Volume 23, Issue 1

Background and aims Muscle related temporomandibular disorders (myogenous TMD), one of the most common orofacial pain conditions, is characterized by facial pain and often accompanied by jaw movement limitations. Although the underlying biological mechanisms are still unclear, a cluster of proteins and peptides is assumed to be involved in the pathophysiology. These proteins and peptides may be measured in a simple non-invasive saliva sample. This work investigated whether saliva can be used to sample algogenic substances that can serve as molecular biomarkers for TMD myalgia. Methods Saliva and blood samples were collected from healthy individuals (n=69) and patients diagnosed with TMD myalgia (n=39) according to the Diagnostic Criteria for TMD. Unstimulated and stimulated whole, parotid, and sublingual saliva were analysed. The protein profiles were investigated using two-dimensional gel electrophoresis followed by identification with liquid chromatography tandem mass spectrometry. Levels of nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), and brain derived neuro-tropic factor (BDNF) were determined using western blotting based technology and multiplex electro-chemiluminescence assay panel. Glutamate, serotonin, and substance p (SP) were determined using commercially available methods. Results Different saliva collection approaches resulted in significant differences in the protein profile as well as in the expression of NGF, BDNF, CGRP, SP, and glutamate. Stimulated whole saliva showed least variability in protein concentration (35%) and was correlated to plasma levels of glutamate. Unlike SP and glutamate, NGF and BDNF expressed a rhythmic variation in salivary expression with higher levels in the morning (p<0.05). Patients with a diagnosis of TMD myalgia had significantly higher levels of salivary glutamate but lower salivary NGF and BDNF compared to controls; in addition, the lower NGF and BDNF levels correlated to psychological dysfunction. The quantitative proteomics data revealed 20 proteins that were significantly altered in patients compared to controls. The identified proteins are involved in metabolic processes, immune response, and stress response. Dissimilarities in protein profile and clinical variables were observed between TMD myalgia and myofascial pain. Conclusions The work highlights the importance of consistency in saliva collection approaches, including the timing of the collection. It displayed significant changes in pain specific mediators and protein profile in TMD myalgia and furthermore dissimilarities between subclasses indicating different pathophysiology. After extensive validation, potential salivary biomarkers can be combined with clinical features to better understand and diagnose TMD myalgia.

Objectives Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic. Content This review found no correlations between tendon degeneration, collagen separation or neovascularization and chronic tendon pain. The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations oberserved also in other connective tissues of chronic pain conditions. Healthy, painfree tendons are devoid of nerve fibers in the tendon proper, while innervation is confined to tendon surrounding structures, such as sheaths. Chronic painful tendons exhibit elevated amounts of pain neuromediators, such as glutamate and substance p as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells. Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so called neurogenic inflammation. Summary Chronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, participating in (4) neuro-immune pathways involved in pain regulation. Current treatments that entail the highest scientific evidence to mitigate chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration. Outlook Potential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.

Objectives Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition. Despite recommendations for the inclusion of non-pharmacological treatment in the management of CP/CPPS, the focus has predominantly been on the inclusion of physical therapies with minimal discussion of psychological interventions. Therefore, this systematic review aimed to evaluate peer-reviewed studies of psychological interventions for men with CP/CPPS to determine their therapeutic efficacy and quality of intervention. Methods The review was registered in PROSPERO and based on PRISMA 2020 protocol. The systematic literature search was conducted in six databases. Quantitative studies of psychological intervention for adult men with CP/CPPS that provided outcome measures of pain, quality of life and/or psychological symptoms were reviewed. The Oxford level of evidence and Quality Assessment Tool for Quantitative Studies developed by the Effective Public Health Practice were employed. Results A total of 4,503 studies were reviewed; seven met the inclusion criteria. The included studies were randomised controlled trials, cohort, repeated measures, and case-series studies, with most including combined treatment for CP/CPPS. Cognitive therapy, cognitive behavioural therapy, or paradoxical relaxation training were found to be effective. However, high risks of bias were found in all included studies, limiting the generalisability and reliability of findings. Conclusions Evidence is preliminary but shows promise for psychological treatment either as a combined or standalone treatment for CP/CPPS. However, there is a need to develop research with a more rigorous methodology to evaluate psychological treatments for men with CP/CPPS.

