literature of gender differences in the relationship between CV responding and acute pain sensitivity in general.

Background Abnormal visceral sensory function has been demonstrated in patients with diabetes mellitus and diabetic autonomic neuropathy seems to be involved in the development and progression of gastrointestinal tract dysfunction. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in, e.g. the esophagus has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favours investigation of central pain mechanisms involved in allodynia and hyperalgesia. Hence the rationale of the presents study was to explore the nervous system by assessment of esophageal sensitivity to multimodal stimulations. Methods Throughout an euglycemic clamp, 31 healthy volunteers (age 44.3 ± 10.6 (mean ± SD) years; 11men) and 31 patients (age 46.3 ± 11.7 years; 10 men) with insulin dependent diabetes mellitus (duration 31.3 ± 13.1 years) were included in the study. By use of a multimodal oesophageal probe, sensitivity to heat, mechanical distension and electrical stimulation was assessed in the lower oesophagus. Results For heat stimulation patients had increased sensitivity in the sensory range with shorter stimulus duration until pain tolerance threshold (122 ± 3.8 sec vs. 136 ± 3.7 sec; p = 0.006) and larger area under the temperature curve (2380 ± 1847 vs. 1409 ± 1450; p = 0.03). There were no differences between groups for mechanical stimulation (maximum pressure (39 ± 57mmHg vs. 24 ± 48mmHg; p = 0.3; maximum volume 59 ± 21ml vs. 62 ± 25 ml; p = 0.56). As an overall finding, patients tolerated higher electrical stimulation intensities ( p = 0.02), dominated by discrimination in the sensory range: At sensory detection threshold (VAS1) 21.1 ± 12.4 mA vs. 16.3 ± 5.5 mA ( p = 0.03); at moderate sensation (VAS3) 27.5 ± 13.3 mA vs. 21.5 ± 5.0 mA ( p = 0.03) however at pain detection threshold (VAS5) 31.6 ± 13.1mA vs. 28.8 ± 5.2 mA; the trend was insignificant ( p = 0.3). Conclusion Patients with insulin dependent diabetes mellitus had modality-specific alterations of esophageal sensitivity. Heat stimulation activates selectively mucosal receptors whereas on the contrary electrical stimulation depolarizes the free nerve endings non-selectively. Hence, due to the different sensitivity profile, the esophageal neuropathy is most likely a result of both peripheral and central neuropathy caused by longstanding diabetic neuronal damage.

Background and aim Cutaneous inflammation induced by ultraviolet B-light (UV-B) is considered a valuable translational pain model. Until now, the development of primary hyperalgesia has been assessed predominantly in rodents, whereas porcine skin might be advantageous due to its greater homology with human skin. The aim of the present study was to investigate porcine behavioural responses to nociceptive mechanical and thermal stimulations following UV-B inflammation. Methods One skin area of 4 cm 2 in the flank of 16 male pigs of 55 ± 6 kg was irradiated by UV-B using 3xMED (Minimum Erythema Dose). Changes in pain sensitivity were assessed 24 and 48 h following irradiation via delivery of mechanical (Pressure Application Measurement device) and thermal (CO 2 laser) stimulations to the inflamed skin area and to an untreated control site. Results All animals showed higher sensitivity in the inflamed skin site 24 and 48 h following irradiation, compared to the control site ( P < 0.05). Pressure withdrawal threshold decreased in the inflamed site: 231 g (148–451) against 408g (347–684) after 24 hours and 200 g (106–293) against 656g (405–902) after 48 h. Similarly, latency to respond to the laser stimulus was lower at the inflamed site: 5 s (3–7) against 9 s (4–2) after 24h and 4 s (3–15) against 20 s (8–25) after 48 h. One and two days after irradiation, a tendency was found for an increased cutaneous mechanical pain sensitivity compared to baseline values in the site irradiated with UV-B light ( P = 0.092). Thermal sensitivity was increased within the inflamed site 24 h after irradiation with latency changing from 17s (4–25) at baseline to 5 s (3–7) at 24 h ( P =0.001). At 48 h, the response latency had not decreased any further ( P = 0.414). Conclusions Our study shows that behavioural recordings are a valid tool for the assessment of mechanical and heat sensitization following UV-B inflammation in porcine skin.

Background/aims The μ-opioid receptor (OPRM1) is the major target of endogenous opioid peptides and opioid analgesic agents. An important single nucleotide polymorphism (SNP) in this gene is the functional SNP, rs1799971, leading to a substitution of asparagine (Asn) to aspartic acid (Asp) at codon 40 in exon 1. Previous studies have suggested that this SNP may give different phenotypes in males and females. In the present study we therefore investigated whether the OPRM1 Asn40Asp SNP, grouped by gender, could predict clinical outcome regarding progression of pain intensity and disability in patients with discogenic low back pain and sciatica. Methods Patients ( n = 252) with lumbar disc herniation and sciatic pain, all European-caucasian, were recruited from Oslo University Hospital Ullevål and Haukeland University Hospital. Blood samples were drawn, genomic DNA isolated and the OPRM1 Asn40Asp SNP was detected by TaqMan methodology. Pain intensity and functional consequences were rated on a visual analogue scale (VAS), by McGill Sensory and by Oswestry Disability Index (ODI) over a 12 months period (inclusion, 6 weeks, 6 months and 12 months). Results The genotype */Asp was associated with more pain in women, but seemed to protect the men from pain after lumbar disc herniation. Wildtype Asn/Asn women and men reported similar pain ratings. Analysis of the recovery for the four groups; women Asn/Asn, women */Asp, men Asn/Asn and men */Asp, showed that the */Asp women had a significantly slower recovery, i.e., pain intensity over time than the */Asp men (VAS activity score p = 0.002, McGill sense score p = 0.021, ODI p = 0.205, rmANOVA including covariates smoke, treatment and age with p ≤ 0.1). Conclusion The present data suggest that the OPRM1 Asp variant increases the pain intensity in women, but have the opposite effect on men the first year after a disc herniation.

Background and aim Previous studies have shown that patients with chronic pain had significantly lower nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) than healthy controls. Patients with chronic pain and implanted spinal cord stimulator (SCS) system presents an opportunity to study dynamic pain sensitivity changes in a situation where patients just have been stimulated (i.e., pain-free or greatly reduced pain) and compare with the situation where patients are not stimulated (i.e., experiencing severe pain). Methods Seventeen volunteers with chronic neuropathic pain and a SCS implanted for pain relief participated in the experiment. Volunteers were asked to turn off the SCS and refrain from medication at least 8 h before the experiment. Electrical stimulation (train-of-five 1-ms pulses delivered at 200 Hz) was applied to the arc of the foot in order to elicit the NWR and electromyographic responses were recorded from tibialis anterior muscle. A staircase procedure was used to assess the NWR-T and a Visual-Analog-Scale (VAS) scale (range 0–10) was used to assess the EP-T. After the initial testing, the SCS was turned on, and thresholds were reassessed after 1 h. Paired t-tests were used to compare the thresholds before and after the SCS was turned on. All values are presented as mean ± SD. Results The NWR-T were significantly higher after the SCS was turned on (before: 16.3 ±8.1 mA; after: 19.0 ± 10.9 mA; p = 0.028). EP-T did not show any significant differences (before: 3.2 ± 1.5 mA; after: 2.9 ± 2.0 mA; p = 0.324). Conclusion Results showed a higher NWR-T after the SCS was turned on, which indicates a depression of spinal nociception. Moreover, the NWR-T was able to detect ongoing and relatively quick changes in pain sensitivity.

Background Recent developments within cognitive behavior therapy (CBT) have emphasized the utility of acceptance and mindfulness strategies, contrasting interventions focused on reduction or control of symptoms. A study of fMRI changes after CBT in females with fibromyalgia (FM) has been performed and results are presented elsewhere (under review). The aim of the present study was evaluate the effectiveness of Acceptance and Commitment Therapy (ACT)-based intervention for patient diagnosed with FM in comparison with a wait-list control Method Female patients aged 18–55 years, fulfilling the American College of Rheumatology classification criteria for FM, and with a weekly self-reported average pain intensity of >40 (VAS 0–100) were considered eligible for inclusion. Participants completed a set of questionnaires prior to treatment, immediately following the treatment and at follow 3–4 months post treatment. Primaryoutcome variable was pain disability (PDI). FIQ, SF36, SES, STAI, pain intensity, BDI, PIPS (psychological inflexibility in pain scale) were also used. The ACT-intervention consisted of twelve weekly group sessions, ten with psychologist and two with pain physician. Treatment was evaluated and mediation analyses were performed. Results Primary outcome measure (PDI): A significant improvement in pain disability for ACT in relation to the control condition, p < 0.001. Secondary outcome measures: ACT showed significant improvement in mental health quality of life, self-efficacy, depression, and anxiety. Consistent with hypotheses, ACT did not result in significant changes in either physical quality of life or pain intensity. Mediation analyses: A decrease in psychological inflexibility from pre to post assessments significantly mediated the improvement in pain disability. Conclusion The present study supports the utility of using a relatively brief ACT intervention in a group format for women diagnosed with fibromyalgia, and data suggests a mediating function on improvements in psychological flexibility.

Background/aims The molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain. Methods We subjected wild-type ( wt ), sortilin knockout ( Sort1 -/- ) and SorCS2 knockout ( SorCS2 -/- ) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold. Results As previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia. Conclusion We hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.

