Volume 5, Issue 3

Background and aims Exposure in vivo for patients with fear-related chronic pain has a strong theoretical base as well as empirical support. However, the treatment does not work for every patient and overall the effect size is only moderate, underscoring the need for improved treatments. One possible way forward might be to integrate an emotion regulation approach since emotions are potent during exposure and because distressing emotions may both interfere with exposure procedures and patient motivation to engage in exposure. To this end, we proposed to incorporate an emotion-regulation focus into the standard exposure in vivo procedure, and delivered in the framework of achieving relevant personal goals. The aim of this study then was to test the feasibility of the method as well as to describe its effects. Method We tested a hybrid treatment combining an emotion-regulation approach informed by Dialectical Behaviour Therapy (DBT) with a traditional exposure protocol in a controlled, single-subject design where each of the six participants served as its own control. In this design participants first make ratings to establish a baseline from which results during treatment and the five month follow-up may then be compared. To achieve comparisons, participants completed diary booklets containing a variety of standardized measures including pain catastrophizing, pain intensity, acceptance, and function. Results Compared to baseline, all subjects improved on key variables, including catastrophizing, acceptance, and negative affect, at both post treatment and follow up. For 5 of the 6 subjects considerable gains were also made for pain intensity and physical function. Criteria were established for each measure to help determine whether the improvements were clinically significant. Five of the six participants had consistent results showing clinically significant improvements across all the measures. The sixth participant had mixed results demonstrating improvements on several variables, but not on pain intensity or function. Conclusions This emotion-regulation hybrid exposure intervention resulted in considerable improvements for the participants. The results of this study underscore the potential utility of addressing emotions in the treatment of chronic pain. Further, they support the idea that targeting emotional stimuli and using emotion regulation skills in conjunction with usual exposure may be important for obtaining the best results. Finally, we found that this treatment is feasible to provide and may be an important addition to usual exposure. However, since we did not directly compare this hybrid treatment with other treatments, additional research is needed before firm conclusions can be made. Implications Addressing emotional distress in the treatment of patients suffering chronic pain appears to be quite relevant. Emotion regulation skills, employed together with exposure in vivo, hold the promise of being useful tools for achieving better results for patients suffering fear-related and emotionally distressing chronic pain.

Background and aims Affect balance reflects relative levels of negative affect (NA) and positive affect (PA) and includes four styles: Healthy (low NA/high PA), Depressive (high NA/low PA), Reactive (high NA/high PA) and Low (low NA/low PA). These affect balance styles may have important associations with clinical outcomes in patients with fibromyalgia. Herein, we evaluated the severity of core fibromyalgia symptom domains as described by the Outcomes Research in Rheumatology-Fibromyalgia working group in the context of the four affect balance styles. Methods Data from 735 patients with fibromyalgia who completed the Brief Pain Inventory, Multidimensional Fatigue Inventory, Profile of Mood States, Medical Outcomes Sleep Scale, Multiple Ability Self-Report Questionnaire, Fibromyalgia Impact Questionnaire-Revised, Medical Outcomes Study Short Form-36, and Positive and Negative Affect Schedule were included in this analysis. Results The majority (51.8%) of patients in our sample had a Depressive affect balance style; compared to patients with a Healthy affect balance style, they scored significantly worse in all fibromyalgia symptom domains including pain, fatigue, sleep disturbance, dyscognition, depression, anxiety, stiffness, and functional status ( P = <.001 to .004). Overall, patients with a Healthy affect balance style had the lowest level of symptoms, while symptom levels of those with Reactive and Low affect balance styles were distributed in between those of the Depressive and Healthy groups. Conclusions and implications The results of our cross-sectional study suggest that having a Healthy affect balance style is associated with better physical and psychological symptom profiles in fibromyalgia. Futures studies evaluating these associations longitudinally could provide rationale for evaluating the effect of psychological interventions on affect balance and clinical outcomes in fibromyalgia.

Background Post dural puncture headache (PDPH) is an iatrogenic cause of patient morbidity in pain management after spinal or epidural anaesthesia, as well as after diagnostic lumbar puncture. Most patients respond to conservative treatment or to epidural blood patch, yet limited options for effective treatment are available for patients who fail these treatments or present with theoretical contraindication. Case report We present a case of a patient with previously diagnosed human immunodeficiency virus and hepatitis C, who presented with signs of PDPH, which placed him at a theoretical risk of meningeal seeding of the virus during the blood patching procedure. Conclusion We successfully treated the post dural puncture headache and avoided the risk of viral seeding of the meninges by using a fibrin sealant.

