Effects of interdisciplinary pain rehabilitation programs on neuropathic and non-neuropathic chronic pain conditions - a registry-based cohort study from Swedish Quality Registry for Pain Rehabilitation (SQRP).

BACKGROUND AND AIM: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Pharmacological treatments for neuropathic pain often fail despite following guidelines. Interdisciplinary Pain Rehabilitation Programs (IPRP) are an effective intervention for chronic pain conditions. Little research has investigated whether IPRP can benefit patients with chronic neuropathic pain compared to other chronic pain conditions. This study assesses the real-world effects of IPRP on patients with chronic neuropathic pain compared to non-neuropathic patients using Patient-Reported Outcome Measures (PROMs) available in the Swedish Quality Registry for Pain Rehabilitation (SQRP). METHODS: A neuropathic group of patients (n = 1,654) were identified in two steps. This group was compared to a non-neuropathic group (n = 14,355) composed of common diagnoses (low back pain, fibromyalgia, whiplash associated disorders, and Ehlers-Danlos Syndrome) in relation to background variables, three overall outcome variables, and mandatory outcome variables (pain intensity, psychological distress symptoms, activity/participation aspects and health-related quality of life variables). Of these patients 43-44% participated in IPRP. RESULTS: At assessment, the neuropathic group reported significantly (with small effect sizes (ES)) more physician visits the previous year, older age, shorter pain durations, and less spatial extent of the pain (moderate ES). Moreover, for the 22 mandatory outcome variables, we found only clinically insignificant differences according to ESs between the groups. For patients participating in IPRP, the neuropathic group displayed equal or in some cases slightly superior results compared to the non-neuropathic group. DISCUSSION AND CONCLUSION: After assessing the real-world effects of IPRP, this large study found that neuropathic pain patients can benefit from the IPRP intervention. Both registry studies and RCTs are needed to better understand which patients with neuropathic pain are most suitable for IPRP and to what extent special considerations need to be made for these patients within the framework of IPRP.

Internet-Delivered Cognitive Behavioral Therapy for Insomnia Comorbid With Chronic Pain: Randomized Controlled Trial.

BACKGROUND: Patients with chronic pain often experience insomnia symptoms. Pain initiates, maintains, and exacerbates insomnia symptoms, and vice versa, indicating a complex situation with an additional burden for these patients. Hence, the evaluation of insomnia-related interventions for patients with chronic pain is important. OBJECTIVE: This randomized controlled trial examined the effectiveness of internet-based cognitive behavioral therapy for insomnia (ICBT-i) for reducing insomnia severity and other sleep- and pain-related parameters in patients with chronic pain. Participants were recruited from the Swedish Quality Registry for Pain Rehabilitation. METHODS: We included 54 patients (mean age 49.3, SD 12.3 years) who were randomly assigned to the ICBT-i condition and 24 to an active control condition (applied relaxation). Both treatment conditions were delivered via the internet. The Insomnia Severity Index (ISI), a sleep diary, and a battery of anxiety, depression, and pain-related parameter measurements were assessed at baseline, after treatment, and at a 6-month follow-up (only ISI, anxiety, depression, and pain-related parameters). For the ISI and sleep diary, we also recorded weekly measurements during the 5-week treatment. Negative effects were also monitored and reported. RESULTS: Results showed a significant immediate interaction effect (time by treatment) on the ISI and other sleep parameters, namely, sleep efficiency, sleep onset latency, early morning awakenings, and wake time after sleep onset. Participants in the applied relaxation group reported no significant immediate improvements, but both groups exhibited a time effect for anxiety and depression at the 6-month follow-up. No significant improvements on pain-related parameters were found. At the 6-month follow-up, both the ICBT-i and applied relaxation groups had similar sleep parameters. For both treatment arms, increased stress was the most frequently reported negative effect. CONCLUSIONS: In patients with chronic pain, brief ICBT-i leads to a more rapid decline in insomnia symptoms than does applied relaxation. As these results are unique, further research is needed to investigate the effect of ICBT-i on a larger sample size of people with chronic pain. Using both treatments might lead to an even better outcome in patients with comorbid insomnia and chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT03425942; https://clinicaltrials.gov/ct2/show/NCT03425942.