Background/aim The aim of the current study was to assess the neuropathic component of persistent post-surgical pain (PPSP) following eleven types of surgery. Methods We performed a systematic PubMed, CENTRAL and EMBASE search to identify studies on PPSP following (i) thoracic surgery, (ii) breast surgery, (iii) groin hernia repair, (iv) prostatectomy, (v) major abdominal surgery, (vi) gynecologic surgery, (vii) iliac crest bone harvest, (viii) total hip arthroplasty (THA) or knee arthroplasty (TKA), (ix) varicose vein stripping or ablation, (x) mandibular sagittal split osteotomy and (xi) donor nephrectomy, and assessed the prevalence of Probable/Definite neuropathic pain using the recently published neuropathic pain probability grading criteria [1]. Results We included 291 relevant papers. Surgeries performed in the thoracic/breast area resulted in similarly high median PPSP prevalence of about 30–35%; bone and joint surgeries resulted in similar PPSP prevalence of about 20%; and surgeries on visceral organs resulted in lower PPSP prevalence of 10–14%. The reported ranges of PPSP prevalence were very wide, between 0 and 91%. The prevalence of Probable/Definite neuropathic pain among patients with PPSP was about 65% after thoracic and breast surgeries, about 32% after groin hernia repair and gynecologic surgery, and between 9 and 16% after bone and joint surgeries such as iliac crest bone harvest and THA/TKA. In varicose vein surgeries and mandibular sagittal split osteotomies more research is needed to investigate the contribution of neuropathic pain mechanisms. Conclusion PPSP after different surgeries is reported to be common and often neuropathic. This systematic review of the literature showed that reported PPSP prevalences range widely among studies, and only a minority of studies used methodology that enabled the estimation of Probable/Definite neuropathic pain prevalence.

Background/aims Despite multiple efforts to improve practice, pain is prevalent in many hospital settings causing unnecessary complications and suffering. The aim of the study was to explore the epidemiology of pain in a university hospital in Iceland. Methods A point prevalence study was conducted in 23 departments in medical and surgical services in a 650 bed university hospital in January 2011. Data was collected from medical charts and with a questionnaire (APS-POQ-R) assessing pain severity and quality of pain management. Participants had to be 18 years or older, hospitalized for at least 24 h, speak Icelandic, alert, and able to participate. Results Of the 369 participants the mean (SD) age was 67.9 (17.6) years (range 18–100) and gender proportions were equal. Response rate was 80%. Of patients in pain (scoring ≥1 on a 0–10 scale) the mean (SD) worst pain severity was 5.6 (2.5). Total pain prevalence was 80.4%, but of patients in pain 36.5% had mild (1–4) pain, 22.6% moderate (5–6) and 40.9% had severe (7–10) pain. The mean (SD) proportion of time spent in severe pain was 25.9% (27.0%). Pain was both more prevalent, [χ 2 (1, N = 367) = 7.05, p = 0.008] and severe [ t (365) =−4.16, p = 0.000] in women compared to men. Similarly, pain was more prevalent [χ 2 (1, N= 368) = 9.71, p = 0.002] and severe [ t (216,2) =−3.18, p = 0.002] in surgical services compared to medical. Worst pain severity was weakly negatively associated with age [ r (369) =−0.23, p = 0.000]. Worst pain severity was higher in patients receiving pain medications [ t (357) =−9.84, p = 0.000] and in patients using non-pharmacological methods to treat their pain [ t (311.7) =−5.76, p = 0.000]. Conclusions Pain was prevalent in the hospital and an unsatisfactory proportion of patients experienced moderate to severe pain. The quality of pain management in the hospital needs to be improved. Further studies are needed to test and evaluate the efficacy and effectiveness of interventions aimed at advancing pain practice in the hospital setting.

Background/aims Tail docking neonatal piglets remains a controversial animal welfare issue. Although banned in the UK, it is widely practiced in many countries as a safeguard against tail biting among pigs reared in intensive systems. Concerns exist whether tail docking can induce chronic pain in later life. This preliminary study examined the effects of partial tail amputation on activating transcription factor 3 (ATF3), a marker of peripheral nerve injury and regeneration and NMDA-glutamate receptor NR2B subunit which participates in the mediation of chronic pain. Methods Procedures were performed according to the ethical guidelines for the study of experimental pain in animals. Six piglets (2–3 days old) were tail-docked (a portion of the tail amputated with sterile surgical cutters), six piglets (2–3 days old) were sham-docked. Three animals from each treatment were euthanised 7 and 56 days post-amputation. Coccygeal dorsal root ganglia (DRG) and spinal cord were collected post-mortem for immunohistochemistry. Results ATF3 immunoreactivity (IR) was significantly increased ( p <0.05) in the DRG neurons from tail-docked piglets 7 days after tail amputation, compared with sham-docked piglets. ATF3-IR was not different in sham and tail-docked piglets 56 days post amputation. NR2B-IR was significantly increased ( p < 0.05) in dorsal horn neurons in tail-docked piglets compared with intact piglets 7 days after docking. There was no difference in NR2B-IR in neurons 56 days post amputation, compared with intact piglets. Conclusions Increased ATF3 and NR2B-IR 7 days after tail-docking suggests that injury to the peripheral nerves in the tail was sufficient to trigger neuronal regeneration and altered dorsal horn signaling respectively, however the effects of tail-docking on neuronal regeneration and nociceptive signaling were relatively short lasting. Tail-docking neonatal piglets does not cause sustained changes in ATF3, which might suggest ongoing nerve fibre damage and NR2B which might be implicated in chronic pain.

Background Long-term or chronic pain represents a major health problem and is associated with significant socio-economic costs. During injury, pain can be dissociated from its normal physiological role. It can persist for a longer period of time, even after the primary noxious stimulus has more or less subsided. Analgesic drugs, with predominant neuronal sites of actions, seem to be relatively ineffective. Chronic pain is probably partly a consequence of ongoing neuroinflammation. The mechanisms behind these phenomena, and how the neuronal and non-neuronal activities evoked by painful stimuli and inflammation are processed in the brain and throughout the CNS, are not well understood. Methods Primary cultures, calcium imaging, immunocyto-chemistry, Western blotting, cytokine release. Results Following pain stimuli increased activity of inflammatory receptors and shifts in intra- and extracellular ion concentrations occur within the CNS. One signalling pathway in astrocytes propagates Ca 2+ waves, which initially decrease and then increase in form of oscillations in the astrocyte networks. This causes dysfunction in the astrocytic Ca 2+ signalling resulting in down-regulation of Na + transporters, and increased release of pro-inflammatory cytokines. The neurons will then increase their excitability and, hypothetically, also increase the sensitivity for development or potentiation of neuropathic pain states. Low-dose of potential anti-inflammatory and analgesic drugs restore the disturbed astrocytic Ca 2+ signalling, and modulate the activity of inflammatory receptors and Na + /K + -ATPase. We recently report, in patients with long-term pain, changes in neurotrophic factors and pro-inflammatory cytokines in blood and CSF. Conclusions Dysfunction in downregulation of Na + transporters, changed Ca 2+ signalling in the astrocyte networks and release of cytokines from glial cells can lead to pathogenic chronic neuroinflammation. Modulation of the Na + /K + -ATPase activity and restoration with anti-inflammatory substances will lead to a balance between inflammatory and anti-inflammatory mediators in inflammatory reactive cells. The pharmacological treatment of today is directed towards neuronal over-excitability, unfortunately with less success. A novel pharmacological treatment strategy would thus be directed towards the activated astrocytes and microglial cells, being the source of the neuroinflammation. This will be an important knowledge for treatment in clinical therapy.

Background/aims Elevated concentrations of nitric oxide (NO) and glutamate (Glu) in the trigeminal ganglion (TG) may contribute to the development and maintenance of migraine headache. The role of satellite glial cells (SGC) and their pattern of substance release in relation to the pathophysiology of migraine are currently under investigation. In the present study, we investigated the release of NO from isolated trigeminal SGCs and its modulation by Glu. Methods SGCs from the TG of adult male Sprague-Dawley rats ( n = 8) were isolated and maintained in culture until used. SGCs were treated with graded concentrations of Glu (0, 10, 100, 1000 μM) and samples were withdrawn after 48 h of incubation. In subsequent experiments, SGCs were treated with vehicle medium, 10 μM forskolin (FSK) alone, or 10 μM FSK in conjunction with 100 μM Glu and incubated for 48 h. The NO concentration was determined using the Griess Reagent System and data was subjected to a one-way repeated measures ANOVA analysis, where p <0.05 was considered statistically significant. All experimental procedures were performed at minimum in triplicate. Results The concentration of NO was 3.59 ± 0.04 M under baseline conditions. Application of 10 or 100 μM Glu resulted in a significant drop in NO concentration (2.92 ± 0.017 μM and 2.83 ± 0.012 M, respectively) compared to baseline, whereas treatment with 1000 μM Glu did not significantly alter NO release. Treatment of SGCs with 10 μM FSK significantly increased NO release (to 125.94 ± 3.90% of baseline) compared to baseline. Coapplication of 10 M FSK with 100 M Glu significantly decreased FSK-induced NO release (83.73 ± 2.29% of baseline), compared to both FSK-mediated NO release and baseline levels. Conclusion These findings suggest that one mechanism by which SGCs protect the TG from elevated Glu concentrations that may occur in response to prolonged noxious stimulation is to reduce the release of NO.