Background Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain refractory to conventional treatment. SCS treatment consists of one or more leads implanted in the epidural space of the spinal canal, connected to an implantable pulse generator (IPG). Each lead carries a number of contacts capable of delivering a weak electrical current to the spinal cord, evoking a feeling of peripheral paresthesia. With correct indication and if implanted by an experienced implanter, success rates generally are in the range of about 50–75%. Common indications include complex regional pain syndrome (CRPS I), angina pectoris, and radicular pain after failed back surgery syndrome, and the treatment is also used to treat stump pain after amputation, and pain due to peripheral nerve injury, peripheral vascular disease, and diabetic neuropathy. Recommended contraindications for the treatment include pregnancy, coagulopathy, severe addiction to psychoactive substances, and lack of ability to cooperate (e.g. due to active psychosis or cognitive impairment). Most common complications to the treatment include lead migration, lead breakage, infection, pain over the implant, and dural puncture. Despite extensive research in the area, the mechanisms of action are still only partially understood. Methods In this topical review the historical background behind the treatment is described and the current theories on the mechanism of action are presented. The implantation procedure is described in detail and illustrated with a series of intraoperative pictures. Finally, indications for SCS are discussed along with some of the controversies surrounding the therapy. Implications The reader is presented with a broad overview of spinal cord stimulation, including the historical and theoretical background, practical implantation technique, and clinical application.

Background and aims The prevalence of depression is increased among patients with abdominal pain (AP) and Irritable Bowel Syndrome (IBS), but little is known about this association among adolescents in the general population. Furthermore, there is considerable uncertainty about exactly which dimensions of AP and IBS are associated with depression. The aims of this study were therefore: (a) to describe the prevalence of AP, IBS and depression in a representative sample of adolescents, (b) to analyze the association of AP and IBS with depression and lastly, (c) to analyze the relationship between depression and specific AP and IBS symptom dimensions, i.e. pain intensity, frequency, duration, and distribution, the presence of co-morbid non-abdominal pain, and the specific bowel systems distinguishing IBS from AP in general. Materials and methods Self-reported symptoms of AP (monthly or more frequent), IBS (Rome III 2006 criteria), co-morbid chronic pain and depression (The Short Mood and Feeling Questionnaire sum-score ≥11) were recorded among 961 adolescents (mean age 16.1 y and 48.8% girls), participating in a population based study in 2010–2011. Multiple logistic regression carried out to analyze the association of AP and IBS with depression, adjusting for sex, parental level of education (<college or ≥college) and co-morbid chronic pain. Among the AP cases, the association of different AP dimensions and of the specific bowel symptoms in IBS with depression were analyzed in a stepwise multiple logistic regression model. Results Monthly or more frequent AP was reported by 27% of the participants ( n = 259) and 8.2% ( n = 77) met the Rome III IBS criteria. The prevalence of depression was 11.5% (girls 15.9% and boys 7.3%). The prevalence of depression was higher among both AP and IBS cases compared to in controls (20.5%, 24.7% and 8.1% respectively), but there was no evidence that depression rates differed between the two case groups (IBS: OR = 2.5, 95% CI = 1.6–3.9; AP: OR = 2.4 with 95% CI = 1.3–4.4, after adjusting for sex, parental level of education and co-morbid chronic pain). In the regression analyses within the AP group, the following symptom dimensions were independently associated with depression: severe abdominal pain intensity (OR = 4.0; CI = 1.5–10.7), widespread abdominal pain (OR = 5.5; CI = 2.6–11.8) and presence of co-morbid chronic pain (OR = 3.3; CI = 1.6–6.8). Sex, parental education, and other abdominal pain symptom dimensions, including bowel symptoms that distinguish IBS from AP, were not independently associated with depression. Conclusions and implications The prevalence of depression is considerably increased among adolescents with AP and IBS in the general population, in particular among those reporting severe, widespread abdominal pain, and co-morbid chronic pain. Evaluating these symptom dimensions may be of value for identifying subgroups adolescents with AP and IBS that have greater risk of depression.