Objectives The prevalence of osteoarthritis (OA) is rising, and pain is the hallmark symptom of OA. Pain in OA is complicated and can be influenced by multiple joint-related factors and factors related to, e.g., physiological, epigenetic, and pain sensory profiles. Increasing evidence suggests that a subset of patients with OA are pain sensitive. This can be assessed using quantitative sensory testing (QST). Common treatments of OA are total knee arthroplasty (TKA) and administration of 3-weeks of non-steroidal anti-inflammatory drugs (NSAIDs), which provide pain relief to many patients with OA. However, approx. 20% of patients experience chronic postoperative pain after TKA, whereas NSAIDs provide an average pain relief of approx. 25%. The current topical review focuses on the emerging evidence linking pretreatment QST to the treatment response of TKA and NSAID treatments. Content MEDLINE was systematically searched for all studies from 2000 to 2022 on pretreatment QST, TKA, and NSAIDs. Pre-clinical studies, reviews, and meta-analyses were excluded. Summary Currently, 14 studies on TKA and four studies on NSAIDs have been published with the aim to attempt prediction of the treatment response. The QST methodologies in the studies are inconsistent, but 11/14 (79%) studies on TKA and 4/4 (100%) studies on NSAIDs report statistically significant associations between pretreatment QST and chronic postoperative pain after TKA or analgesic effect after NSAID treatment. The strength of the associations remains low-to-moderate. The most consistent pretreatment QST predictors are pressure pain thresholds, temporal summation of pain, and conditioned pain modulation. Outlook The use of QST as predictors of standard OA treatment is interesting, but the predictive strength remains low-to-moderate. A transition of QST from a research-based setting and into the clinic is not advised until the predictive strength has been improved and the methodology has been standardized.

Objectives Neurological complications including pain are common after treatment for breast cancer. This prospective study investigated the symptoms, intensity and interference of chemotherapy-induced peripheral neuro-pathy. (CIPN) in the feet and hands compared to surgery- and radiation-induced neuropathy in the breast and upper arm. Methods Consecutive patients referred to surgery for breast cancer were included in a prospective study and completed a questionnaire at baseline and a follow-up questionnaire and interview after one year. CIPN was assessed with the CIPN20 questionnaire and the Michigan Neuropathy Screening Instrument questionnaire (MNSIq). Pain intensity was rated on a numeric rating scale (NRS, 0–10). Results In total 144 patients were included, of which 73 received chemotherapy. At one-year follow-up, symptoms of polyneuropathy were more common in patients treated with chemotherapy. Tingling or numbness in the feet in those treated/not treated with chemotherapy was reported by 44 (62%) and 15 (21%), respectively. Pain was present in 22 (30%) and 10 (14%), respectively. Pain in the area of surgery was reported by 66 (46%). Although less common, pain in the feet in those treated with chemotherapy was rated as more intense and with more daily life interference than pain in the surgical area (NRS 5.5 (SD 1.9) vs. 3.1 (SD 1.9). Conclusions Neurological complications including pain following surgery and chemotherapy represent a burden to breast cancer survivors. In those who had received chemotherapy, pain in the feet was less common than pain in the surgical area, but pain in the feet was more intense and had a higher interference with daily life. Our study emphasizes the need for either baseline data or a control population for improved estimation of the presence and severity of CIPN and pain from questionnaires.

Objectives Neuropeptide Y is associated with stress in animal and human laboratory studies. However, data from clinical studies are scarce and no clinical longitudinal studies have been published. The aim of this clinical study was to assess the possible association between changes in the levels of pain, depression, and stress measures, on the one hand, and plasma neuropeptide Y levels, on the other. Methods Forty-four women with the fibromyalgia syndrome were exposed to a Cognitive Behavioral Therapy intervention. Levels of the plasma neuropeptide Y as well as pain, depression, and stress measures were obtained at the start and at the end of the intervention, and after a further six month follow-up. Based on these data, a before-and-after analysis was performed. Results Almost all measures of pain, depression, and stress improved during the study; specifically, variables measuring life control (coping), depression, and stress-related time urgency improved significantly. Moreover, during the same time period, the mean plasma neuropeptide Y level was reduced from 93.2 ± 38.8 fmol/mL before the Cognitive Behavioral Therapy to 75.6 ± 42.9 fmol/mL (p<0.001) at the end of the study. Conclusions After exposure to a Cognitive Behavioral Therapy intervention, levels of most of the pain, depression, and stress measures improved, half of them significantly, as did the levels of neuropeptide Y. This circumstance indicates a possible functional relationship between pain-depression-stress and neuropeptide Y.

