Low back pain imposes a substantial global health burden, impairing productivity and quality of life. Emerging evidence implicates systemic inflammation in its pathogenesis. The Systemic Immune-Inflammation Index (SII), a validated inflammatory biomarker, may elucidate this relationship. This study investigated the SII–low back pain association.
Methods
The study employed data from the National Health and Nutrition Examination Survey (NHANES) for the cycles 2001–2004 and 2009–2010. The connection of SII with low back pain was investigated using a weighted multivariable regression analysis model. Subgroup analyses were conducted, stratifying participants by gender and age. Restricted cubic spline (RCS) examined potential nonlinear dose–response relationships.
Results
This research analysed 17,286 subjects. Following log-transformation of SII, a fully adjusted model demonstrated that SII was significantly associated with low back pain (OR = 1.41; 95% CI: [1.31, 1.52]; p < 0.001). Participants in the highest quartile of SII had a 66% higher probability of having low back pain compared with those in the lowest quartile (OR = 1.66; 95% CI: [1.44, 1.92]; p < 0.001). This positive association remained significant in both sexes (OR = 1.37; 95% CI: [1.19, 1.57]; p < 0.001; OR = 1.45; 95% CI: [1.33, 1.59]; p < 0.001). In the 20–40 and 40–60 years age groups, the study found a similar association (OR = 2.05; 95% CI: [1.65, 2.55]; p < 0.001; OR = 1.46; 95% CI: [1.14, 1.86]; p = 0.004).
Conclusions
Higher SII values show a significant correlation with a greater likelihood of developing low back pain.
Significance Statement
This large-scale study reveals, for the first time, a significant association between the systemic immune-inflammation index (SII) and low back pain in U.S. adults. Through stratified analysis, our study provides potential stratification indicators for the early prediction of low back pain.
{"title":"Association Between Systemic Immune-Inflammation Index and Low Back Pain in American Adults: Evidence From a Large Population-Based Study","authors":"Chen Yuyang","doi":"10.1002/ejp.70179","DOIUrl":"10.1002/ejp.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low back pain imposes a substantial global health burden, impairing productivity and quality of life. Emerging evidence implicates systemic inflammation in its pathogenesis. The Systemic Immune-Inflammation Index (SII), a validated inflammatory biomarker, may elucidate this relationship. This study investigated the SII–low back pain association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study employed data from the National Health and Nutrition Examination Survey (NHANES) for the cycles 2001–2004 and 2009–2010. The connection of SII with low back pain was investigated using a weighted multivariable regression analysis model. Subgroup analyses were conducted, stratifying participants by gender and age. Restricted cubic spline (RCS) examined potential nonlinear dose–response relationships.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This research analysed 17,286 subjects. Following log-transformation of SII, a fully adjusted model demonstrated that SII was significantly associated with low back pain (OR = 1.41; 95% CI: [1.31, 1.52]; <i>p</i> < 0.001). Participants in the highest quartile of SII had a 66% higher probability of having low back pain compared with those in the lowest quartile (OR = 1.66; 95% CI: [1.44, 1.92]; <i>p</i> < 0.001). This positive association remained significant in both sexes (OR = 1.37; 95% CI: [1.19, 1.57]; <i>p</i> < 0.001; OR = 1.45; 95% CI: [1.33, 1.59]; <i>p</i> < 0.001). In the 20–40 and 40–60 years age groups, the study found a similar association (OR = 2.05; 95% CI: [1.65, 2.55]; <i>p</i> < 0.001; OR = 1.46; 95% CI: [1.14, 1.86]; <i>p</i> = 0.004).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher SII values show a significant correlation with a greater likelihood of developing low back pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This large-scale study reveals, for the first time, a significant association between the systemic immune-inflammation index (SII) and low back pain in U.S. adults. Through stratified analysis, our study provides potential stratification indicators for the early prediction of low back pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647859","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}
Carles Espinós Ramírez, Pere Castellví Obiols, David Martínez-Rodríguez, Mireia Raynard, Blanca Viscasillas Draper, Paula Masgoret, Cristina Rodríguez Cosmen, Laura Subirana Giménez, Maria Martinez García, Gerard Mestres, Martha Melo, Alexia Nebot Galindo, Natalia Montero Gaig, Virginia Sánchez-Migallón, David Valencia Royo, Núria Lara Pacheco Comino, Inés Bermejo Perez, Cristina Santos Farré, Lluís Toll Salillas, Arnau Alonso Gelabert, Marta Homs, Patricia Ribas, Claudia Teixell, Ana María Plaza Moral, Beatriz Tena, Adrián Fernández Castiñeira, Mireia Armengol Gay, Beatriz Fort Pelai, Carolina García Bartoló, Carolina Mestre Iniesta, Anna Peig Font, Paula Gil Esteller, Jean Louis Clave, Sandra Gasca Pera, Astrid Batalla, Virginia Raduá Giménez, Gisela Roca Amatria
Background
Chronic postsurgical pain (CPSP) following caesarean delivery remains poorly studied despite being one of the most common surgeries and its potential devastating consequences on patients and their newborn babies. We conducted a prospective evaluation of data from a large multicentric cohort to calculate its prevalence, describe its characteristics, risk factors associated and measure its consequences on patients' quality of life and daily functioning.