Objectives One in five women under the age of 30 report recurrent genital pain and pain during sexual intercourse. Female genital pain negatively affects sexual and general health, as well as dyadic function and quality of life. Although the current field of research and clinical expertise in general agree upon a biopsychosocial conceptualization, there is still a lack of theoretical models describing the psychosocial mechanisms involved in the development of genital pain. Originally developed to outline the transition from acute to chronic back pain, the fear avoidance (FA) model has lately been proposed as a possible tool in illustrating the mechanisms involved in genital pain. However, only few studies have empirically tested the components of the FA model empirically. The aim of the present study is to examine fear avoidance beliefs, pain catastrophizing, and symptoms of depression and anxiety among women reporting genital pain, and to relate these concepts to sexual satisfaction/function and the characteristics of pain. Methods The study was a population-based study using a postal questionnaire administered to 4052 women (age 18–35). Of these 944 (response rate: 23%) took part in the study. Results Genital pain of six months duration was reported by 16.1% of the women. Women with pain reported elevated levels of symptoms of anxiety, fear avoidance beliefs, pain catastrophizing and anxiety sensitivity. Symptoms of anxiety also predicted pain in the explanatory model together with vaginal tension and fungal infection. Vaginal tension has previously been described as a fear-response to painful intercourse and the results thereby seem to give further support to viewing genital pain from a fear avoidance perspective. Furthermore, fear avoidance beliefs seem to be of similar importance as lack of desire for the experience of sexual satisfaction and could also predict pain during specific activities among women with pain. The results also indicate that sexual satisfaction is related to a specific pain-related fear, rather than a heightened level of general anxiety. Conclusions The study had a low response rate, but still indicates that genital pain is common and is associated with several aspects of fear and avoidance. In sum, the results support the FA model by giving strong support for fear reactions (vaginal tension) and fear avoidance beliefs, and moderate support for negative affect. In the model negative affect drives pain catastrophizing. Implications It seems that the experience of genital pain among women in the general population is common and could be associated with increased levels of anxiety and fear-avoidance beliefs. However, the associations should not be understood in isolation from physiological mechanisms but seem to indicate interactions between, e.g. fungal infections, negative appraisals of pain and symptoms, lack of sexual function and satisfaction and increased pain experience. It is possible that psychological mechanisms work in the transition from acute physiological pain to chronic psychologically maintained pain in terms of secondary reactions to, e.g. repeated fungal infections by adding emotional distress, fear of pain and avoidance behaviours.

Background and aims The problem of sexual pain is an area that has been shamefully ignored by both the pain community and the health service authorities. Although about 40% of women report such pain and 30% report it during their last intercourse, sexual pain has historically not even been considered a pain problem. The objectives of the present study was to present a background to the problem of female sexual pain, further elaborate on the problem and offer some direction for how advances might be concretely made. Discussion Genital pain is common and many women describe pain during several non-sexual activities. Therefore describing the pain strictly as a sexual problem, threatens to lose important information about the experience of pain which will be misleading both in assessment and treatment. Instead, seeing the problem as a multidimensional pain condition with debilitating sexual consequences is suggested. It has become apparent that although biological aspects are central in the experience of genital pain, psychological and social aspects may play a major role. The fear avoidance model which has played a major role in our understanding of the development of chronic musculoskeletal pain, also seems to be applicable in genital pain conditions. However, one has to be aware of certain differences when comparing genital pain from musculoskeletal conditions. In addition, there is a lack of established guidelines for assessing or treating unexplained genital pain conditions, and there is a risk of not acknowledging the role of socio-cultural context on how female sexuality is viewed. The problem of recurrent sexual pain is a highly volatile, personal, and socially weighted experience. Because of the lack of understanding of the mechanisms, it is a risk of over-emphasizing the role of vaginal penetration in the assessment and treatment of female sexual pain and clinicians may simply fail to investigate sexual function from a broader perspective. Conclusions and implications There is a growing interest in the problem of female genital pain and associated problems with sexual pain. However, research predominately refers to the field of sex research, and the involvement from the pain community has to date been relatively low. There is an immediate need to identify the psychosocial mechanisms involved in the transition from acute to chronic genital pain in women and to address these components in treatment using established methods. Since sexual pain is far more than pain during vaginal penetration, there is a risk of treatment interventions being oriented towards performance in terms of a narrowly defined sexual behavior instead of focusing on valued activities, meaning and pleasure for the individual. Assessment and treatment have to include a broad perspective on pain and on sex.

