Reliability and measurement error of exercise-induced hypoalgesia in pain-free adults and adults with musculoskeletal pain: A systematic review.

OBJECTIVES: We systematically reviewed the reliability and measurement error of exercise-induced hypoalgesia (EIH) in pain-free adults and in adults with musculoskeletal (MSK) pain. METHODS: We searched EMBASE, PUBMED, SCOPUS, CINAHL, and PSYCINFO from inception to November 2021 (updated in February 2024). In addition, manual searches of the grey literature were conducted in March 2022, September 2023, and February 2024. The inclusion criteria were as follows: adults - pain-free and with MSK pain - a single bout of exercise (any type) combined with experimental pre-post pain tests, and assessment of the reliability and/or measurement error of EIH. Two independent reviewers selected the studies, assessed their Risk of Bias (RoB) with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) RoB tool, and graded the individual results (COSMIN modified Grading of Recommendations Assessment, Development, and Evaluation). RESULTS: We included five studies involving pain-free individuals (n = 168), which were deemed to have an overall "doubtful" RoB. No study including adults with MSK pain was found. The following ranges of parameters of reliability and measurement error of EIH were reported: intraclass correlation coefficients: 0-0.61; kappa: 0.01-0.46; standard error of measurement: 30.1-105 kPa and 10.4-21%; smallest detectable changes: 83.54-291.1 kPa and 28.83-58.21%. CONCLUSIONS: We concluded, with a very low level of certainty, that the reliability and measurement error of EIH is, in pain-free adults, respectively, "insufficient" and "indeterminate." Future studies should focus on people with MSK pain and could consider using tailored exercises, other test modalities than pressure pain threshold, rater/assessor blinding, and strict control of the sources of variations (e.g., participants' expectations).

Conditioned pain modulation (CPM) paradigm type affects its sensitivity as a biomarker of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, disease impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, we did not observe any correlation between CPM measures and clinical symptoms. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.

Paradox pain sensitivity using cuff pressure or algometer testing in patients with hemophilia.

INTRODUCTION: Pain is a common comorbidity in patients with hemophilia (PwH) due to hemophilic arthropathy. This study aims to explore pain sensitivity in PwH methodologically investigating in cuff pressure testing compared to algometer testing. METHODS: 37 PwH and 35 healthy control subjects (Con) enrolled in this study. Joint health status was assessed. Subjective pain was evaluated using numeric rating scales. Pain sensitivity was measured with pressure algometry and cuff pressure algometry. Pressure pain thresholds of the algometer (PPTa) were measured at knee, ankle joints, and forehead. Subsequently, thresholds of cuff pressure were measured at the left and right lower legs (PPTcuff). In both, lower values represent higher pain sensitivity. RESULTS: PwH exerted a worse joint health status than Con. Pain sensitivity was higher in PwH compared to Con as PPTa of the knee and ankle joints were lower in PwH. No difference was observed in PPTa at the forehead. Contrastingly, lower pain sensitivity was detected in PwH by higher PPTcuff values compared to Con in both legs. CONCLUSION: While PPTa of the knee and ankle joints are lower in PwH, PPTcuff are higher in PwH compared to Con. This reveals a paradox situation, highlighting that PwH experience local, joint- and hemophilic arthropathy-related pain, whereas pain sensitivity of non-affected soft tissue structures is lower. The reasons explaining the PPTcuff results remain elusive but might be explained by coping strategies counteracting chronic joint pain, resulting in lower sensitivity at non-affected structures.

Investigating mortality salience as a potential causal influence and moderator of responses to laboratory pain.

Background: Because pain can have profound ramifications for quality of life and daily functioning, understanding nuances in the interplay of psychosocial experiences with pain perception is vital for effective pain management. In separate lines of research, pain resilience and mortality salience have emerged as potentially important psychological correlates of reduced pain severity and increased tolerance of pain. However, to date, there has been a paucity of research examining potentially interactive effects of these factors on pain perception. To address this gap, the present experiment investigated mortality salience as a causal influence on tolerance of laboratory pain and a moderator of associations between pain resilience and pain tolerance within a Chinese sample. Methods: Participants were healthy young Chinese adults (86 women, 84 men) who first completed a brief initial cold pressor test (CPT) followed by measures of demographics and pain resilience. Subsequently, participants randomly assigned to a mortality salience (MS) condition completed two open-ended essay questions in which they wrote about their death as well as a death anxiety scale while those randomly assigned to a control condition completed analogous tasks about watching television. Finally, all participants engaged in a delay task and a second CPT designed to measure post-manipulation pain tolerance and subjective pain intensity levels. Results: MS condition cohorts showed greater pain tolerance than controls on the post-manipulation CPT, though pain intensity levels did not differ between groups. Moderator analyses indicated that the relationship between the behavior perseverance facet of pain resilience and pain tolerance was significantly stronger among MS condition participants than controls. Conclusions: This experiment is the first to document potential causal effects of MS on pain tolerance and Ms as a moderator of the association between self-reported behavior perseverance and behavioral pain tolerance. Findings provide foundations for extensions within clinical pain samples.