The inflammatory profile of cerebrospinal fluid, plasma, and saliva from patients with severe neuropathic pain and healthy controls-a pilot study.

BACKGROUND: Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. METHODS: The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. RESULTS: We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). CONCLUSIONS: Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.

A Network Analysis of Clinical Variables in Chronic Pain: A Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP).

BACKGROUND: Efforts to identify specific variables that impact most on outcomes from interdisciplinary pain rehabilitation are challenged by the complexity of chronic pain. Methods to manage this complexity are needed. The purpose of the study was to determine the network structure entailed in a set of self-reported variables, examine change, and look at potential predictors of outcome, from a network perspective. METHODS: In this study we apply network analysis to a large sample of people seeking interdisciplinary pain treatment (N = 2,241). Variables analyzed include pain intensity, pain interference, extent of pain, depression, anxiety, insomnia, and psychological variables from cognitive behavioral models of chronic pain. RESULTS: We found that Acceptance, Pain Interference, and Depression were key, "central," variables in the pretreatment network. Interestingly, there were few changes in the overall network configuration following treatment, specifically with respect to which variables appear most central relative to each other. On the other hand, Catastrophizing, Depression, Anxiety, and Pain Interference each became less central over time. Changes in Life Control, Acceptance, and Anxiety were most strongly related to changes in the remainder of the network as a whole. Finally, no network differences were found between treatment responders and non-responders. CONCLUSIONS: This study highlights potential future targets for pain treatment. Further application of a network approach to interdisciplinary pain rehabilitation data is recommended. Going forward, it may be better to next do this in a more comprehensive theoretically guided fashion, and ideographically, to detect unique individual differences in potential treatment processes.

Outcomes of Interdisciplinary Pain Rehabilitation Across Subgroups of the Multidimensional Pain Inventory - A Study From the Swedish Quality Registry for Pain Rehabilitation.

INTRODUCTION: The Multidimensional Pain Inventory (MPI) is frequently used in the assessment of chronic pain. Three subgroups have been derived from MPI: adaptive coper (AC), dysfunctional (DYS), and interpersonally distressed (ID). The primary aim of this study was to examine whether outcome of Interdisciplinary Multimodal Pain Rehabilitation Programs (IMMRPs) differed across the MPI subgroups. METHODS: Patients with chronic pain (N = 34,513), included in the Swedish Quality Registry for Pain Rehabilitation, were classified into MPI subgroups and a subset that participated in IMMRPs (N = 13,419) was used to examine overall treatment outcomes using a previously established Multivariate Improvement Score (MIS) and 2 retrospective patient-evaluated benefits from treatment. RESULTS: The subgroups differed on sociodemographic characteristics, pain duration, and spatial spreading of pain. DYS and ID had the best overall outcomes to MIS. AC had the best outcomes according to the 2 retrospective items. Transition into other subgroups following IMMRP was common and most prominent in DYS and least prominent in AC. CONCLUSION: The validity of the MPI subgroups was partially confirmed. DYS and ID had the most severe clinical presentations at baseline and showed most improvement following IMMRP, but overall severity in DYS and ID at post-treatment was still higher than in the AC group. Future studies should examine how processes captured by MPI interact with neurobiological, medical, sociodemographic, and adaptation/coping factors and how these interactions impact severity of chronic pain and treatment outcome.

Proteomic studies of common chronic pain conditions - a systematic review and associated network analyses.