Background and aims The investigation was conducted among six practitioners and twenty-two patients in rural Ghana, where both practitioners and patients, were asked to unveil effective methods of treating pain and pain disabilities. Methods The investigation utilised strictly observational methods in acquiring data from two communities. Both patients and practitioners were later interviewed in a manner that elicited certain information needed to provide accurate understanding concerning these treatments methods they give to patients. These participant observations yielded important data, which enlightened us on appropriate techniques that serve the need and expectations of rural dwellers in their management and coping with pain disabilities. Results Careful treatment methods include the use of various herbal medicinal plants in order to supplement the official drugs administered by doctors. Those methods consist of incisions, oral, nasal drops, anal insertions, bandaging with use of strong pepper and ginger, and rubbing of medicines in a lotion form on the pain affected skin or areas. Treatments serve as “first aid” where pain disabilities are treated to many troubled patients with anxiety, confusion, and shock. Doctors in highly equipped hospitals are aware of these pain treatments in the less populated regions, but they are at variance as to whether patients receive maximum help. Conclusion In regard to pain treatments, earlier treatments received from centres where non-scientific practitioners operate, do not reveal harm done to patients; they do provide support and serve as “First aid” upon which biomedical practitioners perform their own specialist treatments.

Introduction Offset analgesia (OA) is a temporal perceptual mechanism in which subjective pain ratings decrease disproportionally when a noxious heat stimulus is decreased by 1–3 ◦ C. Whether OA is a peripheral, spinal or supraspinal mechanism remains unknown. The stimulation of afferent nociceptors in the foot, leads to a spinal nociceptive withdrawal reflex (NWR) which is mediated through the wide dynamic range (WDR) neurons and therefore under descending control. We hypothesized that OA affects the spinal nociceptive neurons resulting in an attenuation of the NWR during OA. Methods Four heat stimulations profiles were applied to the lower legs divided into four segments of 5 s, 5 s, 5 s, and 15 s, respectively: Offset Analgesia Trial (OAT) (48, 49, 48, 48 ◦ C), Offset Baseline Trial (OBT) (48, 49, 32, 32 ◦ C), Constant Heat Trial (CHT) (4 × 48 ◦ C), and Baseline Trial (BT) (4 × 32 ◦ C). Subjects rated the pain intensity continuously using a visual analog scale (VAS). NWR were evoked by electrical stimulation of the plantar foot and assessed once during each segment by recording EMG from the tibialis anterior muscle. Results VAS-ratings were lower during the third period of OAT compared to CHT ( p < 0.001). However, there was no difference ( p > 0.05) comparing the NWR size between OAT, OBT, CHT, and BT throughout the time periods. Conclusions The NWR was not affected by OA suggesting that spinal WDR plays a limited role in the OA mechanism. Whether peripheral- or supraspinal mechanisms are responsible the OA phenomenon remains unknown.

Aims Axonal hyperexcitability in peripheral nerves has been observed in patients with neuropathic pain [1]. The use-dependent propagation of double pulses, recovery cycles, was found to be different in patients relative to healthy controls. Methods We study the mechanisms underlying the recovery cycle phenomenon using a biophysical model of a C-fiber [2]. The model represents the spatial extent of the axon including its passive properties as well as ion channels of Hodgkin-Huxley type. In vitro voltage clamp recordings from dissociated small DRG somata from rat were performed to assess model predictions. Results The model was able to replicate the transitions in excitability from subnormal to supernormal observed experimentally. For the model, supernormality depended on the degree of conduction slowing which in turn depends upon the frequency of stimulation, in accordance with experimental findings. In particular, we show that activity dependent conduction slowing is produced by the accumulation of intraaxonal sodium. We further show that the supernormal phase results from a reduced potassium current K dr as a result of accumulation of periaxonal potassium in concert with a reduced influx of sodium through Nav1.7 relative to Nav1.8 current. This theoretical prediction of a relative shift in the sodium currents was supported by data from an in vitro preparation of small rat DRG somata showing a relative reduction in the magnitude of TTX-sensitive to TTX-resistant whole cell currents. Conclusions By providing mechanistic explanations of axonal excitability in terms of changes in ion channel activity, we suggest these channel changes can subsequently be used to discuss mechanisms of neuropathic pain.