Exercise induced hypoalgesia during different intensities of a dynamic resistance exercise: A randomized controlled trial.

INTRODUCTION: Exercise produces an immediate lessening of pain sensitivity (Exercise-Induced Hypoalgesia (EIH)) in healthy individuals at local and distant sites, possibly through a shared mechanism with conditioned pain modulation (CPM). Dynamic resistance exercise is a recommended type of exercise to reduce pain, yet limited research has examined the effects of intensity on EIH during this type of exercise. Therefore, the primary purpose of this study is to compare changes in PPT at a local and distant site during a leg extension exercise at a high intensity, a low intensity, or a quiet rest condition. A secondary purpose is to examine if CPM changes after each intervention. The final purpose is to examine if baseline pain sensitivity measures are correlated with response to each intervention. METHODS: In a randomized controlled trial of 60 healthy participants, participants completed baseline pain sensitivity testing (heat pain threshold, temporal summation, a cold pressor test as measure of CPM) and were randomly assigned to complete a knee extension exercise at: 1) high intensity (75% of a 1 Repetition Maximum (RM), 2) low intensity (30% 1RM), or 3) Quiet Rest. PPT was measured between each set at a local (quadriceps) and distant (trapezius) site during the intervention. CPM was then repeated after the intervention. To test the first purpose of the study, a three-way ANOVA examined for time x site x intervention interaction effects. To examine for changes in CPM by group, a mixed-model ANOVA was performed. Finally, a Pearson Correlation examined the association between baseline pain sensitivity and response to each intervention. RESULTS: Time x site x intervention interaction effects were not significant (F(5.3, 150.97) = 0.87, p = 0.51, partial eta2 = 0.03). CPM did not significantly change after the interventions (time x intervention F(1,38) = 0.81, p = 0.37, partial eta2 = 0.02. EIH effects at the quadriceps displayed a significant, positive moderate association with baseline HPT applied over the trapezius (r = 0.61, p<0.01) and TS (r = 0.46, p = 0.04). DISCUSSION: In healthy participants, PPT and CPM did not significantly differ after a leg extension exercise performed at a high intensity, low intensity, or quiet rest condition. It is possible pre-intervention CPM testing with a noxious stimuli may have impaired inhibitory effects frequently observed during exercise but future research would need to examine this hypothesis.

Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial.

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. METHODS/DESIGN: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

COMPARISON THE EFFICACY OF DRY NEEDLING AND ISCHEMIC COMPRESSION METHODS IN MIYOFASCIAL PAIN SYNDROME: A RANDOMIZED TRIAL.

Myofascial pain syndrome (MPS) is the most common in the musculoskeletal disease. Dry needling techniques and ischemic compression are the most common applications. We aimed to compare the efficacy of dry needling and ischemic compression methods on pain, cervical range of motion and disability in myofascial pain syndrome. This is a randomized, controlled study. 98 patients with MPS were randomly assigned into three groups. Group1 received dry needling (n=33), group 2 (n=33) received ischemic compression and group 3 (n=32) received combined with dry needling and ischemic compression inventions. Additionally, all patients were given neck exercise programs including isotonic, isometric, and stretching. The severity of the pain was measured by visual analog scale (VAS). The pressure pain threshold (PPT) and cervical range of motion (ROM) were also recorded. Disability was assessed by the Neck Pain Disability Scale. All assessments were performed before the treatment and one month and three months after the treatment. There were statistically significant improvements in VAS, PPT, cervical ROM, and disability scores after one and three months in all groups compared to pre-treatment results (p<0.05). After three months of follow-up, statistically significant differences were observed in all parameters between the groups (p<0.05) except cervical ROM (p>0.05). Myofascial pain syndrome in patients with ischemic compression and dry needling effective treatment methods are shown separately in our study to be more effective when used together.

Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

Linear and curvilinear association of pain tolerance and social anxiety symptoms among youth with different subgroups of childhood trauma.

BACKGROUND: Social anxiety is a common symptom that occurs after exposure to childhood trauma (CT), and pain tolerance is a protective factor against social anxiety in generic populations with CT. However, few studies have investigated whether and how this association varies across different CT subgroups. Thus, this study aimed to investigate (1) the effects of pain tolerance on social anxiety symptoms among youth with different subgroups of CT; (2) the nonlinear relationship between pain tolerance and social anxiety symptoms among different CT categories. METHODS: In this study, 15,682 college or university students with experiences of CT were identified in a large sample and divided into five CT subgroups. Linear and quadratic regression models were conducted to explore the association between pain tolerance and social anxiety symptoms among youth with different CT subgroups. RESULTS: The results of model revealed a linear relationship between pain tolerance and social anxiety symptoms among youth with most CT subgroups. Notably, an inverted U-shaped curve was found between pain tolerance and social anxiety symptoms in youth with emotional abuse. Social anxiety symptoms increased gradually with pain tolerance scores between 0 and 16, and then sharply decreased when scores reached above 16. LIMITATIONS: Limited by self-report measurements, the results of this study focused only on perceived pain tolerance and ignored behavioral pain tolerance. CONCLUSION: These findings highlight the importance of assessing pain tolerance thresholds in youth with emotional abuse and improving pain tolerance to prevent social anxiety symptoms in youth with different subgroups of CT.

Associations between cognitive test scores and pain tolerance: The Tromsø study.

OBJECTIVES: Previous studies have suggested that experimental pain sensitivity is associated with cognitive function. The aim of this study is to assess this relationship in a large population-based sample. METHODS: We included 5,753 participants (aged 40-84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom information on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12-word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain. RESULTS: In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12-word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90-0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89-0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90-0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94-0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89-0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95-1.00, p = 0.082). CONCLUSION: Lower pain tolerance was associated with poorer performance on cognitive tests.

Concurrent validity of dynamic bedside quantitative sensory testing paradigms in breast cancer survivors with persistent pain.

BACKGROUND: Studies on the concurrent validity of clinically applicable testing protocols for conditioned pain modulation (CPM) and temporal summation of pain (TSP) in breast cancer survivors (BCS) with persistent pain are lacking. OBJECTIVES: This study investigated the concurrent validity of two bedside protocols for CPM and TSP in comparison to a respective reference protocol. The participants' preferences for bedside CPM and TSP protocols were assessed. METHODS: Thirty BCS experiencing persistent pain were included in this study. Each participant underwent a reference test along with two bedside alternatives for assessing both TSP and CPM. For CPM, a cold pressor test (CPT) and blood pressure cuff (BPC) were used as conditioning stimulus. The test stimulus was elicited in parallel by pressure pain threshold after 45 and 90 s of conditioning at the lower limb. The CPM reference test consisted of parallel heat stimuli at the forearms using a two-thermode system. TSP was elicited using a von Frey monofilament (256 mN) and an algometer (98 kPa) at the affected site and opposite lower limb. The TSP reference test consisted of heat stimuli at the affected site and opposite lower limb. Participants' testing preference was examined using a purpose-designed questionnaire. Spearman's rank test examined the correlation between protocols. RESULTS: The two bedside CPM protocols were strongly correlated (r = 0.787-0.939, p < 0.005). A strong correlation was found between the BPC protocol and reference test using the relative effect magnitude (r = 0.541-0.555, p < 0.005). The bedside TSP protocols were moderately correlated with each other only at the lower limb using absolute change scores (r = 0.455, p = 0.012). No significant correlation was found between the bedside and reference TSP protocols. CONCLUSION: The significantly moderate to very strong correlations between the bedside protocols validate their interchangeability. Researchers and clinicians should be able to choose which bedside protocol they utilize; however, participants favored the use of a BPC and algometer for the evaluation of CPM and TSP, respectively.

The Bayliss-Starling Prize Lecture: The developmental physiology of spinal cord and cortical nociceptive circuits.

When do we first experience pain? To address this question, we need to know how the developing nervous system processes potential or real tissue-damaging stimuli in early life. In the newborn, nociception preserves life through reflex avoidance of tissue damage and engagement of parental help. Importantly, nociception also forms the starting point for experiencing and learning about pain and for setting the level of adult pain sensitivity. This review, which arose from the Bayliss-Starling Prize Lecture, focuses on the basic developmental neurophysiology of early nociceptive circuits in the spinal cord, brainstem and cortex that form the building blocks of our first pain experience.