Objectives Although patients’ complaints suggest polyneuropathy (PNP) and neuropathic pain, routine investigations do not always support the diagnosis. Assessing two-point-pain discrimination thresholds (2ptDT) and quantify body representation disturbances might be useful to close this diagnostic gap. Methods Pinprick pain and laser-heat pain perception thresholds and 2ptDT on hands, forearms, lower legs and feet were obtained in 20 PNP patients (mean age: 57.6 ± 13.9) and 20 healthy subjects (mean age: 50.6 ± 4.7 years). Body representation disturbances were assessed by self-estimating feet size and the Bath CRPS body perception disturbances questionnaire adapted for PNP. Results Pain perception thresholds and laser-heat pain 2ptDT were unaltered, but patients had higher pinprick pain 2ptDT then the healthy subjects. The 2ptDT for pinprick at the hands discriminate best between groups (U-test; p=0.001). Furthermore, patients estimated their feet longer than they are. In subsequent multivariate discriminant analyses, 2ptDT for pinprick pain at the hands, 2ptDT for laser-heat pain and the perception thresholds for laser-heat pain at the feet classified 85% of PNP vs. HC correctly. The combination of 2ptDT for pinprick pain at the hands, pinprick pain perception thresholds at the calves and foot length estimation differentiates painful vs. non-painful PNPs correctly in 90% of the cases. Conclusions Testing 2ptDT for painful pinprick stimuli at the hands and asking for foot length estimation might add to diagnostic accuracy in painful PNP.

Objectives We aimed to investigate whether coexistent self-reported neck pain influences cephalic and extracephalic pain sensitivity in individuals with migraine and tension-type headache (TTH) in relation to diagnosis and headache frequency. Methods A population of 496 individuals completed a headache interview based on ICHD criteria, providing data collected by self-administered questionnaires, assessments of pericranial total tenderness score (TTS) and pressure pain thresholds (PPT). Stimulus-response (SR) functions for pressure vs. pain were recorded. Presence of neck pain in the past year was assessed by the self-administered questionnaire. We categorized participants by primary headache type. We also categorized participants into 3 groups by headache frequency: chronic (≥15) or episodic (<15 headache days/month) headache and controls. TTS, PPTs and the area under the SR curve were compared between subgroups using Generalized Linear Models with pairwise comparisons controlling for age and sex. Results Individuals with chronic followed by episodic headache had higher TTS than controls (overall p≤0.001). The difference between chronic and episodic headache subgroups was significant in the group with neck pain (p≤0.001) but not in the group without neck pain. In individuals with neck pain, mean TTS was higher in coexistent headache (migraine and TTH), 23.2 ± 10.7, and pure TTH, 17.8 ± 10.3, compared to pure migraine, 15.9 ± 10.9 and no headache 11.0 ± 8.3 (overall p<0.001). Temporal and finger PPTs did not statistically differ among the chronic headache, the episodic headache and controls in individuals with and without neck pain. Temporalis and trapezius SR-functions showed that tenderness was increased in individuals with chronic headache to higher degree than in those with episodic headache, and more so in those with neck pain. Conclusions Coexistent neck pain is associated with greater pericranial tenderness in individuals with chronic headache and to a lesser degree in those with episodic headache. Sensitization may be a substrate or consequence of neck pain and primary headache, but a longitudinal study would be needed for further clarification.