Aims The present study investigated expression and overall function of transient receptor potential vanilloid-1 (TRPV1) on trigeminal ganglion (TG) neurons and satellite glial cells (SGCs) in a whole-organ culture model to provide further information on association of TG with craniofacial nociception. Methods For TRPV1 receptor expression on neurons and SGCs, immunohistochemistry was performed on 24 cultured trigeminal ganglia isolated from male adult Sprague–Dawley rats. For the functional assay, the cultured trigeminal ganglia were treated with graded concentrations of capsaicin (0.1 μM, 1 μM, or 10 μM) or vehicle (0.1% ethanol in DMEM) and glutamate release was measured by a competitive enzyme-linked immunosorbent assay (ELISA). Samples were taken at 5, 15, and 30 min. Data from the functional assay were analyzed by two-way repeated measures ANOVA and Tukey post hoc test. Results The preliminary results confirmed the expression of TRPV1 mainly on small (46.6%) and medium (44.2%) sized neurons. In addition, expression of TRPV1 on SGCs was shown. Functionality test of the whole-organ demonstrated a significant increase in glutamate concentration, 30 min after application of 10 μM capsaicin (31.69 ± 6.73 μM) in comparison with vehicle (9.83 ± 2.53 μM) and 0.1 μM capsaicin (11.59 ± 7.04 μM) ( p < 0.01). Conclusions This preliminary study demonstrated the expression of TRPV1 on trigeminal neurons and SGCs in the whole-organ model. Furthermore, capsaicin-evoked glutamate release from the whole-organ culture was detectable under controlled conditions and provided a potential platform for further investigation on TRPV1 stimulation and pharmacological modulation in relation to craniofacial nociception.

Aims Cathepsin S has been reported to be a biomarker of spinal microglial activation, a process suggested to be involved in the pathophysiology of chronic neuropathic pain. So far this has been shown only in animal experiments. The aim of this study was to investigate the concentrations of cathepsin S in human cerebrospinal fluid (CSF) samples from a well-defined patient cohort suffering from neuropathic pain as compared to controls. Methods CSF samples from patients suffering from chronic neuropathic pain ( n = 14) were analyzed for cathepsin S levels using commercial sandwich ELISAs (DY1183, R&D Systems, Minneapolis, MN, USA). Control CSF was sampled from patients undergoing minor urological surgical procedures under spinal anaesthesia ( n = 70), having no obvious pain suffering. Results The neuropathic pain group had significantly higher levels of CSF cathepsin S (median 15189 pg/mL, range 3213–40,040), than the control group (median 5911 pg/mL, range 1909–17,188) ( p < 0.005, Mann–Whitney U -test). Conclusion The results support the existence of microglial activation in chronic neuropathic pain patients. CSF Cathepsin S may serve as a potential biomarker for this specific mechanism linked to neuropathic pain. In the future, Cathepsin S inhibiting drugs might become a new treatment alternative for neurophatic pain.

Aims In inflammation-reactive astrocytes the cell parameters, Ca 2+ signalling, Na + transporters, cytoskeleton, and release of proinflammatory cytokines are affected. We want to re-establish these parameters with agents, which might have a potential to restore the cells back to a normal non-inflammatory level. Methods Astrocytes in primary cultures were incubated with lipopolysaccharide (LPS) (10 ng/ml) for 24 h to become inflammation-reactive. Different parameters were analysed to verify this inflammation: Ca 2+ signalling, Na + /K + -ATPase expression, actin filament organization, and interleukin-1beta release (IL-1β). Results We have used an opioid agonist, endomorphin-1, that stimulates the G i/o protein of the μ-opioid receptor, an opioid antagonist, naloxone, that inhibits the G s protein of the μ-opioid receptor in ultralow concentrations, and an anti-epileptic agent, levetiracetam, that counteracts the release of IL-1β. The combination of these three agents managed to activate the G i/o protein and Na + /K + -ATPase activity, inhibit the G s protein, and decrease the release of IL-1β. The disorganized actin filaments were restored. Conclusions The findings that the important cell parameters in astrocytes were restored back to their normal non-inflammatory state after the cells were treated with the inflammatory agent LPS could be of clinical significance. It may be useful for the treatment of neuroinflammation and also maybe of long-term pain. The astrocyte networks play a significant role and therefore a well-working intercellular Ca 2+ signalling is of utmost importance. Significance These findings put new potential drug regimens towards treatment of neuroinflammation and long-term pain into focus.