Background and aim Tail docking has been suggested as an animal model of neuropathy and pain based on findings of relations between the degree of neuroma formation and the docking length. We examined effects of docking length on behaviour of piglets during and 6 h after tail docking. Methods Piglets were tail docked 2–4 d post-partum. We used 53 piglets and four treatments: intact (I), removal of either 25 (Q), 50 (H) or 75% (T) of the tail. The piglets were kept with sow and littermates under production conditions, and docked using a gas-heated instrument. Behaviour was observed during docking and for the following 6 h. Results Tail docking led to behavioural changes, the magnitude of which to some extend depended on docking length. Increased docking length led to increased intra-procedural vocalization score (0, 0.6 ± 0.2, 1.4 ± 0.2 and 1.4 ± 0.2 for I, Q, H and T, respectively, P <0.001). In the initial 6h, increased docking length led to increased time spent in the heated creep area (2 ± 1%, 15 ± 6%, 18±8% and 30±6% for I, Q, H and T, respectively; P <0.05). Piglet posture was affected as well, showing that increased docking length led to decreased lying (71 ± 2%, 68 ± 2%, 61 ± 2% and 61 ± 2% for I, Q, H and T, respectively, P <0.01) and increased time spent active (24 ± 2%, 23 ± 2%, 32 ± 2% and 30 ± 3% for I, Q, H and T, respectively, P < 0.05). Pain specific behaviours such as trembling or tail flicking were registered and occurred in 5 ± 1% and 9 ± 1% of observations. However, no effects of docking length could be shown. Conclusions Piglets responded behaviourally to tail docking. Increasing docking length led to increased pain responses such as intra-procedural vocalizations, hiding behaviour and reduced rest, indicative of increased pain. These results confirm earlier reports suggesting that tail docking might be suitable as an animal model for neuropathy and pain.

Introduction An unmet medical need for more effective therapies of neuropathic pain exits. Here modulation of the glutaminergic system represents an unexplored possibility. Down-regulation ofglutamate transporters potentiates pain transmission by delaying the removal of glutamate from the synapse. In the spinal cord, glutamate transporter 1 (GLT–1) is responsible for more than 90% of the glutamate uptake. Ceftriaxone, a β-lactam, is believed to induce the expression of GLT–1 through the transcriptional factor (NF-ºB) pathway, which results in induced promoter activity and thereby increased synthesis of GLT-1 protein. Objectives To evaluate the analgesic effect of ceftriaxone in the Chronic Constriction Injury (CCI) rat model of neuropathic pain and to investigate the pharmacodynamics of ceftriaxone in a chronic dosing regime. Methods In CCI rats, mechanical and thermal hypersensitivity, were determined with von Frey filaments and Hargreaves test, respectively. Groups of rats received ceftriaxone (200, 300 or 400 mg/kg, i.p.) once daily in 7–19 days and the control groups received vehicle. Results From a total of 24 CCI operated rats, 16 rats developed both mechanical (withdrawal threshold ≤3g) and thermal hypersensitivity (latency threshold ≤13 s.). Ceftriaxone alleviated mechanical allodynia and thermal hyperalgesia in CCI operated. Daily dosing of ceftriaxone 200, 300 and 400 mg/kg reached the same withdrawal threshold levels as before the CCI surgery, after 18, 12 and 7 days, respectively. This indicates that the dynamic effect of ceftriaxone is not only dependent of the dose, but also the duration of administration. Thus, it seems that dose exposure above a certain threshold is necessary to induce protein synthesis. Conclusion The CCI model is a useful model to evaluate the anti-nociceptive effects of ceftriaxone. Increased dose do not only elevate effect magnitude but also the rate of with which the effect appears.

Background In recent years only few novel drugs targeting visceral pain have been developed. This lack of success may be explained by animal models having poor predictive value. To increase the success of translating results from animals to humans there is a demand for comparable test models. The aim was to establish a comparable and reliable translational model to evoke mechanical rectal pain in rats and humans. Methods Mechanical rectal rapid balloon distension was done on two different days in 12 rats (separated by 24.3 ± 7.1 days) and 18 humans (separated by 9.3 ± 1.3 days). Evoked potentials were recorded from permanently implanted skull-electrodes in rats, at stimulation pressure of 80 mmHg and duration of 100 ms. In human surface electrodes and individualized pressure, corresponding to the pain detection threshold, lasting 150 ms, were used. Within- and between days reproducibility were assessed in terms of latencies, amplitudes and frequency content. Results In both rats and humans evoked potentials with tri-phasic morphology were recorded. No differences in latencies, amplitudes and power distribution were seen within or between days (all F ≤ 2.0; all P ≥ 0.2). The analyses of the EPs revealed peak-to-peak amplitude as the most reproducible parameter within (ICC ≥ 0.84) and between (ICC ≥ 0.70) days, seen across both species. The spectral analyses showed that the EEG power was distributed mainly in the delta and theta bands. The main power in rats was contained in the theta band (45%), whereas humans had the predominant power in the delta band (46%). Conclusion A unique visceral translational platform was established to reliably assess neurophysiologic response to rapid balloon distension in rats and humans. The model provides an approach to study basic and clinical pain as well as pharmacological intervention.

Background/aims Analgesic effects of BoNTA develop within few hours in animal studies and within days in human studies. We have previously shown that BoNTA can block glutamate-induced mechanical sensitization and neurogenic vasodilation in rat temporalis muscle within 3 h. The present translational study was designed to explore the time-course of analgesic effects of BoNTA on pain, sensitization and vasomotor responses in a glutamateevoked human pain model. Methods BoNTA (5U) and saline were injected (30 min interval) into the left and right temporalis muscles of 12 healthy males (24.2° 2 years). Pressure pain threshold (PPT), skin temperature (thermo camera) and tissue perfusion (laser Doppler flowmetry) were measured every hour for 3 h. Afterwards, subjects received an intramuscular injection of glutamate (1M– 0.2 mL) into the left and right temporalis muscles. Pain intensity (VAS) was recorded for 10 min after injection and pain distribution was then mapped. PPT was measured at 15 and 30 min following the glutamate injections, while skin temperature and tissue perfusion were recorded at 5, 15 and 30 min. Results This preliminary data showed that BoNTA significantly reduced glutamate-evoked peak pain intensity compared with saline ( P = 0.042). Expansion of pain area was also smaller in the muscles pretreated with BoNTA ( P = 0.045). Glutamate-induced vasomotor reactions (elevated skin temperature and tissue perfusion) showed a tendency to decline in BoNTA-pretreated muscles. A similar pattern was seen in terms ofmuscle sensitivity with higher PPT values in BoNTA-pretreated muscles. Conclusions BoNTA induced a direct analgesic effect withi 3 h of its injection into the temporalis muscle. This phenomenon, at least in part, might be through BoNTA actions on nociceptors. Present data also indicated that BoNTA attenuated glutamateinduced muscle sensitization and vasomotor reactions. This finding may suggest additional effects of BoNTA on the pattern of release of substances which are involved in pain pathways.

Background/aims Brief noxious heat stimuli activate Aδ and C fibers, and contact heat evoked potentials (CHEPs) can be recorded from the scalp. Under standard conditions, late responses related to AS fibers can be recorded. This study examines C-fiber responses to contact heat stimuli. Methods A preferential A-fiber blockade by compression to the superficial radial nerve was applied in 22 healthy subjects. Quality and intensity of heat evoked pain (NRS, 0–10), and CHEPs were examined at baseline, during nerve compression, and during further nerve compression with topical capsaicin (5%). Results During the A-fiber blockade, 3 subjects had CHEPs with latencies below 400 ms, 8 subjects within 400–800 ms and 6 subjects later than 800 ms. Pain intensity to contact heat stimuli was reduced and fewer subjects reported the heat stimuli as stinging. Following acute capsaicin application, ultralate CHEPs with latencies >800 ms could be recorded in 13 subjects, pain intensity to the contact heat stimuli was increased ( p <0.01) and more subjects reported the heat stimuli as being more warm/hot-burning. Conclusion The results indicate that following a compression to the superficial radial nerve, CHEPs compatible within complete A fibers or C fibers were recorded. Following sensitization with capsaicin, C-fiber responses were recorded in 62% of subjects.

Objective To test the effect of different neck training methods on motor evoked potentials (MEPs) from the trapezius muscle. We hypothesized that training of the trapezius muscle would significantly increase MEPs, indicating facilitation of the corticomotor pathways. Additional experiments investigated the influence of muscle strength, muscle fatigue, and correlations between MEP amplitudes and behavioral aspects of motor learning. Methods Transcranial magnetic stimulation (TMS) was used to elicit MEPs from the trapezius muscle and the abductor pollicis brevis (APB) muscle in 60 healthy subjects in three conditions: (1) specific trapezius training, (2) coordination training of the neck, and (3) no training. Results Specific training yielded an increase in MEPs 1 h ( p = 0.001) and 7 days ( p = 0.001) after training compared with baseline; no significant changes were seen after coordination training or no training. MEPs from the APB muscle did not change over time in any of the conditions. Muscle strength increased by 8% after specific training, but no subjective or objective measures of fatigue were observed. Conclusions The results showed that only specific training significantly increased trapezius MEPs for up to 7 days, indicating facilitation of the corticomotor pathways. These findings may help improve the future clinical management of neck pain.

