Audrey P. Wang, Michael Green, Peter Humburg, G. Lorimer Moseley, James McAuley, Caroline D. Rae
Background
Treatment of chronic pain conditions such as complex regional pain syndrome (CRPS) has been underpinned by the concept of the condition being driven or maintained by disorganisation of the sensory system. Previously reported differences in brain structure and function between individuals with CRPS and healthy controls have supported this concept, although results have been mixed.
Methods
In a cross-sectional study, we examined white matter structure in the brains of people with CRPS and healthy controls (n = 42) using high angular resolution diffusion imaging at 3 Tesla and analysed the data using a fixel-based approach.
Results
We found no significant differences in any diffusion measures between participants with CRPS and controls. Linear regression analyses and equivalence tests demonstrated that fibre density cross-section measures were indistinguishable between the two groups; neither CRPS symptomology nor opioid use could be explained by any white matter structural differences detected by diffusion imaging.
Conclusions
A relatively large sample size and fine-grained methods add confidence to our findings. These results argue against permanent brain changes that prevent recovery in CRPS.
Significance Statement
In one of the largest studies of white matter structure in complex regional pain syndrome, fixel-based high angular resolution diffusion scans showed no significant difference to controls and were statistically equivalent. This indicates that white matter structural change is unlikely to be of clinical significance in CRPS. This points to functional changes underpinning the deficits associated with the condition and highlights improving neural function through movement-based approaches such as graded motor imagery, graded exposure, desensitisation and functional movement rehabilitation approaches.
{"title":"White Matter Structure in Complex Regional Pain Syndrome: A High Angular Resolution and Fixel-Based Study","authors":"Audrey P. Wang, Michael Green, Peter Humburg, G. Lorimer Moseley, James McAuley, Caroline D. Rae","doi":"10.1002/ejp.70202","DOIUrl":"10.1002/ejp.70202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Treatment of chronic pain conditions such as complex regional pain syndrome (CRPS) has been underpinned by the concept of the condition being driven or maintained by disorganisation of the sensory system. Previously reported differences in brain structure and function between individuals with CRPS and healthy controls have supported this concept, although results have been mixed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a cross-sectional study, we examined white matter structure in the brains of people with CRPS and healthy controls (<i>n</i> = 42) using high angular resolution diffusion imaging at 3 Tesla and analysed the data using a fixel-based approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found no significant differences in any diffusion measures between participants with CRPS and controls. Linear regression analyses and equivalence tests demonstrated that fibre density cross-section measures were indistinguishable between the two groups; neither CRPS symptomology nor opioid use could be explained by any white matter structural differences detected by diffusion imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A relatively large sample size and fine-grained methods add confidence to our findings. These results argue against permanent brain changes that prevent recovery in CRPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>In one of the largest studies of white matter structure in complex regional pain syndrome, fixel-based high angular resolution diffusion scans showed no significant difference to controls and were statistically equivalent. This indicates that white matter structural change is unlikely to be of clinical significance in CRPS. This points to functional changes underpinning the deficits associated with the condition and highlights improving neural function through movement-based approaches such as graded motor imagery, graded exposure, desensitisation and functional movement rehabilitation approaches.</p>\u0000 </section>\u0000 </div>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855104","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}
Angélica Maria França Paiva Tibúrcio, Daniel Steffens, Amanda Aparecida Oliveira Leopoldino, Elen Cristina da Mata, Juscelio Pereira da Silva, Juliana Magalhães Machado Barbosa, Isabela Paiva Tibúrcio, Leani Souza Máximo Pereira
Background
Low back pain (LBP) represents the leading cause of years lived with disability (YLD) globally. Among older adults, non-specific LBP constitutes a predominant determinant of functional decline, diminished quality of life (QoL) and considerable socioeconomic burden. This study aimed to assess the impact of pain intensity and disability on healthy-related quality of life (HRQoL) in older adults with non-specific LBP over 12 months.
Methods
602 participants from the BACE-Brazil cohort with acute non-specific LBP were followed for 12 months, 156 were excluded from the analysis due to missing data on the Short Form-36 Questionnaire (SF-36), leaving a final sample of 446 participants. Pain intensity was assessed using the Numerical Rating Scale (NRS), disability with the Roland Morris Disability Questionnaire (RMDQ) and HRQoL with the Short Form-36 (SF-36). Linear regression models examined the relationships between pain, disability and HRQoL, adjusting for sociodemographic and clinical covariates.
Results
In the longitudinal analysis of 446 older adults (mean age 67 ± 7 years, 84.9% women), greater pain intensity was significantly associated with reductions in the physical component of HRQoL, but not with the emotional component. In contrast, worsening disability was associated with declines in both physical and emotional components of HRQoL.