Aims Many new potential medicines fail in early clinical development. AZD1386 is a TRPV1 antagonist and was developed for treatment of osteoarthritis pain at AstraZeneca. Following preclinical studies to characterize the compound, translational studies and first time in man studies the challenge is great to select the right doses and study population for the first clinical studies on efficacy in phase II of the drug development process. Methods Different design alternatives in the planning of the dose-finding study for AZD1386 in OA were analysed with regard to statistical considerations, timelines and costs for the different options. Results Based on datasimulations and cost/benefit analysis a 4 week study with adaptive design with interim analysis at 2 weeks for possible dose adjustment or futility stop was chosen. The study was initiated with AZD1386 at to doses 30 and 90 mg and placebo. Based on the fact that the one-sided p -value for the primary analysis (comparison of 90 mg versus placebo) was 0.2891 and larger than 0.2, the data monitoring committee decided that the study was to be stopped after the interim analysis due to lack of efficacy. Conclusions The chosen adaptive design in this Phase IIa/b study enabled an early futility stop. This meant several advantages. Further exposure of patients of a non-efficacious drug could be stopped and resources could be re-allocated earlier as well as monetary savings.

Aims We aimed to find proteins of relevance to the prolonged analgesic effect of spinal cord stimulation (SCS) for patients with neuropathic pain. Methods The proteomes of cerebrospinal fluid (CSF) from 14 neuropathic pain patients using spinal cord stimulation (SCS) was compared to the CSF proteomes of the same patients when not using the stimulator. Samples were analyzed by dimethyl label and label free shotgun proteomics approach. Samples were prepared by immunoaffinity fractionation and then separated by reversed phase nanoliquid chromatography coupled to an electrospray ionization source and analyzed by high resolution tandem mass spectrometry. The proteins were comparatively quantified on the peptide level and ranked based on numbers of regulated peptides. Then the dimethyl and label free analysis results were combined. In order to group proteins by function and interactions, a functional enrichment network analysis was performed using the String (Search Tool for the Retrieval of Interacting Genes/Proteins) database on all significantly differentially expressed proteins. Results We found 87 differentially expressed proteins. Network analysis showed a high level of enrichment in interactions between the proteins involved in platelet degranulation and wound healing with p -values 2.48E−11 and 4.58E−08. We also recognized two additional clusters related to complement and coagulation cascades and neuropeptides. None of these proteins have been implicated in SCS mechanism previously. Conclusions Up- and down-regulations of immunological proteins and neuropeptides may explain the prolonged relief of neuropathic pain obtained after SCS. These findings contribute a new basis for understanding of SCS analgesic mechanism in human neuropathic pain. Further verification studies of these initial findings are needed.

Background and aim Treatment responses during placebo periods in randomized clinical trials (RCTs) are quite often substantial and may impede a positive outcome of the trial. It would therefore be beneficial to gain more knowledge on factors contributing to large placebo responses in RCTs. The aim of the current study was to identify predictors of placebo responses in patients with peripheral neuropathic pain. Hypotheses We hypothesized that a high baseline pain intensity and variability will be predictive of large responses during placebo treatment. Furthermore, we hypothesized that expectation for pain relief, few prior treatments and side effects, low scores of pain catastrophizing, anxiety, depression and the personality trait neuroticism and high levels of positive emotions will be predictors of placebo responses. Methods This study is part of a randomized, double-blind, placebo-controlled, crossover study with the anticonvulsant oxcarbazepine. Pain intensity was registered at baseline and during treatment periods on a numerical rating scale (NRS, 0–10) along with expectation for pain relief (NRS), psychological measures (scores for anxiety, depression, catastrophizing, neuroticism, and positive emotions), prior treatments, and side effects. Results Multiple regression analysis with pain reduction during placebo treatment as the dependent variable and baseline pain, age, gender, and pain duration as explanatory variables was highly significant ( R -squared = 0.53, p < 0.001), while other explanatory variables did not reach statistical significance. Further analyses will be carried out. Conclusions Age and gender were not significant predictors of placebo responses in this study. Further results will be presented at the congress. Acknowledgements This study is part of the Innovative Medicines Initiative project EUROPAIN, www.imi.europa.eu.

Aim Among individuals who experience whiplash accidents, around 20% develop chronic pain. We aimed to compare number of painful locations and pain intensity between individuals with chronic whiplash and individuals with other chronic pain, and to investigate whether differences could be explained by pain tolerance. Methods Employing data from the sixth wave of the Tromsø Study, individuals reporting whiplash were compared to individuals with other chronic pain. Number of pain locations was compared using Poisson regression, pain intensity using linear regression. Pain tolerance (cold-pressor test) was compared using cox regression; one model compared individuals with whiplash to those with other chronic pain, another model compared the two groups with chronic pain to pain-free controls. In order to investigate whether pain tolerance could account for differences in pain, the regression models were adjusted for time-till-failure in the cold-pressor test. Results Individuals with whiplash reported a higher number of painful locations (IRR = 5.23, 95%CI: 4.93–5.53 versus IRR = 3.57, 95%CI: 3.50–3.65) and higher pain intensity (mean: 7.80, 95%CI: 7.58–8.02 versus mean: 7.14, 95%CI: 7.08–7.21) than individuals with other chronic pain. Pain tolerance did not differ between these two groups, but compared to pain-free controls individuals in both groups had reduced pain tolerance. Conclusions Individuals with chronic whiplash had reduced pain tolerance compared to individuals without chronic pain, but not compared to individuals with other chronic pain. Reduced pain tolerance can account for some of the increased pain reported by individuals with chronic whiplash compared to controls but not compared to individuals with other chronic pain.