Aim of investigation Persistent postoperative pain of some extent is seen in about 20% of patients after surgical operations, while 80% heal without chronic pain. The type of chronic pain that arises is mainly neuropathic, and is suggested to be in part regulated by genetic factors. In order to study the possible involvement of some candidate genes suggested to be involved in the processing of pain (BDNF, CACNA2D2, ORPM1, GRIK 3, GCH1 and TNF- α ), we performed a genetic association study in a well characterized clinical material of patients that had undergone surgery for inguinal hernia ( n = 189). Of those 94 had developed a persistent postoperative pain state when investigated 2–3 years following the operation. The control group ( n = 95) had undergone the same surgical procedure, and were pain free at follow up. Methods Genomic DNA was extracted from blood samples and genotyped by the Handy Bio-strand method and the TaqMan assay. Results The patients with persistent postoperative pain that had homozygous SNP in the TNF- α gene displayed increased risk of persistent postoperative pain with an odds risk of 2.42, compared the pain free controls. None of the other of the investigated genes were associated with significant risk of development of chronic pain following surgery. Conclusion The expression of TNF- α shows a significant impact on the risk of developing chronic pain after surgery. Further experimental and clinical studies are needed in order to fine map the TNF- α effect and to address underlying mechanisms.

Background/aims Chronic pain is frequent after thoracotomy (Wildgaard et al., 2009; Guastella et al., 2011). According to a recent Danish study with a follow-up period of 22 months, 33% of the patients developed pain after thoracotomy, and 4–12% of the patients experienced severe pain (Wildgaard et al., 2011). The mechanisms underlying chronic pain after surgery are not fully known, but several risk factors have been identified, e.g. intraoperative nerve damage and acute postoperative pain (Kehlet et al., 2006). A few studies have suggested a correlation between nerve damage during surgery and the development of pain after thoracotomy (Benedetti et al., 1997, 1998; Rogers et al., 2002). We plan to investigate if intraoperative nerve damage is responsible for the development of pain and sensory abnormalities after thoracotomy. Methods Sixty individuals with normal sensibility on the thorax will be included preoperatively. Motor and sensory nerve conduction studies (NCS) will be performed during surgery. Post-surgical follow-up with questionnaires and bilaterally Quantitative Sensory Testing (QST) on the thorax will be performed according to the protocol of the German Research Network on Neuropathic Pain (DFNS). Before implementing the neurophysiological measurements in humans, they have been tested in pigs. Results Neurophysiological measurements in pigs have shown that it is possible to do NCSs on both motor and sensory intercostal nerves, suggesting that measurements are possible in humans. Inclusion of patients is pending. Conclusion The preliminary results will be presented at the congress.

Background/aims Quantitative sensory testing (QST) is a reference method in characterization of neuropathic pain components. Variability data on thermal thresholds have been presented for a number of diseases, but not for patients with persistent post-surgical pain. Thus, the objectives of the present study were to assess the day-to-day variation, but also topographic variability in thermal threshold assessments in post-thoracotomy pain syndrome (PTPS) patients. The variability in thermal thresholds between pre-specified sites, on the surgical and the non-surgical side were compared to each other and to the area of maximum pain. Patients and methods Fourteen PTPS patients were included. Dynamic sensory mapping was performed with a 25 °C metal roller (cool). Within the area of cool sensory dysfunction on the surgical side (thorax), 4 peripheral locations were marked including the maximum pain area. Similarly 4 identical peripheral but contralateral sites on the non-surgical side were also marked. Warmth detection threshold (WDT), cool detection threshold (CDT) and heat pain threshold (HPT) were assessed on day1 and day2, separated by 12 days for all marked locations. Results Comparisons of test-retest thermal assessments (day 1–day 2), did not demonstrate any significant intra-side differences. The 99% confidence intervals for WDT ranged between 32.6 and 46.6°C, for CDT between 20.2–30.5 °C and for HPT between 37.9–51.5 °C. Within-patient and between-patient variances consisted of 5 to 28% and 73 to 95%, respectively of the total variance. Side-to-side comparisons displayed higher thresholds on the surgical side Conclusion In patients with PTPS, different statistical methods indicated an excessively high variability in thermal thresholds, in particular for between-patient variance. This may suggest an advantage in using patients as ‘self-controls’ for assessment of thermal thresholds. However, due to the low within-patient variance, our study could still demonstrate highly significantly increases in thermal detection thresholds, within the area of cool sensory dysfunction, on the surgical side compared to the contralateral side. Also, static and dynamic assessments of thermal perception seem to indicate considerable wide-spread loco-regional changes on the side of surgery, an important finding when deciding where to assess thermal thresholds.

Background Persistent pain after breast cancer treatment (PPBCT) is a considerable clinical problem affecting between 25 and 60% of breast cancer survivors [1]. Several risk factors have been proposed, among them nerve damage caused by adjuvant treatment [2]. Taxanes used in adjuvant therapy for breast cancer are neurotoxic, and thereby being a potential risk factor for PPBCT and sensory disturbances. However, the long term influence of taxanes on PPBCT is not well documented. Thus, the aim of this study was therefore to compare a nationwide cohort treated with cyclophosphamide and epirubicin + docetaxel (CE + T) versus a nationwide cohort treated with cyclophosphamide, epirubicin and fluoruracil (CEF), in order to assess differences in reporting of PPBCT, sensory disturbances in surgical area, symmetric peripheral sensory disturbances, and functional impairment. Methods A comparative nationwide cross-sectional questionnaire study on two cohorts treated with CEF respectively CE + T, based on the Danish Breast Cancer Cooperative Groups database. Inclusion criteria were identical i both cohorts: women treated with adjuvant chemotherapy for primary breast cancer, age 18–69 years, without recurrence. Exclusion criteria: bilateral or previous breast surgery, including reconstructive surgery. The same questionnaire [1] was used for both cohorts and contained detailed questions regarding pain intensity and frequency and sensory disturbances in the breast area, side of chest, axilla and arm, bilateral peripheral sensory disturbances in the hands and feet, and questions regarding daily activities. Results 1241 patients treated with CEF in 2005-2006 and 1652 patients treated with CE + T in 2007–2008 were included. 664 (54%) with CEF and 861 (53%) patients with CE+T reported PPBCT. In the multivariate analysis including available risk factors, CE + T did not increase risk of PPBCT, adjusted OR 0.95 (95%C10.81–1.11), p = 0.52, compared to CEF. Patients treated with CE + T had a lower risk of sensory disturbances in the area of surgery compared with CEF, adjusted OR 0.75 (95%C1 0.62–0.90), p = 0.002. More CE+T patients reported peripheral sensory disturbances in the hands, adjusted OR 1.56 (95%C11.27–1.92), p < 0.0001, and in the feet, adjusted OR 2.0 (95%C1 1.66–2.42), p < 0.0001, compared to CEF. There was no difference in functional impairment ( p = 0.62). Conclusion Docetaxcel as adjuvant treatment for breast cancer does not increase the risk of PPBCT, sensory disturbances in the surgical area or functional impairment, but increase the risk for peripheral sensory disturbances.

Background/aims Abnormal visceral sensory function in diabetes mellitus (DM) leads to neuronal changes in the enteric, peripheral and/or central nervous system (CNS). To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials (EPs) and dipolar source modelling. Methods Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multi-channel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled by use of Brain Electrical Source Analysis (BESA). Results Diabetic patients had higher stimulus intensities to evoke painful sensation ( P <0.001), longer latencies of N2 and P2 components (both P <0.001), lower amplitudes of P1–N2 and N2–P2 complexes ( P <0.001; P = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization ( P = 0.002). Symptom score index was negatively correlated to the depth of insular activity ( P = 0.004) and positively correlated to insular dipole strength ( P = 0.03). Conclusion DM patients show neuroplastic changes in the central nervous system. The role of abnormal insular processing may explain the development and persistence of upper GI-symptoms related to DAN. This enhanced understanding of DAN may have clinical and therapeutical implications.

Background/aims Exercise and experimental pain is known to cause an acute decrease of the pain sensitivity. Assessment of pain inhibitory mechanisms is often done by paradigms of exercise and experimental pain in both healthy subjects and pain patients. It is currently unknown whether pain and different types of exercise has similar effects on pain sensitivity. The aim of the present study was to investigate the effects of experimental pain and different types of exercise on deep tissue pain tolerance in healthy subjects. Methods On two separate days fifty-four healthy subjects (23 females, 33.8 ± 15.0 years) were assigned in random order to cold pressor tests (ice water at 1–2°C; 120 s duration) for the dominant hand and foot, bicycling exercises (100 W and 200 W; 20 min duration), and isometric contraction exercises (30% and 60% of maximal voluntary contraction, MVC; 180 s duration) of the dominant quadriceps and biceps brachii muscles. Before, immediately after, and 10 min after cold pressor tests and exercises, pressure pain tolerance (PTT) were assessed with computerized cuff-algometry at the non-dominant lower-leg and upper arm. Subjects reaching maximum stimulation intensity at baseline were excluded from the analysis. PTTs were analysed with repeated measures ANOVA and multiple comparisons. Results Immediately and 10 min after the cold pressor test in the dominant hand and foot significantly increased PTTs were found at the non-dominant upper arm and lower leg ( P < 0.05). Both intensities of dominant biceps brachii isometric contractions produced a significant increase in the PTT at the non-dominant lower leg immediately after and 10 min after contractions ( P < 0.05). After the 30% dominant quadriceps isometric contraction the PTT at the non-dominant lower leg was significantly increased ( P < 0.05). Conclusion Cold pressor pain produced a contralateral and extrasegmental increase in deep tissue pain tolerance. Isometric arm exercise produced an extrasegmental increase in pain tolerance, whereas isometric leg contractions produced a contralateral effect. Aerobic exercise had no effect on pain tolerance. Thus, exercise and pain related inhibitory effects were not comparable. Acknowledgment/disclosures H.B. Madsen was supported by grants from the philanthropic foundation TrygFonden (7-11-0990), The Danish Rheumatism Association 8R95-A1871), The Research Foundation of the Danish Physiotherapy Association and The Fund for Physiotherapy in Private Practice.