Botulinum toxin-A effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: a randomized double-blind clinical trial.

The antinociceptive effect of BoNT-A have been well documented in animal studies; however, results of few but well-designed randomized placebo-controlled clinical trials about BoNT-A efficacy in masticatory myofascial pain (MFP) are inconsistent. Therefore, the present randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of BoNT-A in patients with refractory MFP. Twenty-eight patients with pain reduction of less than 30% despite conservative treatment and with an average pain intensity of > 50 mm on the visual analogue scale (VAS) participated. Patients were randomly assigned to receive a total of 80 U of BoNT-A or saline solution (SS) injected into the masseter and anterior temporalis muscles. Pain intensity (VAS), quantitative sensory testing (QST), conditioned pain modulation (CPM), and psychosocial status were examined. Follow-up was performed at 1 and 6 months. For repeated-measure comparisons between evaluation times, Friedman test with Bonferroni correction was used for pain and somatosensory variables and the Wilcoxon test for the psychosocial variables. The Mann-Whitney test was used for all comparisons between groups. The BoNT-A group had a significant decrease in pain intensity at follow-ups compared with the SS group (p < 0.001). QST assessment revealed higher pressure pain threshold values in the masseter muscle for BoNT-A group compared to SS (p < 0.03) at all follow-ups. No differences were found for mechanical pain threshold and wind-up ratio values (p > 0.05) in the entire study. The BoNT-A group presented the most efficient CPM effect (p < 0.03) only at the 1 month follow-up in the masseter muscle. There was a significant time effect for BoNT-A in all psychosocial variables (p < 0.05) and a drug effect in the Central Sensitization Inventory (p < 0.01), Pittsburgh Sleep Quality Index (p < 0.004), and Healthy Survey 36 (p < 0.05) at 6 months follow-up. The study demonstrates that a single injection-session of BoNT-A has positive effects on the hall pain spectrum of patients with refractory masticatory myofascial pain.

The effectiveness of a combined exercise and psychological treatment programme on measures of nervous system sensitisation in adults with chronic musculoskeletal pain - a systematic review and meta-analysis.

BACKGROUND: Quantitative sensory testing (QST) offers information regarding underlying mechanisms contributing to chronic pain (CP) in adults with musculoskeletal disorders. This review examined the use of QST measures in adults with CP following participation in a combined exercise and psychological intervention. METHODS: The review was conducted in accordance with the PRISMA guidelines. Five databases were searched from inception to November 2022. All study designs which evaluated the effects of a combined exercise and psychological treatment on measures of nervous system sensitivity in adults with chronic musculoskeletal pain were included. RESULTS: A total of 13 studies met the selection criteria, 10 of which were included in a meta-analysis. Local pressure pain thresholds were the most frequently used measure (n = 12 studies). Meta-analysis revealed statistically significantly improvements in favour of the combined exercise and psychological intervention group, compared to a control group, for local pressure pain threshold measures [SMD = 0.44, 95% CI 0.08-0.81, I2 = 84%], pain intensity scores [SMD=-0.89, 95% CI -1.66- -0.13, I2 = 94%] and the Central Sensitisation Inventory [SMD=-0.69, 95% CI -1.37- -0.02, I2 = 87%]. There were no significant differences found between groups for remote pressure pain thresholds, temporal summation or conditioned pain modulation. CONCLUSIONS: The results suggest that a combined exercise and psychological intervention may lead to greater improvements in local pressure pain threshold, pain intensity and Central Sensitisation Inventory scores when compared to a control intervention in adults with CP, however these findings must be interpreted with caution as a large degree of heterogeneity was present in these results (I2: 84-94%). Further large, longitudinal studies are required using standardised QST measurement procedures and patient reported outcome measures to explore changes in nervous system sensitisation. TRIAL REGISTRATION: This systematic review is registered with PROSPERO, ID Number CRD42022380464.

Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions.