Objectives This study investigated clinician experience of patient use of metaphors in chronic pain communication. Methods Interviews were conducted with eighteen Australian clinicians working with chronic pain patients, age range 26–64 years ( M =46.6), 50% female, experience working in chronic pain ranging from 2 to 27 years ( M =11.16). Results Thematic Analysis yielded four key themes: Metaphor as communicative tool, Metaphor as clue, Metaphor as obstacle, and Metaphor use in treatment. Clinicians identified metaphor as an important tool for patients to communicate their pain experience, whilst acknowledging that it could at times be unhelpful to patients. Metaphor was seen to contain useful information for clinicians and possess utility in assessment and treatment. Conclusions Metaphors play a significant role in chronic pain consultations, enabling clinician insight into pain type, psychopathology, and patient pain understanding. Metaphor in treatment phases may be underutilised. Clinicians should encourage patient metaphor use in chronic pain communication.

Objectives Chronic vulvar pain (CVP) is pain in the vulvar area exceeding three months of duration. Previous studies have reported a prevalence of 7–8% in the general population and observed an association between CVP and other chronic pain, affective disorders and early life stressors. The aim of this study was to estimate the prevalence of CVP among gynecological outpatients and to explore its association with child sexual abuse, comorbid fibromyalgia and mental health. Methods We conducted a questionnaire-based cross-sectional study among consecutive women attending an unselected general gynecological outpatient clinic at St Olav’s University Hospital, Trondheim, Norway, during the period August 1st, 2017, to June 30th, 2018. CVP was defined as having experienced either vulvar burning, sharp pain or allodynia for three months or more within the previous year. Fibromyalgia was defined as widespread pain in the past six months in conjunction with a symptom severity score ≥5 on the fibromyalgia symptom severity score inventory, an ordinal scale from zero to 12. We collected information on sexual coercion experience and assessed mental health with the mental health inventory (MHI-5) of the SF-36 health survey, which yields a zero to five scale. Results Of 1,125 questionnaires distributed, 810 (72%) were returned, and 762 (68%) included in final analyses. Among these, 130 (17.1%) reported CVP within the previous year and 92 (16.7%) were classified as suffering from fibromyalgia. Fibromyalgia was associated with CVP (adjusted OR of 1.8, 95% CI 1.1–3.1). Child sexual abuse was reported by 96 (13.1%) and was associated with CVP (adjusted OR 2.0, 95% CI 1.2–3.3). CVP and fibromyalgia were both associated with lower mental health scores; 0.51 and 0.58 points on the MHI-5 scale, respectively. Conclusions Chronic vulvar pain is common among women in a gynecological outpatient clinic and associated with child sexual abuse, comorbid fibromyalgia and worse mental health. Ethical committee number: REK Midt No. 2016/2150.

Objectives Male pelvic pain is a common yet poorly understood condition, strongly influencing quality of life of those affected. Research on psychological and sexual factors is lacking, specifically on younger men in family-forming ages. This study aims to explore psychological and sexual factors related to pelvic pain in younger men (<40 years) through a cross-sectional design. Methods Participants were recruited via social media, and completed a digital survey regarding sexual health and psychological distress (n=2,647). Men with varying levels of pelvic pain were compared on levels of psychological distress and self-reported sexual health. Results Men with pelvic pain (n=369) reported significantly higher levels of catastrophizing, anxiety and premature ejaculation compared to men without pelvic pain. Furthermore, men with higher pain intensity reported significantly higher levels of catastrophizing, anxiety and depressive symptoms compared to men experiencing lower pain intensity. Hierarchical regression analysis revealed catastrophizing and depressive symptoms as significantly predictors of pain intensity. Conclusions These findings underscore the role of psychological factors in male pelvic pain, and points to the need for integrating a psychological understanding for further treatment development.

Objectives To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations. Methods We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the development of insomnia and mild-to-severe chronic LBP and lower limb pain at 11 years follow-up in participants aged ≥32 years and with hsCRP ≤10 mg/L at baseline in 2007–2008: 3,714 without chronic LBP or lower limb pain (sample 1) and 7,892 without insomnia (sample 2). Results Compared to participants without chronic pain, participants with comorbid chronic LBP and lower limb pain had a RR of insomnia of 1.37 (95% CI 1.12–1.66). Compared with participants without insomnia, participants with insomnia did not have an increased risk of comorbid chronic LBP and lower limb pain (RR: 1.06, 95% CI 0.76–1.46); however, participants with insomnia had a RR of chronic LBP of 1.20 (95% CI 1.02–1.42). There was no strong amplifying effect of elevated hsCRP (3.00–10.0 mg/L) on these associations. Conclusions These findings suggest that elevated hsCRP does not amplify the associations between insomnia and mild-to-severe chronic LBP and lower limb pain. Further research using data on the temporal relation between insomnia, chronic pain, and inflammatory responses are required to fully understand the causal pathways.