Background/aims The ultraviolet B (UVB) inflammatory pain model is often used to induce a steady hyperalgesic area in human skin. UVB causes a well-described erythema, developing maximal response within about 24 h. The aim of the present study was to investigate if cutaneous UVB irradiation can influence both superficial and deep-tissue mechanical pain thresholds in the site of irradiation and in the surrounding area. Methods An area of 3 cm × 4 cm, located on the low back of 16 healthy volunteers, was irradiated by UVB (Medlight, Germany; 3xMED: Minimal Erythema Dose). The degree of inflammation was detected by measuring superficial blood flow before and after irradiation, inside and outside the stimulated area. Applying quantitative sensory assessments, mechanical pain threshold changes were detected one day after irradiation, within and outside of the irradiated area. Sensitivity to cutaneous mechanical stimuli was assessed using pin prick and deep-tissue pressure pain thresholds were evaluated on 12 spots (4 within and 8 outside, 1.5 cm distant from the irradiated area) by a computer-controlled pressure algometer (Aalborg University, Denmark; 1.0 cm 2 flat probe, 0.5 cm 2 flat probe and a V-shaped probe with a contact surface of 0.03 cm 2 ). Results 24 h after exposure, the irradiated skin showed clear erythema with a boundary matching the irradiated area and a statistically significant increase in cutaneous blood flow ( P < 0.001) compared with baseline assessment. Cutaneous pin prick pain thresholds and deep-tissue pressure pain thresholds (all probes) were significantly decreased inside and outside the irradiated area ( P < 0.05). Conclusions Cutaneous UVB irradiation reduces mechanical pain thresholds to pin-prick and pressure stimulation which may indicate allodynic responses in both the skin and in deep-tissues. Expansion of the responses to areas outside the irradiated zone confirmed the presence of secondary hyperalgesia to mechanical stimuli.

Background/aims Muscular pain often impairs masticatory function in Temporomandibular disorder patients. The specific aim of this study was to investigate how the bite force during mastication is influenced by experimental muscle pain caused by infusion of glutamate into the masseter muscle. Methods 12 healthy adults participated, after providing informed consent. Customized metal frames of the intraoral bite force sensor were manufactured for all subjects, and placed on their preferred chewing side. To induce experimental pain, a sterile solution of glutamate (0.5 M) was infused into the posterior part of the masseter muscle. Isotonic saline (0.9%) was infused as a control (randomized, cross-over design). During chewing three different kinds of test food (two different size carrots and gummy), bite force, electromyographic (EMG) activity of bilateral masseter muscle and anterior temporalis muscle were recorded. The first and last five masticatory cycles were used for analyses. The outcome parameters were as follows; Visual Analog Scale (VAS) for pain, impulse and duration from the bite force signal, duration and amplitude of EMG. Three-way ANOVAs with food (3 levels), sessions (5 levels: baseline, during glutamate, baseline 2, during isotonic saline, follow-up), cycles (2 × 5 levels) were carried out. Results Glutamate caused moderate levels of pain (mean VAS: 2.4 ± 0.9) whereas isotonic saline only caused low levels of pain (Mean VAS: 0.7 ± 0.5). The ANOVA of impulse data, as well as most EMG data, demonstrated a significant effect of session. Post hoc tests showed significantly higher impulse values of both the first and last five cycles in the glutamate session compared to baseline whereas the EMG activity was significantly decreased ( P < 0.05). Conclusion Surprisingly, experimental pain induced by glutamate increased the bite force during mastication coupled with a decrease in EMG activity. This indicates a major reorganization of the motor control during painful mastication.

Background/aims The nociceptive withdrawal reflex (NWR) is a robust measure of nociception highly correlated with subjective pain and several studies indicate that identification of reflex thresholds may be a valuable objective tool during diagnosis of chronic pain conditions related to central sensitisation. The NWR involves complex muscle synergies but most methodologies for assessment of human withdrawal reflexes evaluates surface electromyography (sEMG) measured over just one muscle and does not consider the possible interference of crosstalk from adjacent muscles. This study investigated if standardised reflex thresholds are robust with respect to crosstalk. Methods Reflexes were elicited by electrical stimulation at the sole of the foot and measured using sEMG and intramuscular electromyography (iEMG) from the tibialis anterior and soleus muscles in 15 healthy subjects. 489 sEMG recordings were evaluated using a standardised reflex threshold parameter (interval peak z-score) proposed by Rhudy and France [1] to detect occurring reflexes. The outcome of this standardised reflex detection were compared to two different visual evaluations: (1) assessing only sEMG and (2) assessing both sEMG and iEMG (enabling distinction between genuine reflexes and crosstalk) for the production of two respective ROC-curves. Results The first ROC-curve indicated that interval peak z-score allows reflex detection with high accuracy and has an optimal threshold around z = 12. However, the second ROC-curve based on evaluation 2 revealed that many recordings identified as reflexes were incorrectly categorised reflecting crosstalk. Crosstalk did severely reduce the accuracy of the performed reflex detection – a z -score threshold of 12 was found associated with an extremely poor specificity (0.26). Conclusion Crosstalk may severely reduce the accuracy of standardised reflex threshold assessment methodologies. Use of standard sEMG for reflex recording may cause an alarmingly low specificity of reflex detection and should be avoided whenever the presence crosstalk is suspected.

Background/aims Descending modulation of the nociceptive system has proven to be pronounced in healthy humans. The descending modulation can be activated by rather distinct methods such as strong tonic painful stimulation or changes in the cognitive state. The extent of descending modulation on spinal pain processing remains unclear. Therefore, we assessed simultaneous cognitive modulation of spinal and cortical processing of experimental pain. Methods Painful (1.7 × pain threshold (PT)) and non-painful (0.5 × PT) electrical stimulation was applied to the sole of the foot of 9 healthy subjects. Cortical activity was recorded by EEG from the vertex and the nociceptive withdrawal reflex (NWR) was recorded from the tibialis anterior muscle. Stimulations were applied during the Spatial Attention Task, where the subject was asked to indicate the direction of arrows presented in a computer screen, and when the subjects were relaxed. The subject was asked to rate the average pain intensity after 30 stimuli. A total of 240 stimuli were applied. Results The amplitude of the EEG P100 ( p < 0.001), P300 ( p = 0.019) peaks, the pain intensity ( p < 0.001) and the NWR ( p < 0.05) were all significantly higher when noxious stimulation was applied than when non-noxious stimuli were applied. The spatial attention task did not significantly modulate the amplitude of the P100 ( p = 0.083), the P300 ( p = 0.804) peaks, and the pain intensity ( p = 0.139), but the NWR were significantly lower during the Spatial Attention Task ( p = 0.042). Conclusion The results indicated that attracting the attention of the subjects to a task of spatial discrimination evoked a descending modulation affecting nociceptive processing at the spinal level. Still pain perception and late components of the vertex EEG were not significantly altered by the spatial attention task.

Background/aims Previous studies have focused on the effect of negative emotions generated by music, pictures or odours on pain perception. This study tested whether emotionally loaded visual and gustatory stimuli could influence experimental tonic jaw muscle pain in healthy subjects. Methods 32 healthy subjects (16 men, 16 women; 18–39 years old) participated. In two sessions experimental jaw muscle pain was evoked by injection of 0.2 ml hypertonic saline into the masseter muscle. In the first session with each injection an emotion (positive, negative or neutral) was generated by visual stimuli (pictures taken from International Affective Picture System). In the second session, emotions were generated by gustatory stimuli (75% sucrose = sweet, 0.1% quinine = bitter, or tasteless gelatine). The participants continuously rated pain intensity (electronic visual analogue scale – VAS) as well as mood and unpleasantness/pleasantness of the conditioning stimuli (visual/ gustatory). Results and conclusion Hypertonic saline evoked moderate levels of pain in all subjects (mean peak VAS = 5.2 ± 2.4). During conditioning with negatively loaded pictures VAS pain scores were increased (19.3%) compared with neutral ( p = 0.03) and positive emotions ( p = 0.001). There was a linear relation between negative emotions and VAS pain scores ( r = 0.40, p = 0.02). Although there was a tendency, no significant effect was observed during positive pictures in comparison with neutrals ( p = 0.1). Surprisingly no effect on VAS pain scores was observed during neither negative ( p = 0.1) nor positive ( p = 0.2) gustatory stimuli. This may be due to failure of the gustatory stimuli to generate a change in emotions. These results suggest that not all conditioning stimuli are potent modifiers of emotions, which seem to be a prerequisite for effects on pain perception.