Aims To evaluate the effect of spinal interventions following ISIS guidelines [1]. Methods Data from all patients from April 2012 until February 2014 have been registered and followed up after 4–6 months. Patients were mainly referred from surgeons at the regional hospitals. Employment status, medication, VAS, EQ-5D-5L, EQ-VAS and pain reduction were gathered before and at the follow-up. Only patients receiving any kind of treatment were included. Results So far 419/823 patients have been followed-up. Here we present levels of medication and total pain reduction for all patients and, separately, for patients treated with radio frequency facet joint medial branch neurotomy ( n = 76). Opioids were reduced from 33% to 26% and no use of analgesics increased from 15% to 31% ( p < 0.0159). Opioids in the RF group fell from 31% to 21%, and no use went from 2% to 31%. Of all the patients, 46% had pain reduction >50% and 9% were pain free. In the RF group the figures were 57% and 11%, respectively. No one in the RF group got worse. Conclusion It is important to follow-up your results, even if complete scientific RCT rigour cannot be upheld Our stringent, long-term follow-up can presumably deliver reasonably reliable effect information, a majority of our patients have reduced their medication significantly ( p < 0.001) and more than 50% experience a greater than 50% pain reduction, indicating a significant effect.

Aim This study aims to investigate the proteome of trapezius muscle biopsies of women with chronic widespread pain (CWP) compared to female pain-free controls using proteomic tools. CWP has a high prevalence (10%) resulting in prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Methods Two-dimensional gel electrophoresis (2-DE) analysis and nano-liquid chromatography/mass spectrometry (nLC/MS) was used to study the proteome differences of biopsies from the trapezius muscle between 18 female patients diagnosed with CWP and 19 healthy female controls. Results The proteomic analysis revealed 17 proteins to be statistically significantly expressed between the two groups by which 12 were up-regulated and 5 were down-regulated in the CWP group compared to healthy controls. Many of the proteins were important enzymes in metabolic pathways like the glycolysis and gluconeogenesis (Triosephosphate isomerase, Glyceraldehyde-3-phosphate dehydrogenase, Pyruvate kinase isoenzyme M1/M2 and Fructose-bisphosphate aldolase A, all up-regulated in CWP). Other proteins are associated with muscle damage (Ankyrin repeat domain-containing protein 2, down-regulated in CWP), muscle recovery (Alpha-crystallin B chain, up-regulated in CWP) stress and inflammation (carbonic anhydrase 3, up-regulated in CWP). The contractile and structural proteins found have been associated with various types of myopathies (Actin alpha skeletal muscle, up-regulated, Troponin T slow skeletal muscle and Desmin, down-regulated in CWP). Conclusions In conclusion, the expression of these proteins belonging to the protein groups, contractile, stress and inflammatory, structural, and metabolic, suggests abnormalities and alterations in the myalgic trapezius muscle.

Aims The aims of this study are to investigate the differences in (1) heat pain threshold, (2) pain and temperature perception of the TGI and (3) the sensation of capsaicin between subjects with high and low expression of the serotonin transporter (5-HTT). In addition the effects of capsaicin sensitization on the thermal grill illusion are studied. Methods A total of 80 healthy subjects are selected on the basis of their tri-allelic 5-HTTLPR genotype. Threshold for heat pain is examined and pain and unpleasantness of cutaneous capsaicin application are rated on visual analog scales (VAS). The sensory dimensions of the TGI (before and after capsaicin) is determined i.e. description of temperature (burning hot, hot, neutral, cold or freezing cold) and potential pain and intensity of cold and warmth are rated on respective VAS-scales. Results The study is ongoing. We expect that the low expression group has a higher heat pain threshold and rates the TGI and capsaicin less painful. The capsaicin sensitization lowers the heat pain threshold and increases the cold pain threshold. Therefore we hypothesize a lower rating of the TGI, determined as a lower heat VAS-score. Conclusions No conclusions yet. Preliminary results from the study will be presented at the SASP14.