Objectives Osteoarthritis (OA) and chronic low back pain (CLBP) are common musculoskeletal disorders with substantial patient and societal burden. Nordic administrative registers offer a unique opportunity to study the impact of these conditions in the real-world setting. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study was designed to study disease prevalence and the societal and economic burden in broad OA and CLBP populations. Methods Patients in Sweden, Norway, Finland and Denmark with diagnoses of OA or CLBP (low back pain record plus ≥2 pain relief prescriptions to indicate chronicity) were identified in specialty care, in primary care (Sweden and Finland) and in a quality-of-care register (Sweden). Matched controls were identified for the specialty care cohort. Longitudinal data were extracted on prevalence, treatment patterns, patient-reported outcomes, social and economic burden. Results Almost 1.4 million patients with OA and 0.4 million with CLBP were identified in specialty care, corresponding to a prevalence in the Nordic countries of 6.3 and 1.9%, respectively. The prevalence increased to 11–14% for OA and almost 6% for CLBP when adding patients identified in primary care. OA patients had a higher Elixhauser comorbidity index (0.66 vs. 0.46) and were using opioids (44.7 vs. 10.2%) or long-term nonsteroidal anti-inflammatory drug (NSAIDs) (20.9 vs. 4.5%) more than four times as often as compared to controls. The differences were even larger for CLBP patients compared to their controls (comorbidity index 0.89 vs. 0.39, opioid use 77.7 vs. 9.4%, and long-term NSAID use 37.2 vs. 4.8%). Conclusions The BISCUITS study offers an unprecedented, longitudinal healthcare data source to quantify the real-world burden of more than 1.8 million patients with OA or CLBP across four countries. In subsequent papers we aim to explore among others additional outcomes and subgroups of patients, primarily those patients who may benefit most from better healthcare management.

Objectives Osteoarthritis can have a profound effect on patients’ quality of life. The Burden of Disease and Management of Osteoarthritis and Chronic Low Back Pain: Health Care Utilization and Sick Leave in Sweden, Norway, Finland and Denmark (BISCUITS) study aimed to describe the impact of osteoarthritis on quality of life and determine the association with factors such as pain severity and pharmacological treatment. Methods An observational study was performed with a cross-sectional design including patients with a confirmed osteoarthritis diagnosis enrolled in the National Quality Register for Better management of patients with Osteoarthritis (BOA) between 2016 and 2017 in Sweden. Patient-reported information from BOA was linked to administrative data from three national health registers. The impact of osteoarthritis on quality of life was estimated using the EQ-5D-5L and the first developed experienced-based time-trade-off value set for Sweden to calculate the EQ-5D-5L index scores. EQ-5D-3L index scores were also estimated based on a UK hypothetical value set via a crosswalk method. Ordinary least squares regression models were used to analyse the association between quality of life and potential influencing factors. Results For the 34,254 patients evaluated, mean EQ-5D-5L index score was 0.792 (SD 0.126). Stratifications showed that the index score varied across different levels of pain severity. Increased pain severity and use of pain-relieving medications remained significantly associated with a lower quality of life index score when controlled for potential confounders. The mean EQ-5D-3L index score was 0.605 (SD 0.192). Conclusions This large population-based study from Sweden highlights the substantial impact of osteoarthritis on quality of life amongst different patient groups and that currently available treatment options for osteoarthritis pain do not appropriately address the needs for many osteoarthritis patients.