INTRODUCTION: The lack of biomarkers indicating involved nociceptive and/or pain mechanisms makes diagnostic procedures problematic. Clinical pain research has begun to use proteomics. AREAS COVERED: This systematic review covers proteomic studies of chronic pain cohorts and in relation to clinical variables. Searches in three databases identified 96 studies from PubMed, 161 from Scopus and 155 from Web of Science database. Finally, 27 relevant articles were included. Network analyses based on the identified proteins were performed. EXPERT OPINION: Small pain cohorts were investigated and the number of studies per diagnosis and tissue is small. The use of proteomics in chronic pain research is exploratory and larger proteomic studies are needed. It will be necessary to standardize the descriptions of the pain cohorts investigated. There is a need to identify the mechanisms underlying the whole clinical presentation of specific chronic pain conditions. Multivariate methods capable of handling and identifying intercorrelated protein patterns must be applied. Rather than focusing on a few proteins, future studies should use network analyses to investigate interactions and biological processes. Proteomics in combination with bioinformatics have a huge potential to identify previously unknown panels of proteins involved in chronic pain and relevant when devising new pain control strategies.

Predictive association between immigration status and chronic pain in the general population: results from the SwePain cohort.

BACKGROUND: Previous studies suggest that immigration may influence the experience of pain. OBJECTIVE: This population-based study examines whether immigration status is associated with chronic pain (CP), chronic widespread pain (CWSP), and severe CP at a two-year follow-up. We also tested mediation by mood status (i.e., anxiety and depression). METHODS: 15, 563 participants from a representative stratified random sample of 34,000 individuals living in south-eastern Sweden completed a postal survey, during 2013-2015, that included the following data: immigration status; presence of CP (pain lasting at least 3 months) and CWSP (a modified classification of widespread pain for use in epidemiological studies); severity of CP based on a numeric rating scale; and depression, anxiety, economic situation, and sociodemographic information. We applied logistic regressions using the generalized estimating equations (GEE), with Swedish-born as the reference group and path analyses models. RESULTS: Compared to the Swedish-born participants (n = 14,093;90%), the immigrants (n = 1470;10%) had an elevated risk of all pain outcomes (CP: odds ratio [OR] = 1.18; 95% confidence interval [CI = 1.04-1.33, CWSP: OR = 1.39; 95% CI: 1.15-1.69 and severe CP: 1.51; 95% CI: 1.23-1.87) after adjustments. Path analyses showed that baseline age, immigrant status, and financial hardship had a significant influence on chronic pain outcomes at follow-up with baseline mood status as the mediator. Immigration status was also associated with age and financial hardship. CONCLUSION: Immigrants may have increased risk of chronic pain, widespread pain, and severe pain and this risk is mediated by mood status. Targeted interventions better tailored to the socio-economic and psychological status of immigrants with chronic pain are warranted.

Patients' experiences of internet-based Acceptance and commitment therapy for chronic pain: a qualitative study.

BACKGROUND: Chronic pain is a globally widespread condition with complex clusters of symptoms within a heterogeneous patient group. Internet-delivered Acceptance and Commitment Therapy (IACT) has shown promising results in the treatment of chronic pain. How IACT is experienced by patients is less well known. Qualitative studies of patients' experiences are needed to further understand factors behind both engagement and negative effects. The aim of this study was to explore how IACT was experienced by chronic pain patients who had participated in a controlled trial. METHODS: Through an open and exploratory approach this study aimed to investigate how IACT was experienced when delivered as a guided self-help program to persons with chronic pain. Eleven participants were interviewed over telephone after completing IACT. RESULTS: Qualitative analysis based on grounded theory resulted in 2 core categories and 8 subcategories. In treatment: Physical and cognitive restraints, Time and deadline, Therapist contact, and Self-confrontation. After treatment: Attitude to pain, Image of pain, Control or Command, and Acting with pain. Individual differences as well as specific conditions of the treatment may explain variations in how the treatment was approached, experienced and what consequences it led to. Therapist guidance and deadlines for homework play complex roles in relation to autonomy and change. CONCLUSIONS: Adjusting treatment content and format based on participants' characteristics, such as expectations, motivation and restraints, might positively affect engagement, autonomy and change. Further research on attrition and negative effects of treatment might clarify what enables chronic pain patients to benefit from IACT. TRIAL REGISTRATION: clinicaltrials.gov (NCT01603797). Registered 22 May 2012. Retrospectively registered.