Background/aims Being able to modulate pain through visual input raises the possibility that visually distorting body size also will reduce pain. The aim of the present study was to investigate whether experimental cold/heat pain could be modulated through a visual illusion of an increased/decreased hand size and whether pain perception correlated with the perceived sense of control of movement. Methods 20 healthy right-handed volunteers were recruited. Hand sizes were modulated through an AR setting designed to act as a mirror. Four conditions were included: (1) No AR setting; (2) left/right hands were the same size; (3) left hand enlarged; (4) left hand decreased. Pain thresholds (PT) for both hands were alternately assessed using two thermodes, placed on each palmar side of the hands. After each condition subjects rated the following statement: “I could control the movements of my left/right hand”. Results Heat pain : no main effect for conditions or hands (left/right). Cold pain : Significant main effects for conditions, but not for hands – condition (2) is significantly more painful than all conditions. Control of movements when the left hand is stimulated : the more control subjects have of right hand in condition (4), the higher the cold PT for the left hand in conditions (1) and (2). Control of movements when the right hand is stimulated : the more control subjects have of the right hand in condition (4), the higher the heat PT in the right hand for condition (2). Conclusions Visual illusions can modulate pain, however the modulating factors do not only depend on the size of the limbs that are been viewed but also on how much control subjects feel they have of the movements in their hands-specifically the relationship to the right hand condition (4) seems to have an analgesic effect for cold pain and heat pain.

Background and aims/objectives Offset analgesia (OA) is a newly discovered pain-inhibiting mechanism, defined as a disproportionately large decrease in pain perception in response to a decrease in noxious stimulus intensity. Offset analgesia is usually evoked using heat as noxious stimulus (44–47 °C) and a slight decrease (1 °C) in stimulus intensity causes the volunteers to be pain-free for 5–10 s, despite the presence of a constant noxious stimulus. The aim of the present study was to evaluate whether the OA phenomenon is reproducible within the same day and between different days in order to evaluate whether the phenomenon can be used as a prognostic/diagnostic tool or as a potential therapeutic target in pain treatment. Methods Eighteen healthy volunteers were presented to painful thermal stimuli on the volar forearm, in three contiguous phases (first phase: 46 °C applied for 5 s; second phase: 47 °C applied for 5 s; third phase: 46 °C applied for 20 s). Continuous sensory ratings obtained with a handheld sliding VAS-scale and continuous 64-channel electroencephalographic (EEG) recordings were obtained throughout the three phases. Volunteers participated on two different days separated by a minimum of 7 days. Results Reproducibility was examined for numerous parameters (e.g. peak pain intensity, magnitude of pain-relief, AUC) related to the continuous pain ratings. Two-way ANOVA, ICC, and CV displayed a high degree of reproducibility both within the same day as well as between different days ( P -values >0.05 and ICC values >0.6). EEG recordings were decomposed by spectral analysis, to obtain the normalized power in the delta, theta, alpha, beta and gamma frequency bands. Conclusion The present model displayed high reproducibility, making it suitable for further studies using OA. This may provide a unique approach to study basic pain and pharmacological intervention in healthy volunteers as well as in patients with dysfunctional pain inhibition. Continuous EEG recordings enable objective evaluation of dynamic changes in brainwave activity during OA, and can possibly be used as an objective biomarker to assess the underlying mechanisms of OA.

Background/aims An objective correlate of ongoing painful process in peripheral tissue would represent a progress in the analysis of pain. The aim of this study was to investigate if the extent of the injury and inflammation in musculoskeletal injuries can be visualized, quantified and followed over time using positron emission tomography (PET) with the radioligand [ 11 C]-D-deprenyl. Methods Eight otherwise healthy patients with unilateral ankle sprain were PET-imaged acutely and followed up twice, first a month and then up to over one year after injury. Results Acutely [ 11 C]-D-deprenyl uptake was significantly increased by a factor 10.7 (range 2.9–37.3) in the injury sites as compared to the intact ankle. During healing [ 11 C]-D-deprenyl uptake was reduced, but not normalized until after 11 months. Conclusions Patients experiencing persistent pain showed prolonged [ 11 C]-D-deprenyl uptake in the injury sites. Thus, PET can be used to visualize, quantify and follow painful processes in peripheral tissue.

Background/aims Mirror-image sensory dysfunction (MISD) has been described in various medical conditions, but has not been systematically characterized following major surgery. Methods The presence of MISD was evaluated with standardized thermal and mechanical stimuli, in a group of preoperative patients scheduled for thoracotomy ( n = 14) and in patients with post-thoracotomy pain syndrome (PTPS = 14). The primary outcome was areas with sensory dysfunction evaluated by dynamic sensory mapping with metal-rollers and a brush. The test procedures were repeated after 2 weeks in PTPS-patients. Results The preoperative patients all had normal sensory mapping. In all PTPS-patients sensory dysfunction on the surgical side was observed, while in 12/14 patients MISD was demonstrated. In 5/12 patients, the spatial distribution of MISD areas corresponded to the sensory dysfunction on the surgical side. The total areas of sensory dysfunction (median, [25–75% interquartile range]) were Day 1, on the surgical side 500 cm 2 (289–636) and on the non-surgical side 60cm 2 (0–379 [ P <0.005]), and on Day 2, 355cm 2 (266–697) and 81 cm 2 (0–202379 [ P < 0.0002]), respectively. Area of sensory dysfunction on the surgical side, respectively on the non- surgical side, did not differ significantly between Day 1 and Day 2 ( P >0.5). Conclusions Mirror-image sensory dysfunction is a prevalent finding in PTPS-patients. The sensory dysfunction does not seem related to the underlying lung neoplasm per se. The study demonstrated a high day-to-day variability both in sensory dysfunction areas in the surgical side and in MISD-areas. The pathophysiological mechanisms behind MISD in chronic post-surgery pain deserve further study.

Background/aims Pain is a common problem which significantly impacts on quality of life. Clinical pain is complicated to study due to numerous confounding variables. Normal volunteer models use standardised painful stimuli with resulting reduced phenotype variability. Current studies suggest an association between genetic variability and pain sensitivity. Methods Data from 50 healthy volunteers in three studies of multi-modal, multi-tissue experimental pain stimulation were included. Skin heat, muscle cuff pressure and visceral pressure were analysed. Genetic variants in the genes coding for the mu, delta and kappa opioid receptors (OPRM, OPRD and OPRK) were studied using multivariate regression modelling to investigate association with pain sensitivity. Results Reproducibility of baseline data for skin heat, muscle cuff pressure and visceral pressure between studies was confirmed (Cronbach’s α > 0.8). Gender differences in pain sensitivity were seen. Females were more sensitive to skin heat and muscle pressure ( P =0.006 and 0.02 respectively). Genetic associations were also found. OPRK was associated with both skin heat pain ( P =0.009) and muscle cuff pain ( P =0.003). Visceral pressure pain was not associated with either gender or genotype. Conclusion Genetic variations in the kappa opioid receptor appear to mediate different pain modalities. Gender remains an independent predictor of pain sensitivity.

Background/aims Data on mechanical sensitivity and cutaneous allodynia in different types and phases of migraine headaches are limited. Existence and pattern of such symptoms may advance the understanding of neurophysiological mechanisms, assist clinical evaluation of the patients, and further improve management. Hence, in a large controlled study on migraine patients, mechanical sensitivity and cutaneous allodynia were assessed together with clinical markers. Methods Sensitivity to mechanical stimuli was measured in migraine patients during attack (within 2 h of headache onset), within remission phase (48–72 h after headache onset), and in pain-free periods (>5 days pain-free) in comparison with sex-and age-matched healthy controls. Pin-prick stimulation was performed in the temple region in the pain-referred side using weight-calibrated pins (8, 16, 32, 64, 128, 256 mN) in a randomized order (3 stimuli lasting 2 s), with the patient rating the sensation on a 10-point numerical scale. Pressure Pain Threshold (PPT) was assessed using a handheld algometer (1 cm 2 rubber probe) over the anterior aspect of the temporal muscle (30 kPa/s, 3 times). Results Preliminary analysis revealed increased mechanical sensitivity to Pin-prick during all phases in migraine patients ( n = 4) compared to healthy controls ( n = 5), and likewise increased during attack and remission phases compared to pain-free periods within patients. PPT, assessing mainly muscle nociception, showed a tendency to decline during attack and remission phases (89 ± 13% and 82 ± 6%, respectively) compared to pain-free periods, with even higher sensitivity during attack and remission phases (80 ± 12% and 75 ± 11.1%, respectively) compared to healthy controls. Conclusions The current preliminary observed tendencies imply the presence of mechanical hypersensitivity in migraine patients with a notable change during attack and remission phases. This study is ongoing and no firm conclusion can be stated. In addition, alteration of mechanical sensitivity in different phases will be correlated to objective assessments of biological markers in serum specimens of the study population.