Objectives Osteoarthritis (OA) is one of the leading causes of disability worldwide. Pain is the most important symptom in OA, driving medical care, disability, reduced functionality, and decreased quality of life. The objective of this study was to describe prescription patterns of difficult-to-treat OA and explore possible predictors of unmet pain relief in Nordic patients. Methods This observational cohort study included patients with a confirmed diagnosis of OA (index date) in specialty care in Sweden, Norway, Finland and Denmark between 1 January 2011 and 31 December 2012 who were followed for up to 5 years. Four subgroups were pre-defined to characterize difficult-to-treat OA: (1) ≥2 chronic comorbidities in the 3-year pre-index period; (2) top 10% of healthcare resource users, 1-year post-index; (3) ≥3 types of prescription pain medications during pre-index period to first year post-index, with ≥30 days between types; (4) having a contraindication to a nonsteroidal anti-inflammatory drug (NSAID). Patient characteristics, prescription patterns and predictors of unmet pain relief (defined as persistent opioid use, using several types of opioids or long-term NSAID use) were analyzed. Results We identified 288,174 OA patients and the average age was 63.5 years at time of diagnosis and 58% of them were female. After 5 years, 35–50% of the patients defined as ‘difficult-to-treat’ had ≥1 prescription of opioids, compared to 20–25% of all OA patients (p-value <0.05). Comorbidities and disability pension were strong predictors of unmet pain relief (p-value <0.001). Conclusions This study shows a substantial use of pain medications (NSAID and opioids) in difficult-to-treat OA patients. These findings suggest that pain may be inadequately managed in a considerable number of patients with OA, particularly those with contraindications to an NSAID. A high comorbid and socioeconomic burden are relevant risk factors among patients who continue to use opioids for a long period of time.

Objectives The purpose of this study was to evaluate longitudinal associations with incident and persistent intrusive pain among rural South Africans. Methods Longitudinal data from two consecutive waves in 2014/2015 and 2018/2019 in Agincourt, South Africa, were analysed. Pain was assessed with the Brief Pain Inventory. Results In all, 683 adults of 3,628 participants without intrusive pain in Wave 1 (19.1%) had incident intrusive pain in Wave 2, 94 adults of 254 participants who had intrusive pain in Wave 1 (38.3%) had intrusive pain at both Wave 1 and 2 (persistent intrusive pain). Furthermore, 358 (7.2%) participants had intrusive pain at baseline. In the fully adjusted model for people without intrusive pain at baseline, the study found that obesity (AOR: 1.31, 95% CI: 1.05–1.63), depressive symptoms (AOR: 1.67, 95% CI: 1.34–2.08), PTSD (AOR: 1.71, 95% CI: 1.19–2.45), and poor sleep quality (AOR: 1.30, 95% CI: 1.04–1.62) were positively associated with incident intrusive pain. Older age was positively, and male sex and daily alcohol use were negatively associated with incident intrusive pain. Furthermore, in the final adjusted logistic regression model, this study found that older age was positively, and underweight, overweight, and high sedentary behavior were negatively associated with persistent intrusive pain. Conclusions Several modifiable risk factors for incident and/or persistent intrusive pain were identified.

Objectives In England, the prevalence of chronic pain is higher in more deprived compared to less deprived areas. Patients in such areas also experience more severe and disabling pain than those in less deprived areas. However, little is known about whether the distribution of services for chronic pain reflect these ranging levels of need. This study examines how the types of services available for chronic pain patients vary between healthcare providers in England, serving areas of differing deprivation. Methods National guidelines regarding primary as well the 8 commonest causes of secondary chronic pain (in the United Kingdom) were used to compile a list of services that have been recommended for supporting chronic pain patients. After searching the websites of 63 randomly selected National Health Service (NHS) Trusts and contacting their pain receptionists and/or secretaries, it was recorded whether the Trusts were providing each of these recommended chronic pain services. Mean Index of Multiple Deprivation 2019 scores were used to compare deprivation levels of areas covered by each NHS Trust. Results There was no significant difference in the overall number of types of chronic pain services provided by NHS Trusts serving areas of differing deprivation, but deprived areas were being disadvantaged with regards to specific services. These areas were significantly (p<0.05) less likely to have occupational therapy, return-to-work programmes, and hand therapy services. Areas with fewer types of professionals (≤3) in their pain multidisciplinary team were also significantly (p<0.05) more deprived than those with more types (>3). Conclusion There are significant differences in the provision of certain types of chronic pain services between areas of differing deprivation. Similar research across Europe is recommended to inform policy to combat the widespread chronic pain related health inequalities.