Conclusion
In older adults with acute non-specific LBP, disability exerts a stronger and broader impact on HRQoL than pain intensity. Interventions targeting functional independence may therefore be more effective in preserving HRQoL than strategies focused solely on pain reduction.
Significance Statement
This is the first longitudinal study in a developing country showing that disability, rather than pain intensity, exerts the greatest long-term impact on both physical and emotional quality of life in older adults with acute non- specific low back pain. These findings highlight the need for interventions that prioritise functional preservation and disability reduction, rather than solely focusing on pain relief, to improve outcomes and guide clinical decision-making for this growing and vulnerable population.
{"title":"Is Quality of Life in Older Adults With Non-Specific Low Back Pain Influenced by Pain or Disability? Longitudinal Data From the Back Complaints in the Elders Brazil Cohort","authors":"Angélica Maria França Paiva Tibúrcio, Daniel Steffens, Amanda Aparecida Oliveira Leopoldino, Elen Cristina da Mata, Juscelio Pereira da Silva, Juliana Magalhães Machado Barbosa, Isabela Paiva Tibúrcio, Leani Souza Máximo Pereira","doi":"10.1002/ejp.70191","DOIUrl":"10.1002/ejp.70191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low back pain (LBP) represents the leading cause of years lived with disability (YLD) globally. Among older adults, non-specific LBP constitutes a predominant determinant of functional decline, diminished quality of life (QoL) and considerable socioeconomic burden. This study aimed to assess the impact of pain intensity and disability on healthy-related quality of life (HRQoL) in older adults with non-specific LBP over 12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>602 participants from the BACE-Brazil cohort with acute non-specific LBP were followed for 12 months, 156 were excluded from the analysis due to missing data on the Short Form-36 Questionnaire (SF-36), leaving a final sample of 446 participants. Pain intensity was assessed using the Numerical Rating Scale (NRS), disability with the Roland Morris Disability Questionnaire (RMDQ) and HRQoL with the Short Form-36 (SF-36). Linear regression models examined the relationships between pain, disability and HRQoL, adjusting for sociodemographic and clinical covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the longitudinal analysis of 446 older adults (mean age 67 ± 7 years, 84.9% women), greater pain intensity was significantly associated with reductions in the physical component of HRQoL, but not with the emotional component. In contrast, worsening disability was associated with declines in both physical and emotional components of HRQoL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In older adults with acute non-specific LBP, disability exerts a stronger and broader impact on HRQoL than pain intensity. Interventions targeting functional independence may therefore be more effective in preserving HRQoL than strategies focused solely on pain reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This is the first longitudinal study in a developing country showing that disability, rather than pain intensity, exerts the greatest long-term impact on both physical and emotional quality of life in older adults with acute non- specific low back pain. These findings highlight the need for interventions that prioritise functional preservation and disability reduction, rather than solely focusing on pain relief, to improve outcomes and guide clinical decision-making for this growing and vulnerable population.</p>\u0000 </section>\u0000 </div>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855075","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}
Yoshnee Foolchand, Avgustina Kuzminova, Marc-Henri Louis, Arthur Courtin, Patricia Dessart, André Mouraux, Samar M. Hatem
Objective
To establish normative values for contact heat evoked potentials (CHEP) and cold evoked potentials (CEP), providing a reference for evaluating small fibre neuropathy (SFN) and spinothalamic tract (STT) function.
Methods
Thermal quantitative sensory testing and sensory nerve conduction studies were conducted for screening subjects. CHEP and CEP were recorded from the distal volar forearm and foot dorsum of 80 healthy participants (26–75 years) using a 1.2 cm2 contact thermal stimulator (ramp: 300°C/s, heat: 60°C, cold: 10°C, duration: 200 ms). Age-grouped descriptive statistics were computed. Results between age groups, stimulation sites and sex were compared.
Results
Upper limb CEP showed > 90% detection rates across all ages. N2P2 amplitudes were larger in upper compared to lower limbs (CHEP: p = 0.032; CEP: p < 0.001). N2P2 amplitudes decreased with age for CHEP (p < 0.001) and CEP (p = 0.002). Latencies did not vary between age groups or between limbs (CHEP: p = 0.600; CEP: p = 0.351).
Conclusions
This normative dataset will support the clinical integration of CHEP and CEP as an objective and non-invasive technique for evaluating small fibre and STT function.
Significance Statement
Normative data for contact heat evoked potentials (CHEP) and cold evoked potentials (CEP) were established across age groups in healthy adults, marking a key step toward their use in routine clinical neurophysiology. CHEP and CEP N2P2 amplitudes were consistently larger in upper than lower limbs, with the greatest age-related decline in the feet. Notably, CEP from the upper limbs showed the highest visualisation rates (> 90%) across all ages.
{"title":"Normative Values for Contact Heat and Cold Evoked Potentials","authors":"Yoshnee Foolchand, Avgustina Kuzminova, Marc-Henri Louis, Arthur Courtin, Patricia Dessart, André Mouraux, Samar M. Hatem","doi":"10.1002/ejp.70196","DOIUrl":"10.1002/ejp.70196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To establish normative values for contact heat evoked potentials (CHEP) and cold evoked potentials (CEP), providing a reference for evaluating small fibre neuropathy (SFN) and spinothalamic tract (STT) function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thermal quantitative sensory testing and sensory nerve conduction studies were conducted for screening subjects. CHEP and CEP were recorded from the distal volar forearm and foot dorsum of 80 healthy participants (26–75 years) using a 1.2 cm<sup>2</sup> contact thermal stimulator (ramp: 300°C/s, heat: 60°C, cold: 10°C, duration: 200 ms). Age-grouped descriptive statistics were computed. Results between age groups, stimulation sites and sex were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upper limb CEP showed > 90% detection rates across all ages. N2P2 amplitudes were larger in upper compared to lower limbs (CHEP: <i>p</i> = 0.032; CEP: <i>p</i> < 0.001). N2P2 amplitudes decreased with age for CHEP (<i>p</i> < 0.001) and CEP (<i>p</i> = 0.002). Latencies did not vary between age groups or between limbs (CHEP: <i>p</i> = 0.600; CEP: <i>p</i> = 0.351).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This normative dataset will support the clinical integration of CHEP and CEP as an objective and non-invasive technique for evaluating small fibre and STT function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Normative data for contact heat evoked potentials (CHEP) and cold evoked potentials (CEP) were established across age groups in healthy adults, marking a key step toward their use in routine clinical neurophysiology. CHEP and CEP N2P2 amplitudes were consistently larger in upper than lower limbs, with the greatest age-related decline in the feet. Notably, CEP from the upper limbs showed the highest visualisation rates (> 90%) across all ages.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849556","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}
Karin Due Bruun, Maria Charlotte Reiersoel Moerkeberg, Julie Roenne Pedersen, Daniel Broholm, Morten Rune Blichfeldt-Eckhardt, Lotte Abildgren
Background
The opioid system is involved in the regulation of pain as well as stress homeostasis. Stress-induced opioid dysregulation has been proposed as a mechanism for pain development in patients with fibromyalgia (FM) and chronic low back pain (cLBP). However, the evidence to support this hypothesis is conflicting.
Methods
We conducted a systematic literature search in MEDLINE, EMBASE, and the Cochrane Library database to investigate whether patients with FM or cLBP exhibit (1) different levels of endogenous opioids or anti-opioids in body fluids or tissue samples, or (2) altered levels of opioid receptor expression or availability compared to pain-free controls.
Results
We identified 33 studies eligible for inclusion in the review, investigating 863 patients and 636 pain-free controls. Three meta-analyses of beta-endorphin levels in blood and cerebrospinal fluid (CSF) were performed, revealing no significant differences between patients with FM or cLBP and controls. However, the grading of the evidence was very low. Mu-opioid receptor (MOR) dysfunction emerged as a potential feature of FM, with some evidence suggesting reduced MOR binding in the brain and decreased MOR expression in immune cells.
Conclusions
Current evidence does not support altered peripheral endorphin levels in FM or cLBP, while emerging PET findings indicate reduced central MOR availability in FM. These results suggest receptor-level dysregulation rather than peripheral opioid deficits. Limitations mainly arose from low sample sizes and inadequate study methodologies, underscoring the need for well-designed studies with larger sample sizes to clarify the role of endogenous opioid dysfunction in FM and cLBP.
Significance
This systematic review highlights emerging evidence of mu-opioid receptor dysfunction in fibromyalgia, despite no consistent differences in beta-endorphin levels. The findings underscore significant methodological limitations in existing studies and point to the need for rigorous, well-powered research to clarify the role of endogenous opioid dysregulation in chronic pain.
{"title":"A Systematic Review With Meta-Analysis of Endogenous Opioid System Biomarkers in Patients With Chronic Axial Pain, Chronic Widespread Pain, and Fibromyalgia","authors":"Karin Due Bruun, Maria Charlotte Reiersoel Moerkeberg, Julie Roenne Pedersen, Daniel Broholm, Morten Rune Blichfeldt-Eckhardt, Lotte Abildgren","doi":"10.1002/ejp.70192","DOIUrl":"10.1002/ejp.70192","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The opioid system is involved in the regulation of pain as well as stress homeostasis. Stress-induced opioid dysregulation has been proposed as a mechanism for pain development in patients with fibromyalgia (FM) and chronic low back pain (cLBP). However, the evidence to support this hypothesis is conflicting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic literature search in MEDLINE, EMBASE, and the Cochrane Library database to investigate whether patients with FM or cLBP exhibit (1) different levels of endogenous opioids or anti-opioids in body fluids or tissue samples, or (2) altered levels of opioid receptor expression or availability compared to pain-free controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 33 studies eligible for inclusion in the review, investigating 863 patients and 636 pain-free controls. Three meta-analyses of beta-endorphin levels in blood and cerebrospinal fluid (CSF) were performed, revealing no significant differences between patients with FM or cLBP and controls. However, the grading of the evidence was very low. Mu-opioid receptor (MOR) dysfunction emerged as a potential feature of FM, with some evidence suggesting reduced MOR binding in the brain and decreased MOR expression in immune cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Current evidence does not support altered peripheral endorphin levels in FM or cLBP, while emerging PET findings indicate reduced central MOR availability in FM. These results suggest receptor-level dysregulation rather than peripheral opioid deficits. Limitations mainly arose from low sample sizes and inadequate study methodologies, underscoring the need for well-designed studies with larger sample sizes to clarify the role of endogenous opioid dysfunction in FM and cLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This systematic review highlights emerging evidence of mu-opioid receptor dysfunction in fibromyalgia, despite no consistent differences in beta-endorphin levels. The findings underscore significant methodological limitations in existing studies and point to the need for rigorous, well-powered research to clarify the role of endogenous opioid dysregulation in chronic pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849574","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}
Marta Spinoni, Cristian Di Gesto, Maria Grazia Porpora, Caterina Grano
Background
Endometriosis is a prevalent condition characterised by chronic pelvic pain, significantly impacting women's quality of life and well-being. Pain catastrophizing is a cognitive tendency of exaggerated worrying, a sense of helplessness, and amplification of distressing thoughts in response to pain. According to the Fear-Avoidance Model, catastrophizing contributes to prolonged pain interference and mood disorders. This longitudinal study examines the relationship between pain catastrophizing, pain interference, and depressive symptoms in patients with endometriosis.
Methods
A sample of 128 cisgender women with endometriosis recruited from online patient associations completed self-report measures assessing pain catastrophizing, pain interference, and depressive symptoms at baseline (T1) and after 6 months (T2). A mediation model examining the indirect effect of pain catastrophizing on depressive symptoms through pain interference was tested. The pelvic pain level was considered as a covariate in the model.
Results
More than half of the sample reported depressive symptoms above the cut-off. Pain catastrophizing at T1 significantly predicted depressive symptoms at T2. Pain interference partially mediated this relationship.
Conclusions
Our findings indicate that heightened levels of catastrophizing correlate with increased pain interference, which, in turn, predicts elevated depressive symptoms over time. Findings suggest that by targeting catastrophizing tendencies, clinicians may help mitigate depressive symptomatology.
Significance Statement
This longitudinal study investigates for the first time the impact of pain catastrophizing on pain interference and depressive symptoms over time in cisgender women with endometriosis. Findings indicated both a direct influence of pain catastrophizing on depressive symptomatology and an indirect effect via increased pain interference, in line with the Fear-Avoidance Model. These findings underscore the importance of targeting pain catastrophizing tendencies in interventions aimed at improving the well-being of patients affected by endometriosis.
{"title":"The Role of Catastrophizing in Enhancing Pain Interference and Depressive Symptoms in Endometriosis: A Longitudinal Examination","authors":"Marta Spinoni, Cristian Di Gesto, Maria Grazia Porpora, Caterina Grano","doi":"10.1002/ejp.70198","DOIUrl":"10.1002/ejp.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endometriosis is a prevalent condition characterised by chronic pelvic pain, significantly impacting women's quality of life and well-being. Pain catastrophizing is a cognitive tendency of exaggerated worrying, a sense of helplessness, and amplification of distressing thoughts in response to pain. According to the Fear-Avoidance Model, catastrophizing contributes to prolonged pain interference and mood disorders. This longitudinal study examines the relationship between pain catastrophizing, pain interference, and depressive symptoms in patients with endometriosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A sample of 128 cisgender women with endometriosis recruited from online patient associations completed self-report measures assessing pain catastrophizing, pain interference, and depressive symptoms at baseline (T1) and after 6 months (T2). A mediation model examining the indirect effect of pain catastrophizing on depressive symptoms through pain interference was tested. The pelvic pain level was considered as a covariate in the model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>More than half of the sample reported depressive symptoms above the cut-off. Pain catastrophizing at T1 significantly predicted depressive symptoms at T2. Pain interference partially mediated this relationship.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings indicate that heightened levels of catastrophizing correlate with increased pain interference, which, in turn, predicts elevated depressive symptoms over time. Findings suggest that by targeting catastrophizing tendencies, clinicians may help mitigate depressive symptomatology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This longitudinal study investigates for the first time the impact of pain catastrophizing on pain interference and depressive symptoms over time in cisgender women with endometriosis. Findings indicated both a direct influence of pain catastrophizing on depressive symptomatology and an indirect effect via increased pain interference, in line with the Fear-Avoidance Model. These findings underscore the importance of targeting pain catastrophizing tendencies in interventions aimed at improving the well-being of patients affected by endometriosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12742274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833548","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}
Knee osteoarthritis (OA) affects approximately 10% of the general population. Of these, nearly 20% of patients undergo total knee arthroplasty (TKA). A proportion subsequently develops long-term opioid use, yet comprehensive evaluations of perioperative risk factors remain limited.
Methods
A total of 15,051 patients with knee OA who underwent TKA between 2002 and 2018 were included. Our primary analysis used a Least Absolute Shrinkage and Selection Operator (LASSO)–Elastic Net logistic regression model with a 70/30 training–validation split to identify predictors of long-term opioid use and to estimate model performance using the area under the receiver operating characteristic curve (AUC) and calibration. As supplementary analyses, hierarchical logistic regression models progressively incorporated demographic, preoperative, in-hospital, and early post-discharge variables.
Results
Overall, 1029 patients were identified as long-term opioid users. The LASSO–Elastic Net model achieved an AUC of 0.8213 (95% CI: 0.8080–0.8347). The AUCs of the hierarchical logistic models were 0.7523 (95% CI: 0.7364–0.7681) for demographic and preoperative factors (Model 1), 0.7682 (95% CI: 0.7534–0.7829) with added hospitalisation factors (Model 2), and 0.8251 (95% CI: 0.8119–0.8383) after further including post-discharge variables (Model 3).
Conclusion
This study systematically identifies risk factors for long-term opioid use across different phases of TKA care. A predictive model based on LASSO–Elastic analysis demonstrated an AUC of 0.8213, highlighting its potential for early identification of high-risk patients.
Significance Statement
Using a population-based analysis, this study identifies risk factors for prolonged opioid use following TKA, aiding clinicians in early recognition and targeted preventive strategies.
{"title":"Prediction Model for Factors Associated With Long-Term Opioid Use Following Total Knee Arthroplasty: A Retrospective Population-Based Study","authors":"Pin-Hung Yeh, Shun-Fa Yang, Jing-Yang Huang, Chao-Bin Yeh","doi":"10.1002/ejp.70195","DOIUrl":"10.1002/ejp.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Knee osteoarthritis (OA) affects approximately 10% of the general population. Of these, nearly 20% of patients undergo total knee arthroplasty (TKA). A proportion subsequently develops long-term opioid use, yet comprehensive evaluations of perioperative risk factors remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 15,051 patients with knee OA who underwent TKA between 2002 and 2018 were included. Our primary analysis used a Least Absolute Shrinkage and Selection Operator (LASSO)–Elastic Net logistic regression model with a 70/30 training–validation split to identify predictors of long-term opioid use and to estimate model performance using the area under the receiver operating characteristic curve (AUC) and calibration. As supplementary analyses, hierarchical logistic regression models progressively incorporated demographic, preoperative, in-hospital, and early post-discharge variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 1029 patients were identified as long-term opioid users. The LASSO–Elastic Net model achieved an AUC of 0.8213 (95% CI: 0.8080–0.8347). The AUCs of the hierarchical logistic models were 0.7523 (95% CI: 0.7364–0.7681) for demographic and preoperative factors (Model 1), 0.7682 (95% CI: 0.7534–0.7829) with added hospitalisation factors (Model 2), and 0.8251 (95% CI: 0.8119–0.8383) after further including post-discharge variables (Model 3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study systematically identifies risk factors for long-term opioid use across different phases of TKA care. A predictive model based on LASSO–Elastic analysis demonstrated an AUC of 0.8213, highlighting its potential for early identification of high-risk patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Using a population-based analysis, this study identifies risk factors for prolonged opioid use following TKA, aiding clinicians in early recognition and targeted preventive strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12740543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833481","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}
Emma L. Karran, Aidan G. Cashin, Alessandro Chiarotto, Saurab Sharma, Trevor Barker, Mark A. Boyd, Lara J. Maxwell, Vina Mohabir, Jennifer Petkovic, Peter Tugwell, G. Lorimer Moseley
{"title":"Standardising the Collection of Socio-Demographic Data in Pain Research","authors":"Emma L. Karran, Aidan G. Cashin, Alessandro Chiarotto, Saurab Sharma, Trevor Barker, Mark A. Boyd, Lara J. Maxwell, Vina Mohabir, Jennifer Petkovic, Peter Tugwell, G. Lorimer Moseley","doi":"10.1002/ejp.70194","DOIUrl":"10.1002/ejp.70194","url":null,"abstract":"","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793515","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}
{"title":"The Unserved Majority: The Urgent Need to Address the Mild-Impact Chronic Pain Population","authors":"Flaminia Coluzzi","doi":"10.1002/ejp.70189","DOIUrl":"10.1002/ejp.70189","url":null,"abstract":"","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780453","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}
Michael Nørregaard Vinkel, Gija Rackauskaite, Mette Thorup, Andrea Truini, John Rosendahl Østergaard, Hatice Tankisi, Nanna Brix Finnerup
Background
Pain is common in people with cerebral palsy. Despite the presence of central nervous system injury, it is unknown whether central neuropathic pain occurs in cerebral palsy and whether unpleasant, abnormal sensations such as dysesthesia are present. The study aims to examine the presence of sensory abnormalities and neuropathic pain in youth with cerebral palsy and relate these findings to specific brain injuries.
Methods
This cross-sectional observational study examines 27 ambulant youth with cerebral palsy and 48 healthy controls aged 15–22 using structured interviews, detailed bedside examinations, laser evoked potentials, quantitative sensory testing and MRI.
Results
The prevalence of self-reported sensory abnormalities in the cerebral palsy group was lower than found using bedside sensory mapping (41% vs. 74%, p = 0.003) and quantitative sensory testing (41% vs. 70%, p = 0.021). Furthermore, three had evoked dysesthesia. Ongoing or recurrent pain occurred in 70% of youth with cerebral palsy, without evidence of central neuropathic pain. The relative risk of having sensory loss was 3.2 (95% CI 1.47–7.00) when an injury to the spinothalamic tract, thalamus, insula, or somatosensory cortex was present, while the relative risk of sensory gain was 5.3 (95% CI 0.78–35.85) with the presence of white matter injury from periventricular leucomalacia.
Conclusions
We recommend addressing sensory function and dysesthesia in future studies and cerebral palsy follow-up programs. Brain injury patterns may predict sensory loss or gain and distinct somatosensory topographies could clarify these mechanisms. These insights may enable earlier identification of sensory abnormalities in cerebral palsy.
Significance Statement
1) This study highlights the high prevalence yet underrecognition of sensory abnormalities and pain in individuals with cerebral palsy. 2) It explores the subjective experience and perception of sensory abnormalities and is the first to identify and characterize dysesthesia in this population. 3) The findings demonstrate that pain is common among young, ambulant individuals with cerebral palsy; however, central neuropathic pain appears to be absent despite underlying central nervous system injury.
背景：疼痛在脑瘫患者中很常见。尽管存在中枢神经系统损伤，但尚不清楚脑瘫患者是否发生中枢神经性疼痛，以及是否存在不愉快的异常感觉，如感觉不良。该研究旨在检查青少年脑瘫患者感觉异常和神经性疼痛的存在，并将这些发现与特定的脑损伤联系起来。方法：采用结构化访谈、详细床边检查、激光诱发电位、定量感觉测试和MRI对27例脑瘫青年和48例15-22岁的健康对照进行横断面观察性研究。结果：脑瘫组自我报告感觉异常的发生率低于床边感觉测图（41%比74%，p = 0.003）和定量感觉测试（41%比70%，p = 0.021）。此外，其中3例引起了感觉不良。70%的青年脑瘫患者出现持续或复发性疼痛，没有中枢神经性疼痛的证据。当脊髓丘脑束、丘脑、脑岛或体感觉皮层受到损伤时，感觉丧失的相对风险为3.2 (95% CI 1.47-7.00)，而当脑室周围白质软化造成白质损伤时，感觉获得的相对风险为5.3 （95% CI 0.78-35.85）。结论：我们建议在未来的研究和脑瘫随访计划中关注感觉功能和感觉障碍。脑损伤模式可以预测感觉丧失或获得，不同的体感地形可以阐明这些机制。这些见解可能有助于早期识别脑瘫的感觉异常。意义声明：1)本研究强调了脑瘫患者的感觉异常和疼痛的高患病率，但未被充分认识。2)它探索了感觉异常的主观体验和感知，并且是第一个识别和表征该人群的感觉障碍。3)研究结果表明，疼痛在年轻、活动的脑瘫患者中很常见；然而，尽管中枢神经系统损伤，中枢神经性疼痛似乎不存在。
{"title":"Somatosensory Abnormalities, Dysesthesia and Central Neuropathic Pain in Youth With Cerebral Palsy","authors":"Michael Nørregaard Vinkel, Gija Rackauskaite, Mette Thorup, Andrea Truini, John Rosendahl Østergaard, Hatice Tankisi, Nanna Brix Finnerup","doi":"10.1002/ejp.70188","DOIUrl":"10.1002/ejp.70188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pain is common in people with cerebral palsy. Despite the presence of central nervous system injury, it is unknown whether central neuropathic pain occurs in cerebral palsy and whether unpleasant, abnormal sensations such as dysesthesia are present. The study aims to examine the presence of sensory abnormalities and neuropathic pain in youth with cerebral palsy and relate these findings to specific brain injuries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional observational study examines 27 ambulant youth with cerebral palsy and 48 healthy controls aged 15–22 using structured interviews, detailed bedside examinations, laser evoked potentials, quantitative sensory testing and MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of self-reported sensory abnormalities in the cerebral palsy group was lower than found using bedside sensory mapping (41% vs. 74%, <i>p</i> = 0.003) and quantitative sensory testing (41% vs. 70%, <i>p</i> = 0.021). Furthermore, three had evoked dysesthesia. Ongoing or recurrent pain occurred in 70% of youth with cerebral palsy, without evidence of central neuropathic pain. The relative risk of having sensory loss was 3.2 (95% CI 1.47–7.00) when an injury to the spinothalamic tract, thalamus, insula, or somatosensory cortex was present, while the relative risk of sensory gain was 5.3 (95% CI 0.78–35.85) with the presence of white matter injury from periventricular leucomalacia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We recommend addressing sensory function and dysesthesia in future studies and cerebral palsy follow-up programs. Brain injury patterns may predict sensory loss or gain and distinct somatosensory topographies could clarify these mechanisms. These insights may enable earlier identification of sensory abnormalities in cerebral palsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>1) This study highlights the high prevalence yet underrecognition of sensory abnormalities and pain in individuals with cerebral palsy. 2) It explores the subjective experience and perception of sensory abnormalities and is the first to identify and characterize dysesthesia in this population. 3) The findings demonstrate that pain is common among young, ambulant individuals with cerebral palsy; however, central neuropathic pain appears to be absent despite underlying central nervous system injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773916","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}
<p>The journal recently published a position paper by Liang et al. (<span>2025</span>) titled “Phenotyping chronic pain and neuropathic pain in population studies.” There can be little argument about the central proposition of the paper—that we need to have consistent approaches to defining commonly occurring categories of chronic pain and to identifying meaningful phenotypes. The current lack of clarity and consistency undermines both our understanding of the overall population burden of chronic pain and progress on the potential of precision medicine to improve how treatment effectiveness is assessed in clinical populations.</p><p>The pyramid model for phenotyping based on chronic neuropathic pain that is proposed in the paper succinctly captures the different goals of epidemiological research spanning general population-level studies through to richly characterised clinical cohort studies, with indicative approaches to phenotyping matched to those goals. Also implicit in the pyramid model is the trade-off between generalisability and precision (breadth versus depth) required at different levels of the model, according to the primary goal at each level of the pyramid. While the paper outlines the substantial progress for neuropathic pain conditions, a significant challenge remains to replicate this for other common forms of chronic pain.</p><p>Efforts to standardise or harmonise data collection and phenotyping are essential, and will likely reduce variation in prevalence due to methodological differences between studies. When consistent definitions are used, other drivers of differences in prevalence can be identified, notably geographical and equity-related factors (Zimmer et al. <span>2022</span>). These include groups exposed to multiple, often intersecting forms of marginalisation across ethnicity, gender, disability, and socioeconomic position. Yet, perhaps paradoxically, the large-scale studies and biobanks that exist are overwhelmingly from high-income countries and settings, and even within these settings consistently under-recruit from and therefore under-represent the priority populations most at risk of high pain burden. In the rapidly developing field of clinical risk prediction modelling, there are related concerns about model fairness if models are developed from large datasets where minority populations are under-represented, and the accuracy of risk prediction in these populations is more uncertain (Riley et al. <span>2025</span>).</p><p>The authors point out that progress towards developing tailored interventions needs more clarity and consistency in identifying biopsychosocial contributors of pain, and this in turn depends on consistency in case definitions and phenotyping. Collectively, this should be underpinned by conceptually coherent models of how risk factors work together over time that can be empirically tested and refined. Cohort studies are particularly valuable in this context, as they collect longitudinal data that