Background/aims Electroencephalography (EEG) recorded as evoked brain potentials (EPs) reflects the cortical processing to an external event. This approach is often used to study the altered response to acute pain in chronic pain patients compared to healthy volunteers. However, discrimination of the responses from the study populations is a non-trivial task, which calls for improved objective methods. Methods To develop and validate a new methodology, we analyzed data from 16 type-1 diabetes mellitus patients and 15 age and gender matched volunteers, by means of brain activity recorded from 62 EEG channels. The EEG signals were recorded as EPs elicited by painful electrical stimulations in the oesophagus with an intensity corresponding to the individual pain detection threshold. The EPs from all channels and subjects were decomposed simultaneously by a temporal matching pursuit (TMP) algorithm with Gabor atoms. Results Amplitude and phase features were classified by a support vector machine (SVM) to discriminate patients from healthy volunteers. A classification performance of 93.1% ( P <0.001) was obtained when applying a majority voting scheme to the 3 best performing channels (FC4, C1, and C6) and including features from 2 atoms. The most discriminative features were determined by the slope coefficients from the SVM decision rule, which identified the biomarkers as delayed latency of the first atom (N2–P2 complex) and decreased amplitude of the second atom (NI–P1 complex). Conclusion The combination of TMP and SVM is a novel approach to classify two study populations, which may provide a new objective tool to identify biomarkers from various chronic pain populations.

Background/aims Pain following stroke is common and affects the quality of life in stroke survivors. The most common types of pain following stroke are headache, shoulder pain, other joint pain and central post-stroke pain (CPSP). The objectives of this study were to determine the prevalence of pain at stroke onset and 6 months after stroke and classify the different pain types. Methods All consecutively eligible patients admitted to the Stroke Unit at Aarhus University Hospital from February 1 to October 1, 2007 and from February 1 to August 1, 2008 were included. An interview on pain prior to and at stroke onset was conducted at admission followed by interviews on current pain by phone 3 and 6 months after the stroke. Results A total of 300 patients were included in the study, and 275 of them completed the 6-month follow-up. The mean age of the 275 patients was 65.9 years old and 55.2% was male. Pain prior to stroke was reported by 49.1% of patients at stroke onset and newly developed pain defined as pain not experienced prior to stroke was reported by 37.8% at stroke onset, 41.8% at the 3-month follow-up and 45.8% at the six month follow-up. The impact on daily life was moderate to severe in 36.4% and 33.6% of the patients with newly developed pain at the 3- and 6-month follow-up, respectively. More than one type of newly developed pain was experienced by 32.2% and 36.5% at the 3- and 6-month follow-up. Headache was reported by 33.5% at stroke onset and newly developed headache by 15.3% at 3-month follow-up and 13.1% at 6-month follow-up. Shoulder pain was reported by 1.5%, 13.1% and 16.4% at stroke onset, and the 3-and 6-month follow-up, respectively. Other joint pain was reported by 7.4% at 3-month and 11.7% at 6-month follow-up. Evoked pain was experienced by 3.6% at stroke onset and by 5.5% and 9.1% at the follow-up interviews. Other types of pain were also reported; 7.3% at stroke onset, 18.9% at 3-month follow-up and 20.0% at 6-month follow-up. Possible CPSP was identified in 10.5% of patients from the different pain groups. Conclusion Pain following stroke is common and may have a considerable effect on the everyday life of the patient.

Background Chronic pain after surgical procedures in children has gained limited attention. Chronic thoracic pain after cardiac surgery is common, and has a significant impact on daily life in adults. The study aim was to investigate the prevalence and etiology of chronic pain after cardiac surgery via sternotomy in children. Methods The study included a prospective clinical examination with quantitative sensory testing 3 months after surgery, and a retrospective survey of children, who underwent cardiac surgery 10-60 months earlier. Children were to be at least 4 years old at the time of completing the questionnaire. They were asked to recall the intensity of the post-operative pain. The questionnaire assessed pain descriptors, situations or activities that could worsen pain, and analgesic consumption. Faces pain scales (0–10) was used to rate the pain intensity. Results Ten children were examined three months after surgery. One child reported ongoing pain. Brush allodynia and pinprick hyperalgesia were present in 4 and 6 children respectively. Hypoesthesia to cold (20 °C) was present in 3 children, and cold allodynia was present in one child in the scar area. The average pressure pain threshold was 71.1 kPa (range 34.3–121 kPa). One hundred and seventy one questionnaires were sent out, and 121 (70.8%) were eligible for analysis. Mean age at the time of surgery was 4.7 years and mean age at questionnaire completion was 8.4. Worst pain intensity in the week after surgery was 5.6 (mean). Any pain “during the recent week” was reported by 26 children, 12 children reported pain intensity ≥4. Two children (1.17%) reported pain intensity ≥4 at the time of questionnaire completion. Pain was evoked by local pressure in 23 (19.0%), and physical activity in 15 (12.4%) children. Itch and pressing were the most frequent pain descriptors chosen by 25 (20.7%) and 20 (16.5%) children, respectively. One child used paracetamol once a week. Conclusions The prevalence of chronic pain following cardiac surgery via median sternotomy in children is low. The pain may have a neuropathic component, but appears to be mild and does not significantly affect daily activities.

Background/aims The mechanisms behind chronic postsurgical pain remains unsettled. Quantitative sensory testing and questioning sensory function may help understand mechanisms behind the transition from acute to chronic pain. The aim of this study was to assess these aspects in postsurgical patients with and without chronic postsurgical pain. Methods 116 women, who answered a questionnaire in a four years follow-up study of pain, sensory changes and quality of life after cosmetic breast augmentation surgery [1], were invited to participate in a psychophysical study. Twenty women answered the request and filled in a questionnaire, and 12 of these women finally met for examination. Results Six of the 12 women had pain in the area of surgery, three were pain-free, but reported sensory changes and three reported no pain or sensory disturbances. We performed a detailed quantitative sensory examination, with a protocol adapted from Rollke et al. [2] While only 3/6 patients in the pain-free group reported hypoesthesia, an area of hypoesthesia to tactile-, heat- and cold stimuli was identified in all subjects when examined (Table 1). Table 1 Number in each group (subjects with pain vs. subjects without pain) showing presence of sensory characteristics. Pain ( N = 6) No pain ( N = 6) Questionnaire Hypoesthesia 5 3 Hyperesthesia 6 3 Examination Hypoesthesia (tactile, heat, cold) 6 6 Hypersensitivity detected 4 1 Hyperpathia to heat 5 5 Paradoxical heat sensation during cold stimulation 4 0 Allodynia, cotton 0 0 Allodynia, brush 0 1 Cold allodynia 5 1 Abnormal temporal summation 5 1 Deep pain after algometry 4 0 The most striking difference between the group reporting pain and the one not reporting pain was the presence of paradoxical heat sensation, cold allodynia, abnormal temporal summation, and the presence of deep pain during/after pressure pain threshold testing with the algometer in the group with pain. Conclusion Self-reported sensory changes under-estimated sensory changes. Sensory testing revealed signs of peripheral nerve injury changes in all subjects, while signs of central nervous changes were found predominantly in patients with persistent pain.

Background In patients with neuropathic pain, Quantitative Sensory Testing (QST) can define different sensory phenotypes thought to be related to different underlying mechanisms. One phenotype with abnormal sensitization of cutaneous nociceptors has been termed irritable nociceptors . Methods This study is a part of a randomized, double-blind, placebo controlled, crossover trial with the anticonvulsant oxcarbazepine. The study is ongoing. In this report, baseline QST measures from patients with peripheral neuropathic pain due to either polyneuropathy (PNP) or peripheral nerve injury (PNI) are analyzed. QST evaluates thresholds for cold and heat detection (CDT, WDT), thermal pain (CPT, HPT), vibration (VDT), pin prick, mechanical detection and pressure pain. Furthermore, wind-up ratio and dynamic mechanical allodynia (DMA) are evaluated. Patients with irritable nociceptors are defined as patient with normal CDT and WDT and either mechanical or thermal allodynia or hyperalgesia. Results By March 2012, 28 patients with PNI and 24 with PNP were included. There was no difference in pain duration (66.2 (53.7) vs. 64.0 (43.3) months, p = 0.87) or pain intensity (NRS, 0 10) (6.6 (1.6) vs. 6.3 (1.7), p = 0.54), but patients with PNI were significantly younger (48.8 (15.1) years) compared to patients with PNP (62.4 (8.5) years), p < 0.001. The percentage of irritable nociceptors in the PNI group was 39.3% and in the PNP group 29.2% ( p = 0.44). The percentage of patients with DMA was 39.3% and 33.3%, respectively ( p = 0.66). Significantly more patients with PNI had thermal allodynia (28.6% vs. 0%, p = 0.005), 6 reported cold allodynia and 4 heat allodynia. Conclusion Preliminary results show that there was no significant difference in percentage of irritable nociceptors between the two groups, but more patients with PNI had thermal allodynia.

Background/aims When studying chronic pain in the general population, other factors besides prevalence may be equally important to establish the scope of the problem. Health related quality of life (HRQoL) is an important indicator for how chronic pain influences and interferes with the individual’s daily life. The relationships between different characteristics in the nature of pain and HRQoL have been investigated, showing number of pain locations and pain severity to be important. However, little is known about the relationship between pattern of chronic pain (constant/intermittent) and impact on HRQoL. The purpose of this study was to investigate the relationships between the pattern of chronic pain and impact on the individual’s HRQoL in a large nationwide population based sample. Methods A postal questionnaire on pain and HRQoL (SF-36), including information letter was sent to a sample of 4500 individuals, aged 20–70 years, randomly drawn from the Icelandic National Registry. Results Of 4500 questionnaires mailed 1586 were returned and completed (35.2%) Majority of respondents were women (56.5%) and the majority were married or cohabitating (73.7%). The total sample mean age was 46.2 years (women 45.3, men 47.3) and respondents were significantly older than non-respondents. The total prevalence of pain ≥3 months was 47.5% with mean duration of 9.3 years (SD = 9.96). One third (31.9%) of participants with pain ≥3 months reported constant pain and 21.4% daily intermittent. The rest reported frequent pain (27.8%) and periodical pain (18.9%). There was a significant relationship between the pattern of pain and both physical and mental components of HRQoL. Participants experiencing constant pain had the lowest scores on both scales. Conclusions The results of this study show that both physical and mental components of HRQoL among individuals experiencing chronic pain are significantly related to the pattern of pain. Constant and daily pain is associated with poorer HRQoL than intermittent or periodical pain.