Objectives Paradoxical sensations, known as thermal pain illusions, can be evoked by painful cold-heat pulse stimulation. They may provide diagnostic value; however, the possible interaction between conditioned pain modulation and thermal pain illusions has not been explored. The present study examined: (1) whether conditioned pain modulation could be induced by alternating tonic painful cold-heat pulse stimulation; and (2) whether the presence of thermal pain illusions during the conditioning stimulus influences the degree of conditioned pain modulation. Methods This study was approved by the Ethics Committee of Meikai University (A1507). Conditioned pain modulation was provoked using alternating painful cold-heat pulses delivered at 20-s intervals applied to the forearm. Thermal pain illusions were qualitatively evaluated, and conditioned pain modulation was assessed quantitatively using the pressure pain threshold as a test stimulus. Differences in the conditioned pain modulation effect between the participants who experienced thermal pain illusions and those who did not were analysed using Student’s t -test. Results A significant positive conditioned pain modulation effect (51.0 ± 4.7%, overall effect) was detected. There was no significant difference in conditioned pain modulation between the participants who experienced thermal pain illusions and those who did not (44.3 ± 6.0% and 55.5 ± 6.8%, respectively; p = 0.255). Conclusions Conditioned pain modulation induced by alternating painful conditioning cold-heat pulse stimulation was identical during the conditioning stimulation in volunteers with and without thermal pain illusions. Conditioning cold-heat pulse stimulation is useful to evaluate conditioned pain modulation. Moreover, conditioned pain modulation is not influenced by the presence of thermal pain illusions, indicating partially different underlying supraspinal, neuronal networks.

Objectives Peripheral neuropathies that occur secondary to nerve injuries may be painful or painless, and including a low-grade inflammation and pro-inflammatory cytokines associated with both regeneration and damage of peripheral nerve cells and fibers. Currently, there are no validated methods that can distinguished between neuropathic pain and painless neuropathy. The aim of this study was to search for proinflammatory and anti-inflammatory proteins associated with pain and experimental pain sensitivity in subjects with surgeon-verified nerve injuries in the upper extremities. Methods One hundred and thirty-one subjects [69 with neuropathic pain, NP; 62 with painless neuropathy, nP] underwent a conditioned pain modulation (CPM) test that included a cold pressor task (CPT) conducted with the non-injured hand submerged in cold water (4 °C) until pain was intolerable. CPM was assessed by pain ratings to pressure stimuli before and after applying the CPT. Efficient CPM effect was defined as the ability of the individual’s CS to inhibit at least 29% of pain (eCPM). The subjects were assigned to one of two subgroups: pain sensitive (PS) and pain tolerant (PT) after the time they could tolerate their hand in cold water (PS<40 s and PT=60 s) . Plasma samples were analyzed for 92 proteins incorporated in the inflammation panel using multiplex Protein Extension Array Technology (PEA). Differentially expressed proteins were investigated using both univariate and multivariate analysis (principal component analysis-PCA and orthogonal partial least-squares discriminant analysis-OPLS-DA). Results Significant differences in all protein levels were found between PS and PT subgroups (CV-ANOVA p<0.001), but not between NP and nP groups (p=0.09) or between inefficient CPM (iCPM) and eCPM (p=0.53) subgroups. Several top proteins associated with NP could be detected using multivariate regression analysis such as stromelysin 2 (MMPs), interleukin-2 receptor subunit beta (IL2RB), chemokine (C-X-C motif) ligand 3 (CXCL3), fibroblast growth factor 5 (FGF5), chemokine (C-C motif) ligand 28 (CCL28), CCL25, CCL11, hepatocyte growth factor (HGF), interleukin 4 (IL4), IL13. After adjusting for multiple testing, none of these proteins correlated significantly with pain. Higher levels of CCL20 (p=0.049) and CUB domain-containing protein (CDCP-1; p=0.047) were found to correlate significantly with cold pain sensitivity. CDCP-1 was highly associated with both PS and iCPM (p=0.042). Conclusions No significant alterations in systemic proteins were found comparing subjects with neuropathic pain and painless neuropathy. An expression of predominant proinflammatory proteins was associated with experimental cold pain sensitivity in both subjects with pain and painless neuropathy. One these proteins, CDC-1 acted as “molecular fingerprint” overlapping both CPM and CPT. This observation might have implications for the study of pain in general and should be addressed in more detail in future experiments.