Protein Signature in Saliva of Temporomandibular Disorders Myalgia.

In the last years, several attempts have been made to study specific biological markers of temporomandibular disorders (TMD). So far, no laboratory tests have been appropriately validated for the diagnosis and prognosis of these disorders. This study aimed to investigate the proteomic profile of the whole stimulated saliva of TMD myalgia patients in order to evaluate potential diagnostic and/or prognostic salivary candidate proteins which could be useful for the management of TMD. Twenty patients diagnosed with TMD myalgia according to the validated Diagnostic Criteria for TMD (DC/TMD) and 20 matched healthy pain-free controls were enrolled. Saliva samples were collected in the morning. Comparative proteomic analysis was performed with two-dimensional gel electrophoresis followed by identification with liquid chromatography-tandem mass spectrometry. Statistical analysis of the quantitative proteomics data revealed that 20 proteins were significantly altered in patients compared to controls. Among these proteins, 12 showed significantly increased levels, and 8 showed significantly decreased levels in patients with TMD myalgia compared to controls. The identified proteins are involved in metabolic processes, immune response, and stress response. This proteomic study shows that the salivary protein profile can discriminate patients with TMD myalgia from healthy subjects, but the protein signature has no correlation with the clinical features of TMD myalgia. Additional studies are needed to validate our observations in additional sample sets and to continue assessing the utility of saliva as a suitable sample for studying processes related to TMD myalgia.

Altered levels of salivary and plasma pain related markers in temporomandibular disorders.

BACKGROUND: Different pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics. METHODS: Patients diagnosed according to the diagnostic criteria for TMD (n = 39), and matched healthy pain-free controls (n = 39) were included. Stimulated whole saliva and plasma samples were collected in the morning. Glutamate was analysed using a colorimetric assay, and 5-HT and SP were analysed by commercially available ELISA. Levels of NGF and BDNF were determined using multiplex electrochemiluminescence assay panel. RESULTS: Patients expressed higher salivary and plasma levels of glutamate (saliva: 40.22 ± 13.23 µmol/L; plasma: 30.31 ± 18.73 µmol/L) than controls (saliva: 33.24 ± 11.27 µmol/L; plasma: 20.41 ± 15.96 µmol/L) (p < 0.05). Salivary NGF (0.319 ± 0.261 pg/ml) and BDNF (3.57 ± 1.47 pg/ml) were lower in patients compared to controls (NGF: 0.528 ± 0.477 pg/ml; BDNF 4.62 ± 2.51 pg/ml)(p's < 0.05). Contrary, plasma BDNF, was higher in patients (263.33 ± 245.13 pg/ml) than controls (151.81 ± 125.90 pg/ml) (p < 0.05). 5-HT was undetectable in saliva. Neither plasma 5-HT, nor SP levels differed between groups. BDNF and NGF concentrations correlated to levels of psychological distress (p < 0.0005). CONCLUSION: The higher levels of salivary and plasma glutamate in patients with TMD-myalgia compared to controls strengthens its importance in the pathophysiology of TMD-myalgia. However, the lack of correlation to pain levels question its role as a putative biomarker. Patients with TMD-myalgia further had lower levels of salivary NGF and BDNF, but higher plasma BDNF. These results and their correlations to psychological distress warrant further investigations.

Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis.

