Masayuki Koga, Shintaro Fujii, Yuki Nishi, Koki Koyama, Akihisa Maeda, Kanako Fujikawa, Shu Morioka
Background
Pain, fear, and motor function are interrelated. This study aimed to clarify their causal relationships by examining longitudinal changes from the preoperative to the acute postoperative period after total knee arthroplasty (TKA).
Methods
This exploratory prospective observational study included 27 inpatients (mean age, 74.1 years [SD = 9.9]; 40 knees). Pain, fear and motor function were assessed preoperatively and 1 and 2 weeks postoperatively. At each time point, rest pain, motion pain, fear of motion, and kinematic parameters of knee movement (velocity, angle, surplus null and spectral entropy) were measured. The cross-lagged panel model was used to estimate causal relationships.
Results
Longitudinal analysis revealed that reduced movement at 1 week predicted greater rest pain at 2 weeks, and higher rest pain at 1 week predicted more excessive movement irregularity at 2 weeks. Models including preoperative factors did not meet the goodness-of-fit criteria and were therefore excluded.
Conclusions
Pain and motor function predicted each other through distinct factors and pathways during the acute postoperative recovery period after TKA. These interactions may contribute to persistent pain and functional limitations, highlighting the need for targeted early interventions.
Significance
Understanding the temporal relationships between acute postoperative pain and knee kinematics may provide insights into the mechanisms underlying prolonged recovery.
Significance Statement
Excessive behavioural avoidance in the acute postoperative period may be involved in prolonged pain and motor dysfunction after total knee arthroplasty. In this study, longitudinal analysis of pain, fear, and motor impairment (behaviour) was conducted using a cross lagged panel model. Decreased range of motion in the acute phase predicted delayed pain recovery, whereas pain intensity predicted awkward movement. These results may indicate specific problems that should be addressed in the early postoperative period.
{"title":"Temporal Relationship Among Pain, Fear, and Motor Function After Total Knee Arthroplasty: An Exploratory Study","authors":"Masayuki Koga, Shintaro Fujii, Yuki Nishi, Koki Koyama, Akihisa Maeda, Kanako Fujikawa, Shu Morioka","doi":"10.1002/ejp.70210","DOIUrl":"10.1002/ejp.70210","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pain, fear, and motor function are interrelated. This study aimed to clarify their causal relationships by examining longitudinal changes from the preoperative to the acute postoperative period after total knee arthroplasty (TKA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This exploratory prospective observational study included 27 inpatients (mean age, 74.1 years [SD = 9.9]; 40 knees). Pain, fear and motor function were assessed preoperatively and 1 and 2 weeks postoperatively. At each time point, rest pain, motion pain, fear of motion, and kinematic parameters of knee movement (velocity, angle, surplus null and spectral entropy) were measured. The cross-lagged panel model was used to estimate causal relationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Longitudinal analysis revealed that reduced movement at 1 week predicted greater rest pain at 2 weeks, and higher rest pain at 1 week predicted more excessive movement irregularity at 2 weeks. Models including preoperative factors did not meet the goodness-of-fit criteria and were therefore excluded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pain and motor function predicted each other through distinct factors and pathways during the acute postoperative recovery period after TKA. These interactions may contribute to persistent pain and functional limitations, highlighting the need for targeted early interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Understanding the temporal relationships between acute postoperative pain and knee kinematics may provide insights into the mechanisms underlying prolonged recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Excessive behavioural avoidance in the acute postoperative period may be involved in prolonged pain and motor dysfunction after total knee arthroplasty. In this study, longitudinal analysis of pain, fear, and motor impairment (behaviour) was conducted using a cross lagged panel model. Decreased range of motion in the acute phase predicted delayed pain recovery, whereas pain intensity predicted awkward movement. These results may indicate specific problems that should be addressed in the early postoperative period.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiya Yu, Li Gou, Jielei Huang, Lisheng Wang, Baoyu Chen, Yuan Kang, Lin Yang
Background
Frozen shoulder (FS) has long been considered a localised musculoskeletal disorder, yet FS often involves widespread pain, suggesting central sensory dysregulation. While pressure pain threshold (PPT) assesses mechanical sensitivity, electrical measures such as current perception threshold (CPT) and electrical pain threshold (EPT) may capture various sensory alterations but are rarely applied in FS.
Objective
To map somatosensory alterations in unilateral FS by comparing PPT, CPT, and EPT across multiple regions with matched healthy controls (HC).
Methods
37 unilateral FS participants and 35 matched HCs underwent PPT, CPT, and EPT measurements at lateral deltoid (LD), medial forearm (MF), cervical spine (CS), and lumbar spine (LS). Bilateral LD and MF were tested in FS participants. Between-group and regional differences were analysed using linear mixed models, and correlations with pain intensity were examined.
Results
FS participants exhibited significantly reduced PPT across all sites (d = 1.27–4.55) and increased CPT and EPT at affected LD and CS regions (d = 2.89–4.92). Electrical thresholds were higher over CS than LS in the FS group, whereas the opposite pattern appeared in the HC group. EPT correlated with PPT (ρ = 0.54), and both were negatively associated with pain intensity (ρ = −0.72 and −0.69, p < 0.001).
Conclusions
FS demonstrates mechanical hyperalgesia and electrical hypoesthesia, indicating central neuroplastic changes beyond the affected shoulder.
Significance Statement
This study integrates electrical and mechanical sensory testing, revealing multimodal evidence of central sensitization in FS and offering novel quantitative markers to guide individualised pain assessment and rehabilitation.
{"title":"Frozen Shoulder Is More Than Local Pain: Widespread Sensory Hyperalgesia or Hypoesthesia?","authors":"Shiya Yu, Li Gou, Jielei Huang, Lisheng Wang, Baoyu Chen, Yuan Kang, Lin Yang","doi":"10.1002/ejp.70215","DOIUrl":"10.1002/ejp.70215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Frozen shoulder (FS) has long been considered a localised musculoskeletal disorder, yet FS often involves widespread pain, suggesting central sensory dysregulation. While pressure pain threshold (PPT) assesses mechanical sensitivity, electrical measures such as current perception threshold (CPT) and electrical pain threshold (EPT) may capture various sensory alterations but are rarely applied in FS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To map somatosensory alterations in unilateral FS by comparing PPT, CPT, and EPT across multiple regions with matched healthy controls (HC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>37 unilateral FS participants and 35 matched HCs underwent PPT, CPT, and EPT measurements at lateral deltoid (LD), medial forearm (MF), cervical spine (CS), and lumbar spine (LS). Bilateral LD and MF were tested in FS participants. Between-group and regional differences were analysed using linear mixed models, and correlations with pain intensity were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>FS participants exhibited significantly reduced PPT across all sites (<i>d</i> = 1.27–4.55) and increased CPT and EPT at affected LD and CS regions (<i>d</i> = 2.89–4.92). Electrical thresholds were higher over CS than LS in the FS group, whereas the opposite pattern appeared in the HC group. EPT correlated with PPT (<i>ρ</i> = 0.54), and both were negatively associated with pain intensity (<i>ρ</i> = −0.72 and −0.69, <i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FS demonstrates mechanical hyperalgesia and electrical hypoesthesia, indicating central neuroplastic changes beyond the affected shoulder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This study integrates electrical and mechanical sensory testing, revealing multimodal evidence of central sensitization in FS and offering novel quantitative markers to guide individualised pain assessment and rehabilitation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trail Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: ChiCTR2400086393</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12809871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jens Frøjk Axel Dixen, Malene Ravn, Thorvaldur Skuli Palsson, Kristian Kjær-Staal Petersen, Morten Hoegh
Background
Aerobic exercise leads to transient hypoalgesia, but little is known about these effects over extended periods. This study aimed to investigate exercise-induced hypoalgesia (EIH) responses in healthy individuals during long-distance running on a treadmill.
Methods
Thirty healthy participants (18–50 years) completed a 15 km treadmill run. Pain sensitivity was assessed using pain pressure threshold (PPT) before and during the run. Additionally, cuff-PPT (cPPT), cuff-pressure pain tolerance threshold (cPTT), temporal summation of pain (TSP) and conditioned pain modulation (CPM) were assessed with pressure cuff algometry before and during the run. Data were analysed using repeated measures ANOVA. Exploratory subgroups, based on changes in PPT, were identified using latent growth mixture models, and logistic regression was used to predict subgroup membership.
Results
No significant changes were observed over time for PPT, PTT, cPPT or CPM at the group level. TSP decreased significantly after 10 and 15 km (p ≤ 0.004) when compared to baseline. Exploratory analysis identified two distinct subgroups: ‘increasing PPT’ and ‘decreasing PPT’. Subgroup membership was predicted using baseline CPM and EIH (p < 0.045).
Conclusion
This study found no significant changes in PPT, cPPT, or CPM following aerobic exercise. A significant change was observed in TSP. CPM and EIH predicted changes in PPT during the 15 km run (increasing vs. decreasing) in an explorative analysis. Further research should test if baseline tests can predict pro- or anti-nociceptive responses to long-distance running.
Significance Statement
These findings highlight the importance of individual variability in endogenous pain modulation during endurance exercise. The lack of group-level effects underscores the need to move beyond average responses and consider subgroups when studying exercise-induced hypoalgesia. Identifying distinct modulatory profiles may offer insight into personalized exercise interventions and reveal stable traits related to pain regulation. This has potential clinical implications for tailoring exercise as a pain management strategy and for identifying individuals at risk of negative or absent hypoalgesic responses.
{"title":"The Development of the Pain Threshold During a Long-Distance Run","authors":"Jens Frøjk Axel Dixen, Malene Ravn, Thorvaldur Skuli Palsson, Kristian Kjær-Staal Petersen, Morten Hoegh","doi":"10.1002/ejp.70199","DOIUrl":"10.1002/ejp.70199","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Aerobic exercise leads to transient hypoalgesia, but little is known about these effects over extended periods. This study aimed to investigate exercise-induced hypoalgesia (EIH) responses in healthy individuals during long-distance running on a treadmill.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty healthy participants (18–50 years) completed a 15 km treadmill run. Pain sensitivity was assessed using pain pressure threshold (PPT) before and during the run. Additionally, cuff-PPT (cPPT), cuff-pressure pain tolerance threshold (cPTT), temporal summation of pain (TSP) and conditioned pain modulation (CPM) were assessed with pressure cuff algometry before and during the run. Data were analysed using repeated measures ANOVA. Exploratory subgroups, based on changes in PPT, were identified using latent growth mixture models, and logistic regression was used to predict subgroup membership.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant changes were observed over time for PPT, PTT, cPPT or CPM at the group level. TSP decreased significantly after 10 and 15 km (<i>p</i> ≤ 0.004) when compared to baseline. Exploratory analysis identified two distinct subgroups: ‘increasing PPT’ and ‘decreasing PPT’. Subgroup membership was predicted using baseline CPM and EIH (<i>p</i> < 0.045).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found no significant changes in PPT, cPPT, or CPM following aerobic exercise. A significant change was observed in TSP. CPM and EIH predicted changes in PPT during the 15 km run (increasing vs. decreasing) in an explorative analysis. Further research should test if baseline tests can predict pro- or anti-nociceptive responses to long-distance running.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>These findings highlight the importance of individual variability in endogenous pain modulation during endurance exercise. The lack of group-level effects underscores the need to move beyond average responses and consider subgroups when studying exercise-induced hypoalgesia. Identifying distinct modulatory profiles may offer insight into personalized exercise interventions and reveal stable traits related to pain regulation. This has potential clinical implications for tailoring exercise as a pain management strategy and for identifying individuals at risk of negative or absent hypoalgesic responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michelle Hamani, Daniel Ciampi de Andrade, Lisandra Stein Bernardes
Background
The perception and assessment of foetal pain remains a contentious topic due to challenges in evaluating and detecting non-verbal behaviours. While it is widely accepted that newborns experience pain, measured through validated behavioural scales, debate persists regarding the onset of pain perception during intrauterine development.
Methods
We reviewed the available literature to prepare a position paper, aiming to argue that foetuses in their 2nd to 3rd trimester may in fact feel pain and exhibit different shades of consciousness.
Results
Emerging evidence challenges the binary view of consciousness (e.g., present/absent), suggesting that foetuses may possess some aspects of consciousness such as levels of awareness and responsiveness, both necessary and sufficient for pain perception. Advances in 4D ultrasound technology have enabled the assessment of foetal facial expressions indicative of pain, leading to the development of specialised foetal pain behaviour scales. Targeted hand movements, MEG and EEG provide further evidence of goal-directedness and action planning, while engagement in different learning paradigms (ex. habituation) provides evidence for preliminary memory and higher-order cognition.
Conclusions
Research into foetal pain will contribute not only to better clinical care but will enrich the fields of bioethics and neurodevelopmental neuroscience.
Significance
This position paper provides an overview of the current research concerning foetal pain behaviour and awareness. Reflections on foetal pain may bring insights not only to the pain field, but also to neuroethics, clinical and neurodevelopmental sciences.
{"title":"Human Foetuses Experience Pain: A Position Paper","authors":"Michelle Hamani, Daniel Ciampi de Andrade, Lisandra Stein Bernardes","doi":"10.1002/ejp.70206","DOIUrl":"10.1002/ejp.70206","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The perception and assessment of foetal pain remains a contentious topic due to challenges in evaluating and detecting non-verbal behaviours. While it is widely accepted that newborns experience pain, measured through validated behavioural scales, debate persists regarding the onset of pain perception during intrauterine development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed the available literature to prepare a position paper, aiming to argue that foetuses in their 2nd to 3rd trimester may in fact feel pain and exhibit different shades of consciousness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Emerging evidence challenges the binary view of consciousness (e.g., present/absent), suggesting that foetuses may possess some aspects of consciousness such as levels of awareness and responsiveness, both necessary and sufficient for pain perception. Advances in 4D ultrasound technology have enabled the assessment of foetal facial expressions indicative of pain, leading to the development of specialised foetal pain behaviour scales. Targeted hand movements, MEG and EEG provide further evidence of goal-directedness and action planning, while engagement in different learning paradigms (ex. habituation) provides evidence for preliminary memory and higher-order cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Research into foetal pain will contribute not only to better clinical care but will enrich the fields of bioethics and neurodevelopmental neuroscience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This position paper provides an overview of the current research concerning foetal pain behaviour and awareness. Reflections on foetal pain may bring insights not only to the pain field, but also to neuroethics, clinical and neurodevelopmental sciences.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Small-scale care providers often encounter challenges in demonstrating the effectiveness of treatments through randomised controlled trials (RCTs) because of the high costs and organisational demands of RCTs. The current study examines the feasibility of evaluating a multidisciplinary treatment for chronic low back pain using a waiting list as a control group.
Material and Methods
Of 344 chronic pain patients referred to a Dutch outpatient rehabilitation clinic, 123 received treatment, while 88 were on a waiting list. The main effect parameters were pain (visual analogue scale), daily limitations (Quebec Back Pain Disability Scale), and fear of motion (Tampa Scale for Kinesiophobia). Data were collected at the beginning of treatment, after 8 weeks, and after 3 months (follow-up), or after another 8 weeks for waitlist patients receiving treatment after the waiting list period.
Results
The intervention group showed significant persistent improvement in relation to pain (54.1 ± 22.0 to 34.8 ± 23.6), daily limitations (45.1 ± 15.3 to 32.9 ± 15.4), and fear of motion (36.5 ± 8.5 to 30.0 ± 7.3). Subsequently, 51 subjects on the waiting list received treatment, with results similar to those of the initial intervention group. Dysfunctional pain coping strategies diminished during therapy.
Discussion
Multidisciplinary rehabilitation was shown to be more effective than being placed on a waiting list, even when participants were receiving other treatments. Small-scale, high-quality effect studies using a waiting list control group may have scientific potential.
Significance
RCT's are considered the gold standard in effect studies; however, due to financial, organisational, and ethical concerns, performing RCT's can be difficult for small-sized care settings that provide multidisciplinary rehabilitation for chronic back pain. As a result, these treatment options often do not receive sufficient scientific or clinical attention. This study demonstrates that alternative methodologically transparent effect studies using a “waiting list” control can be conducted in small-scale clinical settings with limited means.
{"title":"Effectiveness of Multidisciplinary Rehabilitation in Chronic Low Back Pain: A Pragmatic Study With a Waiting List Control Group","authors":"J. P. van Wingerden, T. van Opstal","doi":"10.1002/ejp.70209","DOIUrl":"10.1002/ejp.70209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Small-scale care providers often encounter challenges in demonstrating the effectiveness of treatments through randomised controlled trials (RCTs) because of the high costs and organisational demands of RCTs. The current study examines the feasibility of evaluating a multidisciplinary treatment for chronic low back pain using a waiting list as a control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>Of 344 chronic pain patients referred to a Dutch outpatient rehabilitation clinic, 123 received treatment, while 88 were on a waiting list. The main effect parameters were pain (visual analogue scale), daily limitations (Quebec Back Pain Disability Scale), and fear of motion (Tampa Scale for Kinesiophobia). Data were collected at the beginning of treatment, after 8 weeks, and after 3 months (follow-up), or after another 8 weeks for waitlist patients receiving treatment after the waiting list period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The intervention group showed significant persistent improvement in relation to pain (54.1 ± 22.0 to 34.8 ± 23.6), daily limitations (45.1 ± 15.3 to 32.9 ± 15.4), and fear of motion (36.5 ± 8.5 to 30.0 ± 7.3). Subsequently, 51 subjects on the waiting list received treatment, with results similar to those of the initial intervention group. Dysfunctional pain coping strategies diminished during therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Multidisciplinary rehabilitation was shown to be more effective than being placed on a waiting list, even when participants were receiving other treatments. Small-scale, high-quality effect studies using a waiting list control group may have scientific potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>RCT's are considered the gold standard in effect studies; however, due to financial, organisational, and ethical concerns, performing RCT's can be difficult for small-sized care settings that provide multidisciplinary rehabilitation for chronic back pain. As a result, these treatment options often do not receive sufficient scientific or clinical attention. This study demonstrates that alternative methodologically transparent effect studies using a “waiting list” control can be conducted in small-scale clinical settings with limited means.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manon Sendel, Lena Ehmke, Andreas Dunst, Jan Vollert, Henrike Bruckmüller, Sandra Brügge, Stefanie Rehm, Janne Gierthmühlen, Dilara Kersebaum, Ingolf Cascorbi, Ralf Baron, Julia Forstenpointner
Background
Topical high-dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non-interventional exploratory study was to improve prediction of treatment response to high-dose capsaicin by including quantifiable parameters and standardised questionnaires.
Methods
Forty-eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient-reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser-speckle-contrast-analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO-synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).
Results
Patient-reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.
Conclusion
A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high-dose capsaicin treatment and provide promising targets for future investigation.
Significance Statement
This exploratory study identifies promising predictors for analgesic response to high-concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve-fibre assessments and genetic polymorphisms.
{"title":"Response to High-Dose Topical Capsaicin in Neuropathic Pain: Absence of Deep Pain as a Predictor of Analgesic Effect","authors":"Manon Sendel, Lena Ehmke, Andreas Dunst, Jan Vollert, Henrike Bruckmüller, Sandra Brügge, Stefanie Rehm, Janne Gierthmühlen, Dilara Kersebaum, Ingolf Cascorbi, Ralf Baron, Julia Forstenpointner","doi":"10.1002/ejp.70200","DOIUrl":"10.1002/ejp.70200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Topical high-dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non-interventional exploratory study was to improve prediction of treatment response to high-dose capsaicin by including quantifiable parameters and standardised questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient-reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser-speckle-contrast-analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO-synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient-reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high-dose capsaicin treatment and provide promising targets for future investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This exploratory study identifies promising predictors for analgesic response to high-concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve-fibre assessments and genetic polymorphisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuukka Korpela, Jaro Karppinen, Petteri Oura, Markus Paananen, Arnold Y. L. Wong, Ilona Merikanto, Eveliina Heikkala
Background
Musculoskeletal (MSK) pain and insomnia are interrelated and individually linked to reduced health-related quality of life (HRQoL). This study aimed to enlighten the association of concurrent disabling MSK pain and insomnia with HRQoL among middle-aged individuals.
Methods
Members of the Northern Finland Birth Cohort 1966 were surveyed at age 46 years (analytic sample N = 4 130, 56.7% women). Validated Athens insomnia scale was used to determine insomnia status and HRQoL was assessed with the 15D (15-dimensional) questionnaire. Associations between different combinations of disabling MSK pain and insomnia (concurrent, isolated, absent) with HRQoL were analysed using general linear regression, adjusting for sex, smoking, educational level, physical activity and coexisting diseases. Fifteen HRQoL dimensions were also analysed separately.
Results
The prevalence of concurrent disabling MSK pain and insomnia was 14.3%, while 50.8% reported neither condition. Adjusted 15D mean score of participants with concurrent disabling MSK pain and insomnia was significantly lower (beta [β] coefficient: −0.068 [95% CI −0.073 to −0.062]) compared to those without. Concurrent conditions were associated with lower HRQoL than isolated insomnia and isolated disabling MSK pain (β coefficients: −0.032 [95% CI −0.039 to −0.024] and −0.042 [95% CI −0.050 to −0.034], respectively). Fourteen of 15 HRQoL dimensions were the lowest among participants with concurrent conditions.
Conclusions
This study shows that every seventh of the study population has disabling MSK pain and insomnia concurrently and they are more strongly associated with lower HRQoL compared to isolated or absent conditions. The negative effects of comorbid conditions on HRQoL are reflected across multiple dimensions.
Significance Statement
Musculoskeletal pain and insomnia together exert a compounded negative effect on health-related quality of life, highlighting the need for integrated management strategies. Treating pain alone may not be enough and routine sleep assessment could be a critical point.
背景：肌肉骨骼（MSK）疼痛和失眠相互关联，并与健康相关生活质量（HRQoL）降低单独相关。本研究旨在揭示中年人同时致残的MSK疼痛和失眠与HRQoL的关系。方法：对1966年芬兰北部出生队列46岁的成员进行调查（分析样本N = 4130, 56.7%为女性）。采用经验证的雅典失眠症量表评估失眠状况，采用15D（15维）问卷评估HRQoL。使用一般线性回归分析致残性MSK疼痛和失眠（并发、孤立、不存在）的不同组合与HRQoL之间的关系，调整性别、吸烟、教育水平、体育活动和共存疾病。15个HRQoL维度也分别进行了分析。结果：并发致残MSK疼痛和失眠的患病率为14.3%，而50.8%的人没有出现这种情况。与不伴有致残性MSK疼痛和失眠的受试者相比，伴有致残性MSK疼痛和失眠的校正后15D平均评分显著降低（β [β]系数：-0.068 [95% CI -0.073至-0.062]）。与孤立性失眠和孤立性致残性MSK疼痛相比，并发条件与较低的HRQoL相关（β系数分别为-0.032 [95% CI -0.039至-0.024]和-0.042 [95% CI -0.050至-0.034]）。15个HRQoL维度中有14个在并发疾病的参与者中最低。结论：本研究表明，七分之一的研究人群同时患有致残性MSK疼痛和失眠，与孤立或无症状相比，它们与较低的HRQoL相关性更强。合并症对HRQoL的负面影响反映在多个维度上。意义说明：肌肉骨骼疼痛和失眠共同对健康相关的生活质量产生复合的负面影响，突出了综合管理策略的必要性。仅仅治疗疼痛可能是不够的，常规的睡眠评估可能是一个关键点。
{"title":"Musculoskeletal Pain, Insomnia and Health-Related Quality of Life: Associations in the Middle-Aged General Population","authors":"Tuukka Korpela, Jaro Karppinen, Petteri Oura, Markus Paananen, Arnold Y. L. Wong, Ilona Merikanto, Eveliina Heikkala","doi":"10.1002/ejp.70197","DOIUrl":"10.1002/ejp.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Musculoskeletal (MSK) pain and insomnia are interrelated and individually linked to reduced health-related quality of life (HRQoL). This study aimed to enlighten the association of concurrent disabling MSK pain and insomnia with HRQoL among middle-aged individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Members of the Northern Finland Birth Cohort 1966 were surveyed at age 46 years (analytic sample <i>N</i> = 4 130, 56.7% women). Validated Athens insomnia scale was used to determine insomnia status and HRQoL was assessed with the 15D (15-dimensional) questionnaire. Associations between different combinations of disabling MSK pain and insomnia (concurrent, isolated, absent) with HRQoL were analysed using general linear regression, adjusting for sex, smoking, educational level, physical activity and coexisting diseases. Fifteen HRQoL dimensions were also analysed separately.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of concurrent disabling MSK pain and insomnia was 14.3%, while 50.8% reported neither condition. Adjusted 15D mean score of participants with concurrent disabling MSK pain and insomnia was significantly lower (beta [<i>β</i>] coefficient: −0.068 [95% CI −0.073 to −0.062]) compared to those without. Concurrent conditions were associated with lower HRQoL than isolated insomnia and isolated disabling MSK pain (<i>β</i> coefficients: −0.032 [95% CI −0.039 to −0.024] and −0.042 [95% CI −0.050 to −0.034], respectively). Fourteen of 15 HRQoL dimensions were the lowest among participants with concurrent conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study shows that every seventh of the study population has disabling MSK pain and insomnia concurrently and they are more strongly associated with lower HRQoL compared to isolated or absent conditions. The negative effects of comorbid conditions on HRQoL are reflected across multiple dimensions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Musculoskeletal pain and insomnia together exert a compounded negative effect on health-related quality of life, highlighting the need for integrated management strategies. Treating pain alone may not be enough and routine sleep assessment could be a critical point.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12767138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Mema, Julia A. Glombiewski, Christopher Milde, Ulrike Basten, Julia Karbach, Tanja Könen, Tanja Lischetzke, Lea Schemer
Background
Emotion regulation (ER) is considered a transdiagnostic mechanism underlying chronic pain (CP) and depression in theoretical models such as the Örebro framework. Yet most work has focused on between-person differences rather than within-person dynamics.
Methods
This study examined whether individuals with CP show lower ER success than those without CP (NCP), whether ER or pain regulation (PR) success varies with pain experience and negative emotions at within- and between-person levels, and whether pain duration exacerbates these effects via reduced self-efficacy. Participants included a CP group (n = 176) and an NCP group (n = 161) who completed baseline assessments and a 2-week ambulatory assessment (AA) with five daily surveys.
Results
The CP group had significantly lower ER success than the NCP group (moderate effect: d = −0.48). Within the CP group, ER success decreased with higher-than-usual pain experience (large within-person effect: d = −0.72) and higher overall pain experience (moderate between-person effect: d = −0.55). Similarly, higher-than-usual negative emotions (moderate within-person effect: d = −0.43) and higher overall negative emotions (small between-person effect: d = −0.36) were linked to lower PR success. Pain duration did not moderate the relationship between pain experience and ER success.
Conclusion
Findings align with the Örebro model, suggesting that pain flare-ups and negative mood strain the ER system and contribute to ER difficulties in CP, though long-term processes were not captured by pain duration or self-efficacy.
Significance Statement
By zooming in on within-person dynamics, this study adds to growing research on ER difficulties as a transdiagnostic factor underlying chronic pain and co-occurring emotional problems. Clinically, our findings highlight the potential of just-in-time interventions integrated with ER-focused pain management, offering support at moments of greatest need.
{"title":"Emotion Regulation in Chronic Pain Is Impaired When Pain Is High: Results From a Large Ambulatory Assessment Study","authors":"Christina Mema, Julia A. Glombiewski, Christopher Milde, Ulrike Basten, Julia Karbach, Tanja Könen, Tanja Lischetzke, Lea Schemer","doi":"10.1002/ejp.70204","DOIUrl":"10.1002/ejp.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emotion regulation (ER) is considered a transdiagnostic mechanism underlying chronic pain (CP) and depression in theoretical models such as the Örebro framework. Yet most work has focused on between-person differences rather than within-person dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study examined whether individuals with CP show lower ER success than those without CP (NCP), whether ER or pain regulation (PR) success varies with pain experience and negative emotions at within- and between-person levels, and whether pain duration exacerbates these effects via reduced self-efficacy. Participants included a CP group (<i>n</i> = 176) and an NCP group (<i>n</i> = 161) who completed baseline assessments and a 2-week ambulatory assessment (AA) with five daily surveys.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CP group had significantly lower ER success than the NCP group (moderate effect: <i>d</i> = −0.48). Within the CP group, ER success decreased with higher-than-usual pain experience (large within-person effect: <i>d</i> = −0.72) and higher overall pain experience (moderate between-person effect: <i>d</i> = −0.55). Similarly, higher-than-usual negative emotions (moderate within-person effect: <i>d</i> = −0.43) and higher overall negative emotions (small between-person effect: <i>d</i> = −0.36) were linked to lower PR success. Pain duration did not moderate the relationship between pain experience and ER success.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Findings align with the Örebro model, suggesting that pain flare-ups and negative mood strain the ER system and contribute to ER difficulties in CP, though long-term processes were not captured by pain duration or self-efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>By zooming in on within-person dynamics, this study adds to growing research on ER difficulties as a transdiagnostic factor underlying chronic pain and co-occurring emotional problems. Clinically, our findings highlight the potential of just-in-time interventions integrated with ER-focused pain management, offering support at moments of greatest need.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Eck, Stephan Bigalke, Martin Schmelz, Daniela Constanze Rosenberger, Bruno Pradier, Frank Rutsch, Claudia Sommer, Frank Birklein, Daniel Segelcke, Esther Pogatzki-Zahn
Background
Peripheral neuropathies (PNP) cause a wide range of symptoms of which pruritus and pain are a major burden to patients. Clarifying their mechanisms will facilitate the adequate symptom management. In contrast to neuropathic pain, neuropathic pruritus has long been understudied. We investigate inhibitory pruritus mechanisms in patients with PNP.
Methods
A total of 39 participants (median age: 57 years [27–81], 25♀/14♂), including 16 patients with PNP and pruritus (PNPPRU) and 8 with PNP but without pruritus (PNPNO-PRU), and 15 controls, were enrolled and phenotyped using dynamic and static quantitative sensory testing, determination of intradermal nerve fibre density, and conditioned pain (CPM) and itch (CIM) modulation. For CIM, an electrically induced itch test stimulus (TS) was applied with an individual itch intensity of > 30 NRS (0–100). A cold-water bath (contralateral side) served as the conditioning stimulus (CS). Itch, pain intensity and the desire to scratch upon TS were rated before, during and after the CS was applied.
Results
Using our novel CIM protocol, well-controlled and stable itch was electrically induced in controls and in both PNP groups, regardless of whether or not pruritus was a symptom. Concomitant painful cold stimuli reduced electrically induced itch in all three groups to a similar degree. However, PNPPRU patients had significantly shorter itch inhibition (CIM effects) compared to controls and PNPNO-PRU, whereas CPM effects were not different between groups.
Conclusions
The results show reduced endogenous itch inhibition in patients with chronic itch, which represents a possible mechanism of chronic pruritus in PNP.
Significance Statement
Reduced itch inhibition is associated with the symptom of chronic pruritus in PNP patients, suggesting that reduced descending itch inhibition may facilitate chronic itch in peripheral neuropathy.
{"title":"Reduced Descending Itch Inhibition in Peripheral Neuropathy Patients With Chronic Pruritus","authors":"Jonas Eck, Stephan Bigalke, Martin Schmelz, Daniela Constanze Rosenberger, Bruno Pradier, Frank Rutsch, Claudia Sommer, Frank Birklein, Daniel Segelcke, Esther Pogatzki-Zahn","doi":"10.1002/ejp.70190","DOIUrl":"10.1002/ejp.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Peripheral neuropathies (PNP) cause a wide range of symptoms of which pruritus and pain are a major burden to patients. Clarifying their mechanisms will facilitate the adequate symptom management. In contrast to neuropathic pain, neuropathic pruritus has long been understudied. We investigate inhibitory pruritus mechanisms in patients with PNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 39 participants (median age: 57 years [27–81], 25♀/14♂), including 16 patients with PNP and pruritus (PNP<sub>PRU</sub>) and 8 with PNP but without pruritus (PNP<sub>NO-PRU</sub>), and 15 controls, were enrolled and phenotyped using dynamic and static quantitative sensory testing, determination of intradermal nerve fibre density, and conditioned pain (CPM) and itch (CIM) modulation. For CIM, an electrically induced itch test stimulus (TS) was applied with an individual itch intensity of > 30 NRS (0–100). A cold-water bath (contralateral side) served as the conditioning stimulus (CS). Itch, pain intensity and the desire to scratch upon TS were rated before, during and after the CS was applied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using our novel CIM protocol, well-controlled and stable itch was electrically induced in controls and in both PNP groups, regardless of whether or not pruritus was a symptom. Concomitant painful cold stimuli reduced electrically induced itch in all three groups to a similar degree. However, PNP<sub>PRU</sub> patients had significantly shorter itch inhibition (CIM effects) compared to controls and PNP<sub>NO-PRU</sub>, whereas CPM effects were not different between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results show reduced endogenous itch inhibition in patients with chronic itch, which represents a possible mechanism of chronic pruritus in PNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Reduced itch inhibition is associated with the symptom of chronic pruritus in PNP patients, suggesting that reduced descending itch inhibition may facilitate chronic itch in peripheral neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Víctor Riquelme-Aguado, María Elena González-Álvarez, Silvia Di-Bonaventura, Leonardo Rodríguez-Lagos, Alazne Zabarte del Campo, Francisco Gómez-Esquer, Gema Díaz-Gil, Antonio Gil-Crujera
<div> <section> <h3> Introduction</h3> <p>Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response.</p> </section> <section> <h3> Objectives</h3> <p>To examine associations between selected genetic polymorphisms and psychological variables in women with FM.</p> </section> <section> <h3> Methods</h3> <p>A cross-sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables—anxiety, depression and catastrophising—were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped (<i>COMT</i> rs4680, <i>DRD3</i> rs6280, <i>OPRM1</i> rs1799971, <i>BDNF</i> rs6265, <i>MAOA</i> rs1137070, <i>FKBP5</i> rs1360780, <i>IL6</i> rs1800796, <i>TNF</i> rs1800629, <i>IL10</i> rs1800896, <i>IFITM3</i> rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal–Wallis with Tukey or Mann–Whitney post hoc tests.</p> </section> <section> <h3> Results</h3> <p>Pain intensity correlated with depression (<i>r</i> = 0.476, <i>p</i> < 0.001), catastrophising (<i>r</i> = 0.414, <i>p</i> < 0.001), and anxiety (<i>r</i> = 0.314, <i>p</i> = 0.009). Catastrophising was related to depression (<i>r</i> = 0.615, <i>p</i> < 0.001), anxiety (<i>r</i> = 0.453, <i>p</i> < 0.001), and kinesiophobia (<i>r</i> = 0.445, <i>p</i> < 0.001). <i>BDNF</i> rs6265 was associated with catastrophising (<i>p</i> = 0.044), <i>OPRM1</i> rs1799971 with anxiety (<i>p</i> = 0.030), and <i>MAOA</i> rs1137070 with depression (<i>p</i> = 0.020).</p> </section> <section> <h3> Conclusions</h3> <p>Psychological variables in FM are interrelated and linked to pain perception. <i>BDNF</i>, <i>OPRM1</i> and <i>MAOA</i> polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM.</p> </section> <section> <h3> Significance Statement</h3> <p>Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psy
{"title":"Associations Between Genetic Polymorphisms and Psychological Variables in Women With Fibromyalgia: A Cross-Sectional Study","authors":"Víctor Riquelme-Aguado, María Elena González-Álvarez, Silvia Di-Bonaventura, Leonardo Rodríguez-Lagos, Alazne Zabarte del Campo, Francisco Gómez-Esquer, Gema Díaz-Gil, Antonio Gil-Crujera","doi":"10.1002/ejp.70201","DOIUrl":"10.1002/ejp.70201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To examine associations between selected genetic polymorphisms and psychological variables in women with FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables—anxiety, depression and catastrophising—were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped (<i>COMT</i> rs4680, <i>DRD3</i> rs6280, <i>OPRM1</i> rs1799971, <i>BDNF</i> rs6265, <i>MAOA</i> rs1137070, <i>FKBP5</i> rs1360780, <i>IL6</i> rs1800796, <i>TNF</i> rs1800629, <i>IL10</i> rs1800896, <i>IFITM3</i> rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal–Wallis with Tukey or Mann–Whitney post hoc tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pain intensity correlated with depression (<i>r</i> = 0.476, <i>p</i> < 0.001), catastrophising (<i>r</i> = 0.414, <i>p</i> < 0.001), and anxiety (<i>r</i> = 0.314, <i>p</i> = 0.009). Catastrophising was related to depression (<i>r</i> = 0.615, <i>p</i> < 0.001), anxiety (<i>r</i> = 0.453, <i>p</i> < 0.001), and kinesiophobia (<i>r</i> = 0.445, <i>p</i> < 0.001). <i>BDNF</i> rs6265 was associated with catastrophising (<i>p</i> = 0.044), <i>OPRM1</i> rs1799971 with anxiety (<i>p</i> = 0.030), and <i>MAOA</i> rs1137070 with depression (<i>p</i> = 0.020).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Psychological variables in FM are interrelated and linked to pain perception. <i>BDNF</i>, <i>OPRM1</i> and <i>MAOA</i> polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psy","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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