Det är ofta fruktbart att betrakta långvarig smärta mer som en grupp sjukdomar än som ett symtom. Om man till exempel ser på smärtsam diabetesneuropati som en sjukdom, infinner sig frågan: vad är dess patofysiologi? Vad är det för mekanismer som gör att vissa neuropatipatienter får ont och andra inte? I två biomarkörstudier inom ramen för ett internationellt samarbete publicerade i smärttidskriften Pain [1, 2] har vi analyserat blodprov från patienter med smärtsam respektive icke-smärtsam diabetesneuropati.

Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM n = 18; HC n = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.

Neuropathic pain (NP) is a chronic pain condition resulting from a lesion or disease in the somatosensory nervous system. The aim of this study was to investigate the metabolome in plasma from patients with chronic peripheral, posttraumatic/postsurgical NP compared to healthy controls. Further, we aimed to investigate the correlation between pain intensity and the metabolome in plasma. The metabolic profile in plasma samples from 16 patients with chronic NP and 12 healthy controls was analyzed using a nuclear magnetic resonance spectroscopy method. Information about pain intensity, pain duration, body mass index (BMI), age, sex, and blood pressure were obtained through a questionnaire and clinical examination. Multivariate data analysis was used to identify metabolites significant for group separation and their correlation with pain intensity and duration, BMI, and age. We found 50 out of 326 features in plasma significantly contributing to group discrimination between NP and controls. Several of the metabolites that significantly differed were involved in inflammatory processes, while others were important for central nervous system functioning and neural signaling. There was no correlation between pain intensity and levels of metabolite in NP. These findings indicate that there seems to be peripheral/systemic differences in the metabolic profile between patients with chronic NP and healthy individuals.

Background: Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain.

Methods: Patients (n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA.

Results: Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet (80.1 vs. 56.3; P = 0.02). Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons.

Conclusion: Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted.

Purpose: Fibromyalgia (FM) is a complex pain condition, and exercise is considered the first option of treatment. Few studies have examined the effect of exercise on molecular mechanisms in FM. The aim of this study was to analyze the plasma proteome in women with FM and healthy controls (CON) before and after 15 wk of resistance exercise. This study further investigated whether clinical and exercises-related outcomes correlated with identified plasma proteins in FM.

Methods: Plasma samples from 40 FM/25 CON (baseline) and 21 FM/24 CON (postexercise) were analyzed using shotgun proteomics. Clinical/background data were retrieved through questionnaires. Exercise-related variables and pressure pain thresholds were assessed using standardized instruments. Multivariate statistics were applied to analyze the proteomic profile at baseline and postexercise, and correlation with clinical/exercise-related data.

Results: Fifteen weeks of resistance exercises improved clinical symptoms and muscle strength, and affected circulating proteins related to immunity, stress, mRNA stability, metabolic processes, and muscle structure development in FM. Pressure pain threshold was related to a specific protein profile, with proteins involved in metabolic and immune response. Subgroups of FM based on plasma proteins, FM duration, and improved muscle strength were identified.

Conclusions: Exercise seems to affect circulating proteins, clinical characteristics, and muscle strength in FM. This study contributes to better understanding of systemic protein changes in FM compared with CON and how resistance exercise affects such changes.

Background: It is known that chronic pain makes it difficult to lose weight, but it is unknown whether obese patients (body mass index ≥30 kg/m²) who experience significant pain relief after interdisciplinary multimodal pain rehabilitation (IMMPR) lose weight.

Objective: This study investigated whether obese patients with chronic pain lost weight after completing IMMPR in specialist pain units. The association of pain relief and weight change over time was also examined.

Methods: Data from obese patients included in the Swedish Quality Registry for Pain Rehabilitation for specialized pain units were used (N=224), including baseline and 12-month follow-up after IMMPR from 2016 to 2018. Patients reported body weight and height, pain aspects (eg, pain intensity), physical activity behaviours, psychological distress, and health-related quality of life (HRQoL). A reduction of at least 5% of initial weight indicates clinically significant weight loss. Patients were classified into three groups based on the pain relief levels after IMMPR: pain relief of clinical significance (30% or more reduction of pain intensity); pain relief without clinical significance (less than 30% reduction of pain intensity); and no pain relief. Linear mixed regression models were used to examine the weight changes among the groups with different pain relief levels.

Results: A significant reduction of pain intensity was found after IMMPR (p < 0.01, effect size Cohen's d = 0.34). A similar proportion of patients in the three groups with different pain relief levels had clinically significant weight loss (20.2%~24.3%, p = 0.47). Significant improvements were reported regarding physical activity behaviour, psychological distress, and HRQoL, but weight change was not associated with changes of pain intensity.

Conclusion: About one-fifth of obese patients achieved significant weight reduction after IMMPR. Obese patients need a tailored pain rehabilitation program incorporating a targeted approach for weight management.

Chronic pain-related sickness absence is an enormous socioeconomic burden globally. Optimized interventions are reliant on a lucid understanding of the distribution of social insurance benefits and their predictors. This register-based observational study analyzed data for a 7-year period from a population-based sample of 44,241 chronic pain patients eligible for interdisciplinary treatment (IDT) at specialist clinics. Sequence analysis was used to describe the sickness absence over the complete period and to separate the patients into subgroups based on their social insurance benefits over the final 2 years. The predictive performance of features from various domains was then explored with machine learning-based modeling in a nested cross-validation procedure. Our results showed that patients on sickness absence increased from 17% 5 years before to 48% at the time of the IDT assessment, and then decreased to 38% at the end of follow-up. Patients were divided into 3 classes characterized by low sickness absence, sick leave, and disability pension, with eight predictors of class membership being identified. Sickness absence history was the strongest predictor of future sickness absence, while other predictors included a 2008 policy, age, confidence in recovery, and geographical location. Information on these features could guide personalized intervention in the specialized healthcare. PERSPECTIVE: This study describes sickness absence in patients who visited a Swedish pain specialist interdisciplinary treatment clinic during the period 2005 to 2016. Predictors of future sickness absence are also identified that should be considered when adapting IDT programs to the patient's needs.

The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia (n = 29) and matched healthy controls (n = 21). Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.