INTRODUCTION: Endometriosis is a gynecological disorder that may cause considerable pelvic pain in women of fertile age. Determining pain mechanisms is necessary in order to optimize the treatment of the disease. The objective of the study was to evaluate pain thresholds in women with persistent pelvic pain with and without confirmed endometriosis, and healthy, unaffected controls, and analyze how pain thresholds in these cohorts related to duration of pelvic pain, quality of life, and symptoms of anxiety and depression. MATERIAL AND METHODS: Pain thresholds for heat, cold and pressure were assessed with quantitative sensory testing on six locations on a reference group of 55 healthy women and on 37 women with persistent pelvic pain who had been admitted for diagnostic laparoscopy on the suspicion of endometriosis. Validated instruments were applied to assess quality of life and symptoms of anxiety and depression. Data were analyzed by means of uni- and multivariate analysis of variance and Spearman's rank-order correlation. RESULTS: The women with persistent pelvic pain had significantly lower pain thresholds compared with the reference women. In the women with pain, no differences were observed in pain thresholds between women with (n = 13) and women without (n = 24) biopsy-proven endometriosis. The duration of pelvic pain correlated significantly positively with reduced pain thresholds, ie, the longer the duration, the more sensitization. In the persistent pelvic pain group, pain thresholds for heat correlated significantly with the Short Form Health Survey 36 dimension of bodily pain, and thresholds for cold correlated with Short Form Health Survey 36 bodily pain and with symptoms of depression. CONCLUSIONS: Our results showed widespread alterations in pain thresholds in women with persistent pelvic pain that are indicative of central sensitization and a time-dependent correlation. Women with pelvic pain and suspicion of endometriosis should probably be treated more thoroughly to prevent or at least minimize the concomitant development of central sensitization.

Positive psychological well-being predicts lower severe pain in the general population: a 2-year follow-up study of the SwePain cohort.

BACKGROUND: Positive psychology indicators like well-being and life satisfaction may play a pivotal role in pain-related outcomes. In this study, we aimed to examine the prospective associations of positive well-being and life satisfaction with pain severity. METHODS AND SUBJECTS: This longitudinal study, with a follow-up of 2 years, included 9361 participants (4266 males, 5095 females; mean age: 52.5 years; SD: 17.5) without and with chronic pain (CP) at baseline. All analyses were stratified by the two sub-cohorts-participants without CP (sub-cohort 1) and participants with CP (sub-cohort 2) at baseline. The predictive associations, assessed using ordinal regression in a Generalized Linear Model, were adjusted for baseline potential confounders and reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: After adjustments, in sub-cohort 1 positive well-being at baseline was associated with lower severe pain at follow-up compared to participants with severe distress (OR: 0.64; 95% CI 0.49-0.84; p < 0.001). In sub-cohort 2, both positive well-being and life satisfaction at baseline were associated with lower severe pain at follow-up compared to participants with severe distress and not satisfied with life (OR: 0.80; 95% CI 0.65-0.98; p = 0.031 and OR: 0.82; 95% CI 0.69-0.96; p = 0.014, respectively). CONCLUSIONS: Positive well-being is predictive of lower pain severity both among participants without and with CP at baseline, whereas life satisfaction was found predictive of lower pain severity only for subjects with CP. Future research should emphasize implementing treatments associated with promoting and maintaining positive well-being and life satisfaction in patients who suffer from chronic pain and in risk populations.

Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study.

BACKGROUND: Post-translational modifications (PTMs) generate a tremendous protein diversity from the ~ 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the central nervous system could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF). In a previous hypothesis-generating study, we reported that seven out of 260 CSF proteins highly discriminated between neuropathic pain patients and healthy controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1-antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment epithelium-derived factor (PEDF). The present study had three aims: (1) To examine the multivariate inter-correlations between all identified isoforms of these seven proteins; (2) Based on the results of the first aim, to characterize PTMs in a subset of interesting proteins; (3) To regress clinical pain data using the 260 proteins as predictors, thereby testing the hypothesis that the above-mentioned seven discriminating proteins and/or the characterized isoforms/fragments of aim (2) would be among the proteins having the highest predictive power for clinical pain data. METHODS: CSF samples from 11 neuropathic pain patients and 11 healthy controls were used for biochemical analysis of protein isoforms. PTM characterization was performed using enzymatic reaction assay and mass spectrometry. Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was applied on the quantified protein isoforms. RESULTS: We identified 5 isoforms of AG, 18 isoforms of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated isoforms of AT were studied in depth. When regressing the pain intensity data of patients, three isoforms of AT, two isoforms of PEDF, and one isoform of angiotensinogen "reappeared" as major results, i.e., they were major findings both when comparing patients with healthy controls and when regressing pain intensity in patients. CONCLUSIONS: Altered levels of fragments and/or glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological processes in the spinal cord of neuropathic pain patients. In particular, we suggest that a putative disease-specific combination of the levels of two different N-truncated fragments of alpha-1-antitrypsin might be interesting for future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