Objectives Emotional profile is involved in the experience of chronic pain related to endometriosis. Following the Örebro Model of Behavioral Emotion Regulation of Pain, the aim of this study was to understand the processes involved in the psychological adaptation to pain experienced during menstruations in women either diagnosed or not diagnosed with endometriosis. Methods The study was conducted on a sample of 545 women, either diagnosed with endometriosis or not, during their menstruations. Functional repercussions and intensity of pain, catastrophic thinking, difficulties in emotional regulation and emotional distress were assessed through an online questionnaire. Structural equation modeling (SEM) was carried out. Results Women diagnosed with endometriosis experience more suffering than women who have not had such a diagnosis. The model we adapted from Örebro’s model fits the data well. A differential effect is observed regarding the retroactive effect of depression on pain. Although emotional distress increases functional repercussions among women both with and without the diagnosis, growing pain intensity only occurs among those without. Conclusions A woman presenting pain during menstruation faces emotional regulation issues that make her more vulnerable to the development of emotional distress. Pain impacts emotional distress, but emotional distress does not impact pain among women for whom the origin of the pain was known (i.e., a diagnosis of endometriosis). Having a diagnosis allows women to externalize the origin of their pain, attributing it to the disease and not to their psychological state.

Objectives Cluster headaches are an intensely painful and debilitating headache disorder. Conventional management includes abortive and preventative agents. A fifth of patients with chronic cluster headaches can be refractory to conventional treatment. Cluster headache can develop following whiplash trauma to the head and neck. Case Presentation Three patients were referred to a tertiary pain medicine unit in a university teaching hospital with treatment-resistant chronic cluster headache. They were treated with a novel intervention namely, ultrasound-guided intermediate cervical plexus block with depot methylprednisolone. Patient one reported chronic cluster headache for three years. Patient two reported episodic cluster headache that appeared to be evolving into chronic cluster headache. Patient three reported bilateral cluster headache following a motor vehicle accident. Intermediate cervical plexus block provided significant and durable relief in three patients with treatment resistant chronic cluster headache. Conclusions The novel intervention may have played a role in aborting and preventing chronic cluster headaches.

Objectives This report seeks to highlight a pitfall that may be encountered in the management of patients with trigeminal neuralgia with imaging showing both neurovascular conflict as well as tumors. Case presentation A case of a 53 year old male with simultaneous neurovascular conflict and a vestibular schwannoma with trigeminal neuralgia is presented and the management is discussed with reference to managing this particular subset. Pain was noted to be likely generated by neurovascular conflict and not by the tumor, which is usually not the case. Conclusions It is suggested that in such cases, microvascular decompression should always be performed in addition to removal of the tumor.

Objectives The Tampa Scale of Kinesiophobia (TSK) is a valid and reliable tool to assess somatic focus and activity avoidance in patients. Currently, the test-retest reliability and measurement error for the Danish version is unknown. The aim of the study was to determine standard error of measurement (SEM) and smallest detectable change (SDC) for three Danish lengths of the TSK in patients with chronic pain. Methods Waiting-list patients (n = 77) completed the TSK-17 twice from home with a test interval between 7 and 14 days. Based on COSMIN recommendations, the test-retest reliability was estimated using intraclass correlation coefficient (ICC 2,1 ), and measurement error in terms of standard error of measurement (SEM agreement ) and SDC95% were calculated. Results All three versions showed good test-retest reliability with ICC 2,1 -values (CI95%) of 0.86(0.79–0.91), 0.88(0.82–0.92) and 0.87(0.81–0.92) for the TSK-17, TSK-13, and TSK-11. The SEM-values were 3.08, 2.42 and 2.10 respectively and SDC95%-values were 8.53, 6.71 and 5.82. Conclusions The Danish versions of TSK-11, TSK-13 and TSK-17 showed good to excellent test-retest reliability. SEM and SDC95% values in patients with chronic pain are reported. The TSK-11 did not show systematic bias between test and retest and may be preferred to minimize responder burden.