Aims Previous studies have suggested that many inflammatory cytokines, including interleukin (IL)-1α, may be associated with lumbar radicular pain after disc herniation. In the present study, we examined how variability of the IL-1α gene affects pain intensity and the pressure pain threshold (PPT) in patients with symptomatic disc herniation. Methods A total of 121 patients with lumbar radicular pain due to disc herniation were recruited from Oslo University Hospital, Norway, and followed up at 6 weeks and 12 months. The primary outcome measures were pain intensity scores for the lower back and legs using a visual analog pain scale (VAS) and PPT for the gluteal muscles. Genotyping was carried out using a predesigned TaqMan assay for IL-1α rs1800587. The effect of the IL-1α genotype on the VAS and PPT was analyzed by repeated measure analyses of variance. Results The IL-1α gene C>T polymorphism rs1800587 affected VAS and PPT scores in patients with symptomatic disc herniation. Patients with the CT/TT genotype reported a higher VAS leg pain intensity ( p = 0.002) and also a lower PPT in the gluteal muscles (left p = 0.016; right p = 0.016) compared to patients with the CC genotype during 1 year of follow-up. Conclusions The present data show that the IL-1α CT/TT genotype rs1800587 may be associated with increased pain intensity, and corresponding reduced PPT during the first year after disc herniation.

Aims Since the insertion of MD probes causes an acute tissue trauma, analyses of microdialysates during this period has previously been disregarded in favour of waiting until stable baselines are achieved. The aim of this study is to compare the levels of NAEs in women with chronic widespread pain (CWP) to the healthy controls (CON) during the tissue trauma period. Methods 18 women with CWP were included in this study. Inclusion criteria were female sex, age range 20–65 years, and widespread pain according to the American College of Rheumatology (ACR) classification. 20 CON were recruited. Inclusion criteria were female sex age range 20–65 years, and pain-free. All participants were examined by a standard and validated clinical examination of the upper extremities. MD was conducted in trapezius muscle and dialysate were sampled every 20 min, and the samples of interest in this study were collected in the two first hour after catheter insertion. CMA 63 (catheter: membrane 30 mm length, 0.5 mm diameter, 20 kDa cut-off, flow rate: 5 μl/min) was used. The levels of NAEs were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS). Results Oleoylethanolamine (OEA) and Palmitoylethanolamine (PEA) levels were significantly higher in CWP compered to CON during tissue trauma period (Mann–Whitney U -test: P > 0.001 for OEA and P ≤ 0.05 for PEA). Conclusions Previous biochemical studies of patients with CWP have often focused on sensitizing substances. Here we investigated the levels of lipid signaling molecules, with anti-inflammatory and pain-relieving properties, during acute tissue trauma. The results demonstrate that the levels of OEA and PEA differ significantly between CWP and CON. A better understanding of the interplay between these lipids and peripheral pain signaling might provide new therapeutic opportunities for patients with CWP.

Aims To gain an understanding of the concept of quality pain management (QPM) in the hospital setting, and to define the concept. Methods A concept evaluation based on the method by Morse and colleagues was done. The literature was searched according to selected key words in five databases. Over 5000 articles were found but data were limited to 37 articles directly related to both quality and pain management in adults in the hospital setting, and published in peer-reviewed journals or by an official organization. Data were extracted from these articles and then synthesized according to definition, characteristics, boundaries, preconditions, and outcomes of QPM. Results QPM is a multidimensional concept that is commonly used but remains vaguely defined. A common understanding of the concept is nonetheless evident in the literature. QPM refers to the structure, process, and outcomes of care rooted in equitable, effective, patient-centered, safe, and efficient services. The structure encompasses competent staff and staff accountability, organizationally supported evidence-based policies, and access to interprofessional and specialized care. The process consists of screening, assessing and reassessing pain, individualized and evidence-based treatment, communication of pain and pain treatment, and patient and family education. Finally, outcomes include increase in patient satisfaction, reduced pain severity, less functional interferences, and decrease in both prevalence and severity of adverse effects from pain or its treatment. Conclusions QPM is a complex concept that despite common use lacks a clear definition. The relationship between structure, process, and outcome needs to be studied in order to improve QPM. The conceptual model put forward in this study needs to be further refined and tested.