We sought to determine the effects of blood flow restriction (BFR) on exercise-induced hypoalgesia, specifically using low-load (LL) resistance exercise (30% 1RM) protocols that accounted for each individual's local muscular endurance capabilities. Forty-four participants completed four conditions: (1) 70% of maximal BFR repetitions with blood flow restriction (LL+BFR exercise); (2) 70% maximal BFR repetitions without LL+BFR (LL exercise); (3) 70% maximal free flow repetitions (LL+EFFORT exercise); (4) time-matched, non-exercise control (CON). Pressure pain threshold (PPT) was measured before and after exercise. Ischaemic pain threshold and tolerance was assessed only at post. The change in upper body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.15 (0.35) kg/cm2], LL+EFFORT exercise [difference of 0.23 (0.45) kg/cm2], and the CON condition. The change in lower body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.40 (0.55) kg/cm2], LL+EFFORT exercise [difference of 0.36 (0.62) kg/cm2], and the CON condition. Ischaemic pain thresholds and tolerances did not change. Submaximal exercise with BFR resulted in systemic increases in PPT but had no influence on ischaemic pain sensitivity. This effect is likely unique to BFR as we did not see changes in the effort matched free flow condition.

Small fibre pathology, small fibre symptoms and pain in fibromyalgia syndrome.

A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.

Physical activity and pain in people with cancer: a systematic review and meta-analysis.

PURPOSE: Physical activity can provide analgesic benefit but its effect on cancer-related pain is unclear. This review synthesised and appraised the evidence for the effect of physical activity on pain in people living with or beyond cancer. METHODS: A systematic search of Ovid Medline and Embase was performed to identify randomised controlled trials (RCTs), randomised cross-over studies (RXTs), and prospective observational studies that examined physical activity and pain outcomes in adults living with or beyond cancer. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to assess evidence quality. RESULTS: One hundred twenty-one studies (n = 13,806), including 102 RCTs, 6 RXTs, and 13 observational studies, met the criteria for inclusion. Meta-analyses of RCTs identified a decrease in pain intensity (n = 3734; standardised mean difference (SMD) - 0.30; 95% confidence interval (CI) - 0.45, - 0.15) and bodily pain (n = 1170; SMD 0.28; 95% CI 0.01, 0.56) but not pain interference (n = 207; SMD - 0.13, 95% CI - 0.42, 0.15) following physical activity interventions. Individual studies also identified a reduction in pain sensitivity but not analgesic use, although meta-analysis was not possible for these outcomes. High heterogeneity between studies, low certainty in some effect estimates, and possible publication bias meant that evidence quality was graded as very low to low. CONCLUSION: Physical activity may decrease pain in people living with and beyond cancer; however, high heterogeneity limits the ability to generalise this finding to all people with cancer or to specific types of cancer-related pain.

Somatosensory and psychosocial profile of migraine patients: A cross-sectional study.

BACKGROUND: Migraine is a chronic neurological disorder that involves the brain, characterized by a series of abnormal neuronal networks interacting at different levels of the central and peripheral nervous system. Furthermore, it is known that psychosocial features contribute to the exacerbation and chronicity of symptoms. OBJECTIVE: To compare the somatosensory and psychosocial profiles of migraine patients with a control group. METHODS: We conducted a cross-sectional study comparing the somatosensory and psychosocial profiles of patients with migraine and healthy volunteers. A total of 52 women were included. For the somatosensory profile, Mechanical Detection Threshold (MDT), Pressure Pain Threshold (PPT), Temporal Summation (TS), and Conditioned Pain Modulation (CPM) in the trigeminal and extra-trigeminal areas were evaluated. Psychosocial profiles were assessed using questionnaires, the Central Sensitization Inventory, the Generalized Anxiety Disorders, the Pain Catastrophizing Scale, and the Tampa Scale of Kinesiophobia. Mann-Whitney U test was used to compare differences in the profiles between groups. The significance level was set at 5%. RESULTS: Migraine patients showed a loss of somatosensory function in the trigeminal area for MDT (p = 0.019, r = 0.34 and p = 0.011, r = 0.37 for the ophthalmic nerve and masseter muscle respectively), lower PPT in trigeminal and extra-trigeminal areas (p < 0.001, r=>0.60) and less efficient CPM (p < 0.001, r=>0.60). No statistically significant differences were found in the TS (p=>0.05). Statistically significant differences were found in all psychosocial variables (p = <0.001 r=>0.60). CONCLUSION: Migraine patients showed loss of somatosensory function, lower pressure pain threshold, and an inhibitory pro-nociceptive profile with high scores on central sensitization and fear of movement compared to the control group.

Effects of swimming exercise on neuropathic pain in a rat model: role of glutamate.

OBJECTIVE: The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it. METHODS: In the present study 104 male Wistar rats weighing 180-220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography. RESULTS: Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it. IN CONCLUSION: The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission.