Effectiveness of Pain Neurophysiology Education on Musculoskeletal Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: To estimate the effectiveness and safety of Pain Neurophysiology Education (PNE) on pain, disability, and psychological distress at post-intervention and long-term (closest to twelve months after initiating the intervention) in musculoskeletal pain (MSKP). METHODS: Randomized Controlled Trials (RCT) were identified in six engines, reference lists, ClinicalTrials.gov, and by contacting key researches. Risk of bias was assessed using Cochrane Collaboration Risk of Bias Tool 2.0. Meta-analyses, using Restricted Maximum Likelihood Method, were conducted to estimate standardized mean differences (SMD) and overall quality of evidence was evaluated according to GRADE. RESULTS: In total, 18 RCTs (n = 1,585) were included. There was small to moderate effects of PNE on pain at post-intervention and long-term: SMD = -0.32 (95% confidence interval [CI]: -.58; -.05) and SMD = -0.40 (95% CI: -.78; -.03), respectively. On disability, PNE had a small effect at post-intervention: SMD = -0.17 (95% CI: -.34; -.01) but was insignificant at long-term: SMD = -0.27 (95% CI: -.59; .06). Likewise, there was a small to moderate effect on psychological distress at post-intervention: SMD = -0.36 (95% CI: -.67; -.06) but was insignificant at long-term: SMD = -0.37 (95% CI: -.75; .01). Quality of evidence was low across all outcomes. Additional analyses showed significant effects of PNE, corresponding to moderate effects, on pain and psychological distress at both time points in chronic MSKP. CONCLUSIONS: Overall quality of evidence was low, supporting PNE being safe and having small to moderate effects on pain at both time points, and on disability as well as psychological distress at post-intervention.

Cryoneurolysis for the management of chronic pain in patients with knee osteoarthritis; a double-blinded randomized controlled sham trial.

OBJECTIVE: Pain is the principal symptom in knee osteoarthritis (OA). Current non-operative treatment options have only moderate effects and often patients experience persistent pain or side-effects. Novel advances in the field of cryoneurolysis applies low temperatures to disrupt nerve signaling at the painful area, providing pain relief. The primary aim of this randomized controlled trial (RCT) is to investigate if cryoneurolysis is superior to sham at decreasing pain intensity 2 weeks after the intervention in patients with knee OA. Secondary aims are to explore effects on pain, quality of life and functional performance over 24 months. METHODS: This two-arm, parallel-group RCT, approved by the Regional Ethics Committee, will randomly allocate patients (n = 94) to a cryoneurolysis intervention group + standardized education and exercise (CRYO) or a sham group + standardized education and exercise (SHAM) (1:1 ratio). Both groups will be assessed at baseline, 2 weeks post intervention, post education and exercise and at 6, 12 and 24 months after cryoneurolysis. The primary outcome is the NRS knee pain intensity score assessed 2 weeks post the intervention. Secondary outcome measures include functional performance (chair-stand test, 40 m walk, stair test and maximum voluntary contraction of the knee), patient reported outcomes (quality of life (EQ5D), Knee and osteoarthritis outcome scores (KOOS), among others), use of analgesics, and adverse events over 24 months. IMPACT STATEMENT: Cryoneurolysis could potentially provide an effective, safe and non-pharmacological therapeutic option to treat pain in OA patients. The potential benefits include increased functional capacity and quality of life as a result of significant pain relief and improved benefits of physical exercise. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03774121 , registered 3 March 2018, http://www.clinicaltrials.gov.

Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose-Response Relationships.

OBJECTIVE: This study explores dose-response relationships when treating fibromyalgia with low-dose naltrexone. DESIGN: A single-blinded clinical trial was carried out using the "up-and-down" method. SUBJECTS: Subjects included women with a diagnosis of fibromyalgia aged 18-60 years who had been referred to treatment at a public pain clinic at a Danish university hospital. METHODS: The test doses were in the range 0.75-6 mg, and the dosing interval was 0.75 mg. The method was sequential and allowed predicting the dose effective in 50% (ED50) and 95% (ED95) of the subjects when the dose had shifted direction 10 times, and six pairs of "up-and-down" data were available. RESULTS: A total of 27 subjects were included in the study; two subjects were withdrawn. After inclusion of 25 evaluable subjects, the dose estimates were calculated as 3.88 mg for ED50 and 5.40 mg for ED95. As a secondary outcome, the effects on 10 common fibromyalgia symptoms were evaluated. A high interindividual variation was observed both in the symptom presentation at baseline and in which symptoms were reduced by low-dose naltrexone. CONCLUSIONS: This study is the first to explore dose-response relationships in the treatment of fibromyalgia with low-dose naltrexone. Future placebo-controlled randomized clinical trials are needed, and according to our findings, 4.5 mg, which has previously been used, seems to be a relevant test dose. We recommend that future studies include additional nonpain fibromyalgia symptoms as outcome measures.

Systemic Exercise-Induced Hypoalgesia Following Isometric Exercise Reduces Conditioned Pain Modulation.

Objective: Physically active individuals show greater conditioned pain modulation (CPM) compared with less active individuals. Understanding the effects of acute exercise on CPM may allow for a more targeted use of exercise in the management of pain. This study investigated the effects of acute isometric exercise on CPM. In addition, the between-session and within-session reliability of CPM was investigated. Design: Experimental, randomized crossover study. Setting: Laboratory at Marquette University. Subjects: Thirty healthy adults (19.3±1.5 years, 15 males). Methods: Subjects underwent CPM testing before and after isometric exercise (knee extension, 30% maximum voluntary contraction for three minutes) and quiet rest in two separate experimental sessions. Pressure pain thresholds (PPTs) at the quadriceps and upper trapezius muscles were assessed before, during, and after ice water immersions. Results: PPTs increased during ice water immersion (i.e., CPM), and quadriceps PPT increased after exercise (P < 0.05). CPM decreased similarly following exercise and quiet rest (P > 0.05). CPM within-session reliability was fair to good (intraclass correlation coefficient [ICC] = 0.43-0.70), and the between-session reliability was poor (ICC = 0.20-0.35). Due to the variability in the systemic exercise-induced hypoalgesia (EIH) response, participants were divided into systemic EIH responders (N = 9) and nonresponders (N = 21). EIH responders experienced attenuated CPM following exercise (P = 0.03), whereas the nonresponders showed no significant change (P > 0.05). Conclusions: Isometric exercise decreased CPM in individuals who reported systemic EIH, suggesting activation of shared mechanisms between CPM and systemic EIH responses. These results may improve the understanding of increased pain after exercise in patients with chronic pain and potentially attenuated CPM.

Exercise-Induced Hypoalgesia After Isometric Wall Squat Exercise: A Test-Retest Reliabilty Study.

Background: Isometric exercises decrease pressure pain sensitivity in exercising and nonexercising muscles known as exercise-induced hypoalgesia (EIH). No studies have assessed the test-retest reliability of EIH after isometric exercise. This study investigated the EIH on pressure pain thresholds (PPTs) after an isometric wall squat exercise. The relative and absolute test-retest reliability of the PPT as a test stimulus and the EIH response in exercising and nonexercising muscles were calculated. Methods: In two identical sessions, PPTs of the thigh and shoulder were assessed before and after three minutes of quiet rest and three minutes of wall squat exercise, respectively, in 35 healthy subjects. The relative test-retest reliability of PPT and EIH was determined using analysis of variance models, Person's r, and intraclass correlations (ICCs). The absolute test-retest reliability of EIH was determined based on PPT standard error of measurements and Cohen's kappa for agreement between sessions. Results: Squat increased PPTs of exercising and nonexercising muscles by 16.8% ± 16.9% and 6.7% ± 12.9%, respectively (P < 0.001), with no significant differences between sessions. PPTs within and between sessions showed moderately strong correlations (r ≥ 0.74) and excellent (ICC ≥ 0.84) within-session (rest) and between-session test-retest reliability. EIH responses of exercising and nonexercising muscles showed no systematic errors between sessions; however, the relative test-retest reliability was low (ICCs = 0.03-0.43), and agreement in EIH responders and nonresponders between sessions was not significant (κ < 0.13, P > 0.43). Conclusions: A wall squat exercise increased PPTs compared with quiet rest; however, the relative and absolute reliability of the EIH response was poor. Future research is warranted to investigate the reliability of EIH in clinical pain populations.

Assessing Endogenous Pain Inhibition: Test-Retest Reliability of Exercise-Induced Hypoalgesia in Local and Remote Body Parts After Aerobic Cycling.

OBJECTIVE: Acute exercise can trigger a hypoalgesic response (exercise-induced hypoalgesia [EIH]) in healthy subjects. Despite promising application possibilities of EIH in the clinical context, its reliability has not been sufficiently examined. This study therefore investigated the between-session and within-subject test-retest reliability of EIH at local and remote body parts after aerobic cycling at a heart rate-controlled intensity. METHODS: Thirty healthy adults (15 women) performed 15 minutes of aerobic cycling in two sessions. Pressure pain thresholds (PPTs) were assessed at the leg (local), the back (semilocal), and the hand (remote) before, immediately after, and 15 minutes after exercise. Intraclass correlation coefficients (ICCs) were calculated for absolute and percent changes in PPT from baseline to immediately postexercise, and between-session agreement of EIH responders was examined. RESULTS: PPTs significantly increased at the leg during both sessions (all P < 0.001) and at the back during session 2 (P < 0.001), indicating EIH. Fair between-session reliability was shown for absolute changes at the leg (ICC = 0.54) and the back (ICC = 0.40), whereas the reliability of percent changes was poor (ICC < 0.33). Reliability at the hand was poor for both absolute and percent changes (ICC < 0.33). Agreement in EIH responders was not significant for EIH at the leg or the back (all P > 0.05). CONCLUSIONS: Our results suggest fair test-retest reliability of EIH after aerobic cycling for local and semilocal body parts, but only in men, demonstrating the need for more standardized methodological approaches to improve EIH as a clinical parameter.

Hypoalgesia after bicycling at lactate threshold is reliable between sessions.

PURPOSE: Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate threshold compared with quiet rest, and investigate between-session reliability of EIH. METHODS: Thirty-four healthy subjects completed three sessions with 7 days in-between. In session 1, the lactate threshold was determined via blood samples (finger-tip pinprick, > 2 mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3, all subjects performed (1) 15 min quiet-rest, and (2) 15 min bicycling (work-rate corresponding to the lactate threshold) in the two identical sessions. PPTs at the quadriceps and trapezius muscles were assessed before and after both conditions. Reliability was assessed by intraclass correlations (ICCs). RESULTS: Bicycling increased quadriceps PPT compared with quiet-rest in both sessions [mean difference: 45 kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in trapezius PPT was not significant after exercise. The EIH responses demonstrated fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius: ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between sessions was significant (quadriceps: κ = 0.46 and trapezius: κ = 0.43, P < 0.05). CONCLUSIONS: In conclusion, bicycling at the lactate threshold increased PPT at the exercising muscle with fair reliability of the local EIH response. The results have implications for future EIH studies in subjects with and without pain and for clinicians who design exercise programs for pain relief.

Pain-Related Acceptance as a Mediator in the Fear Avoidance Model of Chronic Pain: A Preliminary Study.

Objective: The fear avoidance model has served as a popular, heuristic model in explaining the transition from acute to chronic pain. In addition, the significance of pain-related acceptance in chronic pain development and adjustment is underlined in a vast number of empirical studies. The objective of the current preliminary study was to investigate pain-related acceptance as a mediator within the key cognitive relationships proposed by the fear avoidance model of chronic pain. Materials and Methods. In a cross-sectional design, bodily pain, pain catastrophizing, fear avoidance beliefs, and pain-related acceptance were assessed by questionnaires in 125 chronic pain patients in a Danish multidisciplinary pain center. Mediation analyses were performed to test the effect of pain-related acceptance on bodily pain, pain catastrophizing, and fear avoidance beliefs. Results: Medium-sized correlations were found between all outcomes. Mediation analyses revealed that pain-related acceptance was a significant mediator between 1) bodily pain and pain catastrophizing and 2) pain catastrophizing and fear avoidance beliefs after controlling for bodily pain. Furthermore, pain-related acceptance accounted for a large proportion in both associations (82.2% and 56.1%). Conclusions: The results suggest that pain-related acceptance is a prominent psychological mechanism within the key cognitive associations of the fear avoidance model, which predicts a certain path of cognitive, emotional, and behavioral factors in the development and maintenance of chronic pain. This proposes pain-related acceptance to be an important mechanism that possibly counteracts the negative reactions of pain catastrophizing and fear avoidance beliefs. These findings should be investigated further and could potentially be an important place to intervene clinically in order to counteract the development and/or maintenance of chronic pain.

Test-Retest Reliabilty of Exercise-Induced Hypoalgesia After Aerobic Exercise.

Objective: Exercise increases pressure pain thresholds (PPTs) in exercising and nonexercising muscles, known as exercise-induced hypoalgesia (EIH). No studies have investigated the test-retest reliability of change in PPTs after aerobic exercise. Primary objectives were to compare the effect on PPTs after an incremental bicycling exercise compared with quiet rest and to investigate the relative and absolute test-retest reliability of the test stimulus (PPT) and the absolute and relative EIH response in exercising and nonexercising muscles. Setting: Laboratory. Methods: In two sessions, PPTs in the quadriceps and trapezius muscles were assessed before and after 15 minutes of quiet rest and 15 minutes of bicycling in 34 healthy subjects. Habitual physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Results: Bicycling increased PPTs in exercising and nonexercising muscles in both sessions (P < 0.05). The magnitude of the EIH response in the exercising muscle was, however, larger in the second compared with the first session (P < 0.015). PPTs showed excellent (intraclass correlation [ICC] ≥ 0.84) within-session and between-session test-retest reliability. The EIH response in exercising and nonexercising muscles demonstrated fair (ICC = 0.45) between-session relative test-retest reliability, but agreement in EIH responders between sessions was not significant (quadriceps: κ = 0.24, P = 0.15; trapezius: κ = 0.01, P = 0.97). Positive correlations between the IPAQ score and PPTs were found (quadriceps: r = 0.44, P = 0.009; trapezius: r = 0.31, P = 0.07) before exercise. No significant association was found between IPAQ and EIH. Conclusions: Incremental bicycling exercise increased PPTs with fair relative and absolute reliability of the EIH response. These data might have an impact on future studies investigating EIH and for clinicians designing exercise programs for pain relief.

Isometric Back Exercise Has Different Effect on Pressure Pain Thresholds in Healthy Men and Women.

Objective: Isometric exercises produce an acute decrease in the pain sensitivity, known as exercise-induced hypoalgesia (EIH). Existing EIH paradigms use exercises at the extremities with more pronounced EIH at local compared to remote body sites, indicating local inhibition in addition to central inhibitory mechanisms. So far the results on EIH in patients with low back pain (LBP) are equivocal and no studies have investigated an EIH paradigm targeting the lower back in order to assess EIH in patients with LBP. Thus, the aim of this pilot study was to assess pressure pain sensitivity at local and remote assessment sites, before and after an isometric back exercise in healthy women and men. Methods: In a pre-posttest design, pressure pain thresholds (PPT) were assessed at the lower back, biceps femoris muscle, and hand in 29 healthy subjects (17 women) before and after 120 seconds of the isometric Biering-Soerensen back extension test. Results: After exercise, PPT increased significantly at the hand in women, but not in men ( P = 0.027). Moreover, PPT at the leg increased independently of sex ( P < 0.004). The increase in PPT at the lower back after exercise approached significance ( P = 0.07). Conclusions: The results of this pilot study indicate that isometric back exercise produces local and remote hypoalgesia. Remote EIH was only demonstrated in women, supporting the influence of sex in the hypoalgesic response after exercise. The effect of isometric back exercise on pain sensitivity in patients with low back pain should be investigated in future studies.

A 13-Weeks Mindfulness Based Pain Management Program Improves Psychological Distress in Patients with Chronic Pain Compared with Waiting List Controls.

BACKGROUND: Eradication of pain is seldom an option in chronic pain management. Hence, mindfulness meditation has become popular in pain management. OBJECTIVE: This pilot study compared the effect of a 13-weeks cognitive behavioural therapy program with integrated mindfulness meditation (CBTm) in patients with chronic non-malignant pain with a control condition. It was hypothesised that the CBTm program would reduce pain intensity and psychological distress compared to the control condition and that level of mindfulness and acceptance both would be associated with the reduction in pain intensity and psychological distress. METHODS: A case-control design was used and data were collected from a convenience sample of 70 patients with chronic non-malignant pain. Fifty patients were consecutively recruited to the CBTm intervention and 20 patients matched waiting list controls. Assessments of clinical pain and psychological distress were performed in both groups at baseline and after 13 weeks. RESULTS: The CBTm program reduced depression, anxiety and pain-catastrophizing compared with the control group. Increased level of mindfulness and acceptance were associated with change in psychological distress with the exception of depression, which was only associated with change in level of mindfulness. Surprisingly, changes in level of mindfulness did not correlate with changes in acceptance. CONCLUSIONS: The results indicate that different mechanisms are targeted with cognitive behavioural therapy and mindfulness. The finding that changes in level of mindfulness did not correlate with changes in acceptance may indicate that acceptance is not a strict prerequisite for coping with pain related distress.

Aerobic exercise and cold pressor test induce hypoalgesia in active and inactive men and women.

BACKGROUND: Physical inactivity is a risk factor for chronic pain. Several mechanisms play a role in pain chronification including impairment of pain inhibition. OBJECTIVE: This study compared the efficiency of pain inhibitory systems between physical active and inactive healthy subjects. It was hypothesized that active subjects had more efficient pain inhibition compared with inactive subjects. DESIGN: A randomized, crossover study with 2 days of data collection. METHODS: Fifty-six (28 females) subjects participated in this study. Subjects were subgrouped into active (n = 30) and inactive (n = 26). Conditioned pain modulation (CPM) was assessed by cold pressor testing. Exercise-induced hypoalgesia (EIH) was assessed after 15 minutes bicycling at a heart rate corresponding to 75% VO2max. A control session of 15 minutes quiet rest was also included. Pressure pain thresholds (PPTs) were recorded at the dominant arm and leg before, immediately after, and 15 minutes after conditioning and exercise as well as before and after rest. PPTs were also recorded during conditioning. RESULTS: At baseline, PPTs in inactive men were increased compared with inactive women (P < 0.003). During cold pressor test and after exercise, PPTs increased to the same degree in active and inactive subjects, and the CPM and EIH responses were correlated (P < 0.05). The CPM response immediately after cold pressor test was maintained in women but not in men. CONCLUSIONS: Cold pressor stimulation and aerobic exercise caused comparable multisegmental increases in PPT in active and inactive men and women. The CPM and EIH responses were correlated, but they have different temporal manifestation of hypoalgesia.

Prevalence of neuropathic pain according to the IASP grading system in patients with chronic non-malignant pain.

OBJECTIVE: The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. SETTING: A Multidisciplinary Pain Center. SUBJECTS: One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. METHODS: Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. RESULTS: According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. CONCLUSIONS: According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire.

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).

Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Low-dose naltrexone is used to treat fibromyalgia despite minimal evidence for its efficacy. This trial aimed to investigate whether 12-week treatment with 6 mg low-dose naltrexone was superior to placebo for reducing pain in women with fibromyalgia. METHODS: We did a single-centre, randomised, double-blind, placebo-controlled trial in Denmark. We enrolled women aged 18-64 years who were diagnosed with fibromyalgia. Participants were randomly assigned 1:1 to receive low-dose naltrexone (6 mg) or an identical-appearing placebo, using a computerised algorithm with no stratifications applied. Participants, investigators, outcome assessors, and statistical analysts were all masked to treatment allocation. The primary outcome was change in pain intensity on an 11-point numeric rating scale from baseline to week 12, in the intention-to-treat population. Safety was assessed in participants in the intention-to-treat population who received at least one dose of their allocated intervention. This trial was registered with ClincalTrials.gov (NCT04270877) and EudraCT (2019-000702-30). FINDINGS: We screened 158 participants for eligibility from Jan 6, 2021, to Dec 27, 2022, and 99 patients were randomly assigned to low-dose naltrexone (n=49) or placebo (n=50). The mean age was 50·6 years (SD 8·8), one (1%) of 99 participants was Arctic Asian and 98 (99%) were White. No participants were lost to follow-up. The mean change in pain intensity was -1·3 points (95% CI -1·7 to -0·8) in the low-dose naltrexone group and -0·9 (-1·4 to -0·5) in the placebo group, corresponding to a between-group difference of -0·34 (-0·95 to 0·27; p=0·27, Cohen's d 0·23). Discontinuations due to adverse events were four (8%) of 49 in the low-dose naltrexone group and three (6%) of 50 in the placebo group. 41 (84%) of 49 patients in the low-dose naltrexone group had an adverse event versus 43 (86%) of 50 in the placebo group. One serious adverse event occurred in the placebo group and no deaths occurred. INTERPRETATION: This study did not show that treatment with low-dose naltrexone was superior to placebo in relieving pain. Our results indicate that low-dose naltrexone might improve memory problems associated with fibromyalgia, and we suggest that future trials investigate this further. FUNDING: The Danish Rheumatism Association, Odense University Hospital, Danielsen's Foundation, and the Oak Foundation.

Changes in pain, daily occupations, lifestyle, and health following an occupational therapy lifestyle intervention: a secondary analysis from a feasibility study in patients with chronic high-impact pain.

OBJECTIVES: This study explored changes in pain-related parameters, occupational function, occupational balance, lifestyle factors, and self-perceived health status in adults with chronic high-impact pain participating in an occupational therapy lifestyle intervention. METHODS: This one-group longitudinal feasibility study was performed in three continuous feasibility rounds. The occupational therapists-led intervention targeted meaningful occupations, regular physical activity, and a healthy diet. The intervention contained individual and group sessions and was added to the standard multidisciplinary chronic pain treatment. Outpatients (n=40, 85 % females, 46.6 ± 10.9 years old) participated in the study between April 2019 and December 2021. The analysis includes data for 31 participants. Analysis of pre-post changes assessed after each feasibility round were performed for the outcomes: pain intensity, pain sensitivity and pain modulation (pressure pain threshold and tolerance, temporal summation of pain and conditioned pain modulation), pain self-efficacy, pain catastrophizing, motor and process skills, occupational balance, daily wake-time movement, daily walking steps, body mass index, waist circumference, blood pressure, and self-perceived health status. RESULTS: Improvements in motor skills (assessment of motor and process skills score=0.20 (1.37; 1.57), 95 % CI 0.01; 0.38) and temporal summation of pain (-1.19 (2.86; -1.67), 95 % CI -2.16; -0.22), but a decrease in pain tolerance (-7.110 (54.42; 47.32), 95 % CI -13.99; -0.22) were observed. Correlation analysis suggested moderate-to-very strong statistically significant relationships in several outcomes related to pain, health, pain coping, occupational balance, occupational functioning, body anthropometrics, and pain sensitivity. CONCLUSIONS: This study suggested that the lifestyle intervention would benefit motor skills while effects on other outcomes were unclear in adults with chronic pain. To confirm the findings, a randomized trial evaluating effectiveness is needed. Ethical committee number: SJ-307 Reg. Clinicaltrials.gov: NCT03903900.

Physical activity should be the primary intervention for individuals living with chronic pain A position paper from the European Pain Federation (EFIC) 'On the Move' Task Force.

BACKGROUND: There is clear evidence demonstrating the benefits of physical activity (PA) on pain and overall health, however, PA is challenging for many individuals living with chronic pain. Even non-exercise specialists can (cost) effectively promote PA, but many health professionals report a number of barriers in providing guidance on PA, suggesting that it is not consistently promoted. This expert position paper summarizes the evidence and provides five recommendations for health professionals to assess, advise and support individuals living with any chronic pain condition with a long life expectancy in adopting and sustaining physically active lifestyles. METHODS: This position paper was prepared by the 'On The Move' Task Force of the European Pain Federation EFIC. Final recommendations were endorsed by the European Pain Forum, Pain Alliance Europe and the Executive Board of EFIC. RESULTS: We recommend that all health professionals (1) Take a history of the persons' PA levels, and put PA on the agenda, (2) Advise that PA is important and safe for individuals living with chronic pain, (3) Deliver a brief PA intervention and support individuals living with chronic pain in becoming physically active, (4) Discuss acceptable levels of PA-related soreness and pain and (5) Provide ongoing support in staying physically active. SIGNIFICANCE: Physical activity is safe and offers several advantages, including general health benefits, low risk of side effects, low cost and not requiring access to healthcare. Adoption of these recommendations can improve the quality of care and life of individuals living with chronic pain and reduce their overall health risks.