该杂志最近发表了Liang等人（2025）的一篇题为“人口研究中的慢性疼痛和神经性疼痛表型”的立场论文。关于本文的中心命题，我们需要有一致的方法来定义常见的慢性疼痛类别，并确定有意义的表型，这一点几乎没有争议。目前缺乏清晰度和一致性，既破坏了我们对慢性疼痛总体人口负担的理解，也破坏了精准医学在改善临床人群治疗效果评估方面的潜力。本文提出的基于慢性神经性疼痛的表型金字塔模型简洁地捕捉了流行病学研究的不同目标，从一般人群水平的研究到特征丰富的临床队列研究，并采用与这些目标相匹配的指示性表型方法。金字塔模型中隐含的另一个问题是，根据金字塔每一层的主要目标，在模型的不同层次所需的通用性和精确性（广度与深度）之间进行权衡。虽然论文概述了神经性疼痛条件的实质性进展，但对其他常见形式的慢性疼痛复制这一重大挑战仍然存在。标准化或协调数据收集和表型的努力是必不可少的，并且可能会减少由于研究之间的方法差异而导致的患病率差异。当使用一致的定义时，可以确定患病率差异的其他驱动因素，特别是地理和公平相关因素（Zimmer et al. 2022）。这些群体包括因种族、性别、残疾和社会经济地位而面临多重、往往是交叉形式的边缘化的群体。然而，也许矛盾的是，现有的大规模研究和生物库绝大多数来自高收入国家和地区，即使在这些地区，也一直没有从高疼痛负担风险最高的优先人群中招募人员，因此代表性不足。在快速发展的临床风险预测建模领域，如果模型是从少数民族人群代表性不足的大型数据集开发的，并且这些人群的风险预测准确性更不确定，则存在与模型公平性相关的担忧（Riley et al. 2025）。作者指出，开发量身定制的干预措施的进展需要在识别疼痛的生物心理社会因素方面更加清晰和一致，而这反过来又取决于病例定义和表型的一致性。总的来说，这应该以概念上连贯的模型为基础，这些模型表明风险因素如何随着时间的推移而共同作用，这些模型可以经过经验检验和改进。在这种情况下，队列研究特别有价值，因为它们收集纵向数据，允许检查疼痛轨迹和随时间的因果关系。该立场文件还强调，形成大规模的研究联盟对于在疼痛研究的关键领域取得进展非常重要（hsambert et al. 2023）。随着大型财团和生物银行的经验积累，我们对它们潜在的好处和挑战的理解也在不断加深。其中一个挑战是评估如何在更广泛的疼痛研究领域中最好地定位大数据研究，并确保有效利用现有资源来捕获不同的人群和背景。本文链接至Liang等人的论文。要查看本文，请访问https://doi.org/10.1002/ejp.70146。
{"title":"Commentary on “Phenotyping Chronic Pain and Neuropathic Pain in Population Studies”","authors":"Fiona M. Blyth, Saman Khalatbari-Soltani","doi":"10.1002/ejp.70193","DOIUrl":"10.1002/ejp.70193","url":null,"abstract":"<p>The journal recently published a position paper by Liang et al. (<span>2025</span>) titled “Phenotyping chronic pain and neuropathic pain in population studies.” There can be little argument about the central proposition of the paper—that we need to have consistent approaches to defining commonly occurring categories of chronic pain and to identifying meaningful phenotypes. The current lack of clarity and consistency undermines both our understanding of the overall population burden of chronic pain and progress on the potential of precision medicine to improve how treatment effectiveness is assessed in clinical populations.</p><p>The pyramid model for phenotyping based on chronic neuropathic pain that is proposed in the paper succinctly captures the different goals of epidemiological research spanning general population-level studies through to richly characterised clinical cohort studies, with indicative approaches to phenotyping matched to those goals. Also implicit in the pyramid model is the trade-off between generalisability and precision (breadth versus depth) required at different levels of the model, according to the primary goal at each level of the pyramid. While the paper outlines the substantial progress for neuropathic pain conditions, a significant challenge remains to replicate this for other common forms of chronic pain.</p><p>Efforts to standardise or harmonise data collection and phenotyping are essential, and will likely reduce variation in prevalence due to methodological differences between studies. When consistent definitions are used, other drivers of differences in prevalence can be identified, notably geographical and equity-related factors (Zimmer et al. <span>2022</span>). These include groups exposed to multiple, often intersecting forms of marginalisation across ethnicity, gender, disability, and socioeconomic position. Yet, perhaps paradoxically, the large-scale studies and biobanks that exist are overwhelmingly from high-income countries and settings, and even within these settings consistently under-recruit from and therefore under-represent the priority populations most at risk of high pain burden. In the rapidly developing field of clinical risk prediction modelling, there are related concerns about model fairness if models are developed from large datasets where minority populations are under-represented, and the accuracy of risk prediction in these populations is more uncertain (Riley et al. <span>2025</span>).</p><p>The authors point out that progress towards developing tailored interventions needs more clarity and consistency in identifying biopsychosocial contributors of pain, and this in turn depends on consistency in case definitions and phenotyping. Collectively, this should be underpinned by conceptually coherent models of how risk factors work together over time that can be empirically tested and refined. Cohort studies are particularly valuable in this context, as they collect longitudinal data that","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762484","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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