People in states worse than dead according to the EQ-5D UK value set: would they rather be dead?

PURPOSE: Quality-adjusted life years (QALYs) measure health by combining length and quality of life. QALYs constitute the effect side of incremental cost-effectiveness ratios, describing the results of health economic evaluations. The objectives of this study were to (1) investigate the prevalence of states worse than dead (SWD) when using the EuroQol-5D UK value set, and (2) to study to what extent SWDs are reasonable with a starting point in experience-based valuations of health states. METHODS: Data from a Swedish cross-sectional population survey were used. The survey was directed to 10,000 persons 65 years and older and its primary aim was to investigate the prevalence and consequences of chronic pain. The survey included questions reflecting life situation and well-being. Some of these were used in order to characterise people in SWD. RESULTS: SWD were found in 1.8% of the 6611 respondents. The prevalence of SWD increased with advancing age and was more common among women than men. The control questions used indicated that most of the persons being in SWD according to the EQ-5D UK value set most probably would not judge themselves to be in a SWD. CONCLUSIONS: Though negative QALY-weights are not very common, they constitute a non-negligible part of health states in a Swedish population 65 years and older. Prevalence of SWD is higher among women than men and increases with age. From responses to other questions on well-being and life situation, there is reason to doubt the reasonableness of experience-based negative QALY-weights in many cases.

Is excess weight a burden for older adults who suffer chronic pain?

BACKGROUND: Obesity and chronic pain are common comorbidities and adversely influence each other. Advanced age is associated with more comorbidities and multi-morbidities. In this study, we investigated the burden of overweight/obesity and its comorbidities and their associations with chronic pain in a random population sample of Swedish older adults. METHODS: The cross-sectional analysis involved a random sample of a population ≥ 65 years in south-eastern Sweden (N = 6243). Data were collected from a postal questionnaire that addressed pain aspects, body mass index (BMI), and health experiences. Chronic pain was defined as pain during the previous three months. According to the 0-10 Numeric Rating Scale, pain scored ≥7 corresponds to severe pain. Binary logistic regression was used to determine the variables associated to pain aspects. RESULTS: A total of 2633 (42%) reported chronic pain. More obese older adults (BMI ≥30 kg/m2) experienced chronic pain (58%) than those who were low-normal weight (BMI < 25 kg/m2, 39%) or overweight (25 ≤ BMI < 30 kg/m2, 41%). Obese elderly more frequently had pain in extremities and lower back than their peers. In the multivariate model, obesity (Odds Ratio (OR) 1.59, 95% Confidence Interval (CI) 1.33-1.91) but not overweight (OR 1.08, 95% CI 0.95-1.22) was associated with chronic pain. Obesity (OR 1.53, 95% CI 1.16-2.01) was also significantly related to severe pain. We also found other comorbidities - i.e., traumatic history (OR 2.52, 95% CI 1.99-3.19), rheumatic diseases (OR 5.21, 95% CI 4.54-5.97), age ≥ 85 years (OR 1.66, 95% CI 1.22-2.25), and depression or anxiety diagnosis (OR 1.83, 95% CI 1.32-2.53) - showed stronger associations with pain aspects than weight status. CONCLUSION: In older adults, excess weight (BMI 30 or above) is a potentially modifiable factor but not the only risk factor that is associated with chronic pain and severe pain. Future studies should investigate the effectiveness of interventions that treat comorbid pain and obesity in older adults.

Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? - A randomized controlled study.

BACKGROUND: Most people suffering chronic pain are plagued by sleeping difficulties. Cognitive behaviour therapy has produced promising results for insomnia comorbid with chronic pain, but the access to such treatment is often limited. Over the last ten years, interventions aiming to increase cognitive flexibility and physical activity have been assumed to be effective treatments for a variety of conditions, including insomnia and chronic pain. If proven effective, these treatments could constitute the first steps in a stepped care model for chronic pain and insomnia. METHODS: Two hundred ninety-nine chronic pain subjects were randomized to Exercise, ACT-based stress management (ACT-bsm), or an active control group. Two hundred thirty-two participants (78%) received their allocated intervention at least to some extent. These participants were evaluated using mixed model analyses for changes in sleep (Insomnia Severity Index, ISI), pain intensity, depression, and anxiety immediately after treatment, six months and twelve months after treatment. RESULTS: The mixed model analyses revealed that Exercise had a positive effect on insomnia compared with the control group and the effect remained after 12 months. No clear effect (i.e., both for completers and for completers together with treatment non-completers) upon ISI was found for the ACT-bsm. Pain intensity decreased significantly both in the exercise group and in the control group. For the two psychological variables (i.e., symptoms of anxiety and depression) were found significant improvements over time but no group differences. The treatment effects for ISI and pain intensity did not reach clinical significance per definitions presented in other relevant studies. CONCLUSIONS: Beneficial significant effects on insomnia was confirmed in the exercise condition. However, these changes were probably not clinically important. For pain intensity a general decrease was found in the Exercise condition and in the control condition, while no change occurred in ACT-bsm. No group differences were found for the two psychological variables. TRIAL REGISTRATION: The study was registered in Clinical Trials (Trial registration: ClinicalTrials.gov Id: NCT02399644 , 21 January 2015, retrospectively registered).

Controlled, cross-sectional, multi-center study of physical capacity and associated factors in women with fibromyalgia.

BACKGROUND: Health and physical capacity are commonly associated with disease, age, and socioeconomic factors. The primary objective of this study was to investigate the degree to which physical capacity, defined as muscle strength and walking ability, is decreased in women with fibromyalgia (FM), as compared to healthy women, who are matched for age and level of education. The secondary aim was to investigate whether muscle strength and walking ability are associated with age, symptom duration, activity limitations and, Body Mass Index (BMI) in women with FM and control subjects. METHODS: This controlled, cross-sectional, multi-center study comprised 118 women with FM and 93 age- and education-level-matched healthy women. The outcome measures were isometric knee-extension force, isometric elbow-flexion force, isometric hand-grip force, and walking ability. Differences between the groups were calculated, and for the women with FM analyses of correlations between the measures of physical capacity and variables were performed. RESULTS: The women with FM showed 20% (p < 0.001) lower isometric knee-extension force, 36% (p < 0.001) lower isometric elbow-flexion force, 34% (p < 0.001) lower isometric hand-grip force, and 16% lower walking ability (p < 0.001), as compared to the healthy controls. All measures of muscle strength in women with FM showed significant weak to moderate relationship to symptom duration (rs = - 0.23-0.32) and walking ability (rs = 0.25-0.36). Isometric knee-extension force correlated with activity limitations, as measured using the SF-36 Physical function subscale (rs=0.23, p = 0.011). CONCLUSIONS: Physical capacity was considerably decreased in the women with FM, as compared to the age- and education-level-matched control group. All measures of physical capacity showed a significant association with symptom duration. Knee-extension force and walking ability were significantly associated with activity limitations, age, and BMI. It seems important to address this problem and to target interventions to prevent decline in muscle strength. Assessments of muscle strength and walking ability are easy to administer and should be routinely carried out in the clinical setting for women with FM. TRIAL REGISTRATION: ClinicalTrials.gov identification number: NCT01226784 , Oct 21, 2010.

Cuff Pressure Pain Detection Is Associated with Both Sex and Physical Activity Level in Nonathletic Healthy Subjects.

PURPOSE: The aim of this study was to evaluate pressure pain sensitivity on leg and arm in 98 healthy persons (50 women) using cuff algometry. Furthermore, associations with sex and physical activity level were investigated. METHOD: Normal physical activity level was defined as Godin Leisure-Time Exercise Questionnaire (GLTEQ) score ≤ 45 and high activity level as GLTEQ > 45. A pneumatic double-chamber cuff was placed around the arm or leg where a single chamber was inflated. The cuff inflation rate (1 kPa/s) was constant, and pain intensity was registered continuously on a 10 cm electronic visual analogue scale (VAS). The pain detection threshold (PDT) was defined as when the pressure was perceived as painful, and pain tolerance (PTT) was when the subject terminated the cuff inflation. For PTT, the corresponding VAS score was recorded (VAS-PTT). The protocol was repeated with two chambers inflated. RESULT: Only single cuff results are given. For women compared with men, the PDT was lower when assessed in the arm ( P = 0.002), PTTs were lower in the arm and leg ( P < 0.001), and the VAS-PTT was higher in the arm and leg ( P < 0.033). Highly active participants compared with less active had higher PDT ( P = 0.027) in the leg. Women showed facilitated spatial summation ( P < 0.014) in the arm and leg and a steeper VAS slope (i.e., the slope of the VAS pressure curve between PDT and PPT) in the arm and leg ( P < 0.003). CONCLUSION: This study indicates that reduced pressure pain sensitivity is associated both with male sex and physical activity level.

Alterations of anti-inflammatory lipids in plasma from women with chronic widespread pain - a case control study.

BACKGROUND: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro- and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines. METHODS: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants. RESULTS: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found. CONCLUSIONS: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain.

Distinctive subgroups derived by cluster analysis based on pain and psychological symptoms in Swedish older adults with chronic pain - a population study (PainS65+).

BACKGROUND: Improved knowledge based on clinical features of chronic pain in older adults would be valuable in terms of patient-orientated approaches and would provide support for health care systems in optimizing health care resources. This study identifies subgroups based on pain and psychological symptoms among Swedish older adults in the general population and compares derived subgroups with respect to socio-demographics, health aspects, and health care costs. METHODS: This cross-sectional study uses data collected from four registers and one survey. The total sample comprised 2415 individuals ≥65 years old. A two-step cluster analysis was performed. Data on pain intensity, number of pain sites, anxiety, depression, and pain catastrophizing were used as classification variables. Differences in socio-demographics, quality of life, general health, insomnia, and health care costs among the clusters were investigated. Association of the clusters with the above parameters was further evaluated using multinomial logistic regression. RESULTS: Four major clusters were identified: Subgroup 1 (n = 325; 15%) - moderate pain and high psychological symptoms; Subgroup 2 (n = 516; 22%) - high pain and moderate psychological symptoms; Subgroup 3 (n = 686; 30%) - low pain and moderate psychological symptoms; and Subgroup 4 (n = 767; 33%) - low pain and low psychological symptoms. Significant differences were found between the four clusters with regard to age, sex, educational level, family status, quality of life, general health, insomnia, and health care costs. The multinomial logistic regression analysis revealed that Subgroups 1 and 2, compared to Subgroup 4, were significantly associated with decreased quality of life, decreased general health, and increased insomnia. Subgroup 3, compared to Subgroup 4, was associated with decreased general health and increased insomnia. In addition, compared to Subgroup 4, Subgroups 1 and 2 were significantly associated with higher health care costs. CONCLUSIONS: Two high risk clusters of older adults suffering from chronic pain; one mainly based on psychological symptoms and one mainly on pain intensity and pain spread, associated with decreased quality of life and health and increased health care costs were identified. Our findings indicate that subgroup-specific treatment will improve pain management and reduce health care costs.