Less is more: reliability and measurement error for three versions of the Tampa Scale of Kinesiophobia (TSK-11, TSK-13, and TSK-17) in patients with high-impact chronic pain.

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 (ICC2,1), and measurement error in terms of standard error of measurement (SEMagreement) and SDC95% were calculated. RESULTS: All three versions showed good test-retest reliability with ICC2,1-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.

Interpretation of the Patient Health Questionnaire 9 in High-Impact Chronic Pain: Do We Measure Depressive Symptoms the Way We Think?

OBJECTIVES: Depression is prevalent among patients with chronic pain and may impact pain management. An accurate assessment is, however, complicated by overlapping symptoms. This study investigated how patients with high-impact chronic pain interpreted and responded to the Patient Health Questionnaire 9 (PHQ-9) to identify problematic items and causes hereof. MATERIALS AND METHODS: Cognitive interviews using the Three-Step Test-Interview procedure were conducted during the completion of the PHQ-9 in 33 patients with high-impact chronic pain referred to interdisciplinary treatment. Responses were analyzed using 4 coding categories: (1) "congruent" (response consistent with intention); (2) "incongruent" (response not consistent intention); (3) "ambiguous" (response both congruent and incongruent or insufficient to evaluate congruency); and (4) "confused" (response with confused or misunderstood statements). Next, the content of responses to problematic items was analyzed to identify causes for noncongruency, and encountered response difficulties were identified across all items. RESULTS: Three items (items 2, 6, and 9) performed as intended (>97% congruent responses), while 7 items (items 1, 3, 4, 5, 7, 8, and 10) were identified as problematic (<50% congruent responses). Problematic items had 1 or more issues: Responses were based on (1) pain-related issues or (2) other (non-pain) factors unrelated to depression, or item structure caused response difficulties due to wordings, reversion, or having 2 questions in 1. DISCUSSION: Problematic items limit the construct validity of the PHQ-9, leaving an increased risk of inflated depression scores in high-impact chronic pain. Identified problems should guide future revisions to enhance validity and screening accuracy for the benefit of both research and clinical practice.

The Effect of Virtual Reality on Cold Pain Sensitivity in Patients with Fibromyalgia and Pain-Free Individuals: A Randomized Crossover Study.

Introduction: Fibromyalgia is a complex pain syndrome with high personal and societal costs, with only few effective tools for treatment. Virtual reality (VR) may be an efficient pain management tool although the effectiveness in fibromyalgia patients is unclear. Objective: This randomized crossover study set out to 1) investigate the effect of VR on cold pain threshold, -tolerance, and -intensity in fibromyalgia patients and in pain-free individuals and 2) explore the potential relationships between the effect of VR and pain catastrophizing. Materials and Methods: Twenty-two female fibromyalgia patients and 22 sex- and age-matched pain-free individuals participated in two conditions (one with VR and one without VR) with foot immersion in 1°C-2°C cold water. The order of conditions was randomized and counterbalanced for each group. Conditions were separated by 20 minutes. Cold pain threshold, -tolerance, and -intensity were assessed during the conditions. Pain catastrophizing was assessed using the Pain Catastrophizing Scale. Results: VR induced moderate to large increases in cold pain threshold and pain tolerance compared with the control condition for both the fibromyalgia group and pain-free individuals (P < 0.03). Pain intensity was reduced after VR only in pain-free individuals (P < 0.003). Pain catastrophizing was not related to VR effect on pain threshold, -tolerance, or -intensity for any group. Conclusion: VR had a significant effect on pain threshold and tolerance in fibromyalgia patients and pain-free individuals, which supports its ability to distract from pain. Future studies exploring the VR's potential as part of clinical pain management alone or in combination with other treatments are warranted. ClinicalTrials.gov (NCT04294914).