Background/aims Optimal pain treatment with minimal side-effects is essential for early mobilization and recovery in patients undergoing total knee replacement surgery. Local infiltration analgesia (LIA) with local anaesthetic might be effective and adjuncts such as ketorolac may provide additional effects on opioid requirements and pain. We tested the hypothesis that adding ketorolac significantly improves analgesia after total knee replacement surgery. Methods Sixty patients were enrolled in this prospective double-blinded study and allocated to either group R (placebo) or Group RK (ketorolac 120 mg). All patients received high-volume LIA with 150 ml ropivacaine (300 mg) with epinephrine added either placebo or ketorolac (30 mg) combined with eight 10 ml ropivacaine doses (100 mg) added either placebo or ketorolac (15 mg) administered every 6 h through an intra-articular catheter for 48 h. postoperatively. The primary outcome was patient-controlled morphine consumption from 0–6 and 0–48 h after surgery. Time to first rescue administration, pain intensity (0–100 mm visual analogue scale) at rest and during mobilization and side-effects were recorded until 96 h after surgery. Results Six and forty-eight morphine consumption was significantly reduced in group RK compared with group R. Time to first rescue analgesia was significantly prolonged with 4 h in group RK [median (IQR)] 490 min (248–617) compared with 223 min (115–319) group R ( P < 0.02). Pain at rest and during movement was significantly reduced for 48 h with the addition of ketorolac. Length of hospital stay was reduced with one day in group RK [median (IQR)] 2 days (2–3) compared with group R3 days (2–3) ( P =0.004). Conclusions Ketorolac resulted in a 75% reduction in 48 h postoperative morphine requirements. This was also significantly associated with prolonged analgesia, reduced pain intensity scores at rest and during movement and reduced length of hospital stay.

Background Neuropathic pain is usually treated with antidepressants and anticonvulsant. The use of systemic treatment is, however, limited due to poor tolerability and low efficacy. Qutenza, a topical capsaicin patch (8%), is a relatively new treatment for patients with peripheral neuropathic pain (PNP) conditions. The indication for using topical capsaicin treatment is peripheral neuropathic pain in patients without diabetes. Aim To describe the use of topical capsaicin treatment in a pain clinic in patients with PNP. Methods Case series of patients in a neuropathic pain clinic. Results Since October 2010, 40 patients with PNP with different aetiologies have been treated with topical capsaicin; 14 patients had nerve injuries in feet or lower leg or polyneuropathy, 13 patients had nerve lesions related to fingers, hands or arms, seven patients had pain after thoracotomy, four patients postherpetic neuralgia, and two patients had other lesions. Almost half of the patients (47%) were responders and achieved a decrease in pain intensity as well as increased their quality of life (QoL). Responders received 1–6 treatments with capsaicin. Most responders were found in the post-thoracotomy group, of which 86% had a clinical significant reduction in pain. In the group with injuries to the hands, fingers and arms, 46% experienced a reduction in pain. Only 23% of patients with PNP in the feet and lower leg were responders; these patients had a clinical significant increase in QoL. Conclusion In 40 patients with PNP who were treated with topical capsaicin, we found an increase in QoL and a decrease in mean pain intensity of 3 measured on a VAS scale (0–10) in 47% of the treated patients.

Background/aims The presence and severity of concussion related symptoms after acute whiplash injury are debatable. In this study we examine the distribution and development of the burden of concussion related symptoms in whiplash patients. Methods Consecutively 141 acute whiplash patients and 40 ankle injured controls were recruited from emergency units and were examined after 1 week, 1, 3, 6, 12 months obtaining neck/head VAS score, number-of-non-painful complaints, epidemiological, social, psychological data and neurological examination, active neck mobility, and furthermore muscle tenderness and pain response, strength and duration of neck muscles. Risk factors derived (reduced CROM, intense neckpain/headache, multiple non-pain complaints) were applied in a Risk Assessment Score and divided into 7 risk-strata (refer Kasch et al., Spine 2011). After 1 week and 6 months whiplash patients fulfilled the Rivermead Oxford Head Injury questionnaire (10 items, score from 0 = no change to 4 = very marked change, Danish Version, total score range from 0 to 40). Results 138 acute whiplash patients fulfilled the Rivermead Oxford Head Injury questionnaire after 1 week and 111 after 6 months. The distribution was markedly different in the risk strata, in stratum 7 the sum score was a factor 10 higher than stratum 1 after 1 week (Kruskal-Wallis, p < 1.4 × 10 –7 ) and remained high 6 months after injury ( p < 0.05). Conclusion Mild concussion symptoms do not necessarily reflect eventual concussion, but are found after injuries with no direct head trauma and amnesia e.g. whiplash injuries. The Risk Assessment Score fits nicely with the burden of concussion related symptoms after whiplash injury.

Background/aims HIV/AIDS is a disease that is taking many lives in Ghana and other countries in Africa. It is a disease that has infected people in Sweden, though not as many as Africa has reported. The present investigation concerns how HIV/AIDS patients in Ghana, a cultural tropic climate, and patients in Sweden, the Nordic region, experience their pain. Methods With empirical data from both countries, the research will unveil how these patients cope or adapt to their illness with all the attention they receive from the environments and their native resources. Apart from the theoretical considerations where literature/secondary sources on the subject will be analysed, the investigation will administer Coping Experience Questionnaires (CEQ) and The Medical Outcomes Study Short Form 36 (SF36) to reach a deeper analysis on how they adapt to their illness and wellbeing. The study will also utilise both the Structured Interviewed (SI) and In-depth Interview (IDI) to muster relevant data about their experience with hospital environments, native resources, and human relations. Results and conclusion It is estimated that the results of the investigation will firstly, help doctoral students to comprehend coping strategies and differences in conditions with HIV/AID patients in diverse cultures, and secondly, help to understand psychiatry care of patients from different cultural climates.

Background Previously, central sensitization has been found in chronic, primary headaches but pain perception in MOH patients has only scarcely been studied. Aim To investigate pain perception before and during detoxification in patients with medication overuse headache (MOH). Methods 35 patients with MOH following structured detoxification programmes were tested before and 2, 6 and 12 months after withdrawal and 40 age and sex matched, healthy volunteers were tested for comparison. We measured cephalic and extra cephalic pressure pain thresholds (PPT) and supra-threshold pressure pain (STPP) as well as extra cephalic pain thresholds, supra-threshold pain and wind-up for electrical stimulation. Results At baseline, cephalic and extra cephalic PPTs were significantly lower in patients with MOH compared with healthy volunteers. Cephalic STPP was significantly higher in MOH patients compared with healthy volunteers but decreased significantly from baseline to the 6-month and 12-month follow-up. Supra-threshold pain for a single electrical stimulus was significantly higher in MOH patients compared with healthy volunteers. In contrast to healthy volunteers, patients with MOH did not exhibit wind-up before withdrawal. After 2 months, MOH patients had regained ability to wind-up and this persisted at 6-month and 12-month follow-up. Conclusions Patients with MOH have altered pain sensation and exhibit both allodynia and hyperalgesia indicating central sensitization. Withdrawal from medication overuse causes significant decrease in central sensitization. The ability to wind-up is altered in MOH patients, probably as a consequence of medication overuse, but it can be regained after withdrawal. These findings emphasize the need for detoxification in MOH.

Aim To evaluate the long-term efficacy of two different treatment programmes for medication-overuse headache (MOH) in so-called treatment-resistant patients. Methods MOH patients, who had previously been unsuccessfully treated by neurologists, were enrolled in one of 2 structured detoxification programmes in a tertiary headache centre: (A) a one-week withdrawal with restricted analgesics, rescue medications and prophylactics from Day 1 followed by advice of restricted intake of symptomatic medications or (B) a 2-month drug-free period and multidisciplinary education in groups and subsequent initiation of restricted symptomatic medication and prophylactics as required. All patients were closely followed up for a year. Results 86 of 98 patients completed the 12-month follow-up. Totally, headache frequency was reduced by 39% ( p <0.001), medication use by 63% ( p <0.001) and 83% remained cured of MOH. Headache frequency was reduced with more than 50% in 42 patients (49%) and 52 (61%) reverted to episodic headache, and with no difference between the groups. Patients in programme B used significantly less symptomatic medication: 6.5 days/4 weeks compared with 8.7 days/4 weeks in programme A ( p = 0.02), and the 56% of patients in programme B who needed prophylactic medication was significantly less than the 80% in programme A ( p = 0.02). Further, programme B required fewer resources from the staff. Conclusion Structured detoxification with close follow-up by a multidisciplinary team for one year is highly effective in patients with previously treatment-resistant MOH. We recommend a multidisciplinary educational programme for patients in groups due to cost-effectiveness and limited use of medication.