Methods
A prospective multicentre observational study with women undergoing elective caesarean section. All participants were contacted at 3 months postoperatively to assess the presence or absence of persistent pain. Pain patients were assessed in person to collect data from a focused clinical interview, a targeted physical exam and a set of comprehensive quality of life and functional questionnaires.
Results
CPSP was diagnosed in 69 women (14.59%) of the 514 total participants. Most (94.20%) described their pain with somatic-like characteristics. 46.38% also screened positive for neuropathic features and 41.51% fulfilled diagnostic criteria for chronic pelvic pain. Preoperative SF-12 and catastrophic scale and worse postoperative pain at 24 h were related to a higher risk of developing CPSP. Patients with CPSP reported moderate interference in mood, general activity and occupational functioning being more severe in patients with neuropathic pain.
Conclusions
The prevalence of persistent pain after caesarean delivery is noticeably high for such a common, simple and benign surgical procedure. A subset of patients develops mixed neuropathic pain and chronic pelvic pain syndromes. CPSP causes a significant negative impact on quality of life, particularly among patients with neuropathic symptoms.
Significance Statement
This manuscript presents the analysis of the results of a multicentre study regarding the prevalence of CPSP after a caesarean section. Moreover, we have also looked for clinical characteristics of CPSP and its effects on quality of life and daily functioning. The study we describe provides new insights about which the incidence, type, location of CPSP after a caesarean section and association with chronic pelvic pain. It also shows the impact that having CPSP has on these patients' quality of life and activities of daily living.
{"title":"Acute Postoperative Pain After Caesarean Section, Intensity and Management: A Cohort Multicentre Study","authors":"Carles Espinós Ramírez, Pere Castellví Obiols, David Martínez-Rodríguez, Mireia Raynard, Blanca Viscasillas Draper, Paula Masgoret, Cristina Rodríguez Cosmen, Laura Subirana Giménez, Maria Martinez García, Gerard Mestres, Martha Melo, Alexia Nebot Galindo, Natalia Montero Gaig, Virginia Sánchez-Migallón, David Valencia Royo, Núria Lara Pacheco Comino, Inés Bermejo Perez, Cristina Santos Farré, Lluís Toll Salillas, Arnau Alonso Gelabert, Marta Homs, Patricia Ribas, Claudia Teixell, Ana María Plaza Moral, Beatriz Tena, Adrián Fernández Castiñeira, Mireia Armengol Gay, Beatriz Fort Pelai, Carolina García Bartoló, Carolina Mestre Iniesta, Anna Peig Font, Paula Gil Esteller, Jean Louis Clave, Sandra Gasca Pera, Astrid Batalla, Virginia Raduá Giménez, Gisela Roca Amatria","doi":"10.1002/ejp.70183","DOIUrl":"https://doi.org/10.1002/ejp.70183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic postsurgical pain (CPSP) following caesarean delivery remains poorly studied despite being one of the most common surgeries and its potential devastating consequences on patients and their newborn babies. We conducted a prospective evaluation of data from a large multicentric cohort to calculate its prevalence, describe its characteristics, risk factors associated and measure its consequences on patients' quality of life and daily functioning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective multicentre observational study with women undergoing elective caesarean section. All participants were contacted at 3 months postoperatively to assess the presence or absence of persistent pain. Pain patients were assessed in person to collect data from a focused clinical interview, a targeted physical exam and a set of comprehensive quality of life and functional questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CPSP was diagnosed in 69 women (14.59%) of the 514 total participants. Most (94.20%) described their pain with somatic-like characteristics. 46.38% also screened positive for neuropathic features and 41.51% fulfilled diagnostic criteria for chronic pelvic pain. Preoperative SF-12 and catastrophic scale and worse postoperative pain at 24 h were related to a higher risk of developing CPSP. Patients with CPSP reported moderate interference in mood, general activity and occupational functioning being more severe in patients with neuropathic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The prevalence of persistent pain after caesarean delivery is noticeably high for such a common, simple and benign surgical procedure. A subset of patients develops mixed neuropathic pain and chronic pelvic pain syndromes. CPSP causes a significant negative impact on quality of life, particularly among patients with neuropathic symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This manuscript presents the analysis of the results of a multicentre study regarding the prevalence of CPSP after a caesarean section. Moreover, we have also looked for clinical characteristics of CPSP and its effects on quality of life and daily functioning. The study we describe provides new insights about which the incidence, type, location of CPSP after a caesarean section and association with chronic pelvic pain. It also shows the impact that having CPSP has on these patients' quality of life and activities of daily living.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619200","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}
<div> <section> <h3> Background and Objective</h3> <p>Although calcitonin gene-related peptide (CGRP) has emerged as a promising therapeutic target in migraine management, current clinical evidence regarding its dynamic variations in paediatric migraine populations remains inconclusive. We conducted a meta-analysis to explore the relationship between blood CGRP levels and paediatric migraine.</p> </section> <section> <h3> Databases and Data Treatment</h3> <p>We systematically searched for observational studies that reported CGRP levels in paediatric migraine published in English from the PubMed, Web of Science, and Embase electronic databases, or in Chinese from the Chinese National Knowledge Infrastructure and the WanFang Med database. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The quality of evidence for each outcome was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.</p> </section> <section> <h3> Results</h3> <p>Of the 1134 identified studies, eight were eligible for inclusion. There was a ‘Moderate’ level of evidence demonstrating significantly elevated CGRP levels in children with migraine compared to controls (standardised mean difference [SMD] = 1.44, 95% CI 0.61–2.31). Stratification analysis showed the ‘Low’ level of evidence revealed higher levels during both ictal (SMD = 2.39, 95% CI 0.59–4.19) and interictal phases (SMD = 1.27, 95% CI 0.54–1.99). ‘Very low’ quality of evidence supported paediatric migraine patients with (SMD = 1.47, 95% CI 0.67–2.27) and without (SMD = 1.11, 95% CI 0.50–1.72) aura had higher CGRP levels than non-migraine controls.</p> </section> <section> <h3> Conclusions</h3> <p>Our findings suggest that CGRP levels may be a potential diagnostic biomarker and prophylactic therapeutic target for paediatric migraine, but need high-quality longitudinal studies to validate.</p> </section> <section> <h3> Significance Statement</h3> <p>This systematic review and meta-analysis provides significant evidence that CGRP levels serve as a potential diagnostic biomarker for migraine in children and adolescents. Future research should further explore the diagnostic value of CGRP levels in this population. However, the current evidence does not confirm CGRP as an acute-phase therapeutic target for pediatric and adolescent migraine, necessitating validation through higher-quality studies.</p> </section> <section> <h3> Trial Registration</h3> <
背景和目的虽然降钙素基因相关肽（CGRP）已成为偏头痛治疗中有希望的治疗靶点，但目前关于其在儿科偏头痛人群中的动态变化的临床证据仍不确定。我们进行了一项荟萃分析，探讨血液CGRP水平与儿科偏头痛之间的关系。我们系统地检索了PubMed、Web of Science和Embase电子数据库中发表的英文报告儿科偏头痛CGRP水平的观察性研究，或中国国家知识基础设施和万方医学数据库中的中文报告。采用纽卡斯尔-渥太华质量评估量表评估纳入研究的质量。每个结果的证据质量根据推荐分级、评估、发展和评估指南进行评估。结果纳入的1134项研究中，有8项符合纳入条件。有“中等”水平的证据表明，与对照组相比，偏头痛儿童的CGRP水平显著升高（标准化平均差[SMD] = 1.44, 95% CI 0.61-2.31）。分层分析显示，“低”水平的证据显示，在临界期（SMD = 2.39, 95% CI 0.59-4.19）和间歇期（SMD = 1.27, 95% CI 0.54-1.99）的水平都较高。“非常低”质量的证据支持先兆儿童偏头痛患者（SMD = 1.47, 95% CI 0.67-2.27）和无先兆儿童偏头痛患者（SMD = 1.11, 95% CI 0.50-1.72）的CGRP水平高于非偏头痛对照组。结论CGRP水平可能是儿童偏头痛的潜在诊断生物标志物和预防性治疗靶点，但需要高质量的纵向研究来验证。本系统综述和荟萃分析提供了重要证据，证明CGRP水平可作为儿童和青少年偏头痛的潜在诊断生物标志物。未来的研究应进一步探讨CGRP水平对该人群的诊断价值。然而，目前的证据并不能证实CGRP是儿童和青少年偏头痛的急性期治疗靶点，需要通过更高质量的研究进行验证。试验注册号：CRD42025635332
{"title":"Calcitonin Gene-Related Peptide (CGRP) Levels of Children and Adolescents With Migraine: A Systematic Review and Meta-Analysis of Observational Studies","authors":"Guoliang Zhu, Guifang Yan, Ying Luo, Juan Luo","doi":"10.1002/ejp.70177","DOIUrl":"https://doi.org/10.1002/ejp.70177","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective</h3>\u0000 \u0000 <p>Although calcitonin gene-related peptide (CGRP) has emerged as a promising therapeutic target in migraine management, current clinical evidence regarding its dynamic variations in paediatric migraine populations remains inconclusive. We conducted a meta-analysis to explore the relationship between blood CGRP levels and paediatric migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Databases and Data Treatment</h3>\u0000 \u0000 <p>We systematically searched for observational studies that reported CGRP levels in paediatric migraine published in English from the PubMed, Web of Science, and Embase electronic databases, or in Chinese from the Chinese National Knowledge Infrastructure and the WanFang Med database. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The quality of evidence for each outcome was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 1134 identified studies, eight were eligible for inclusion. There was a ‘Moderate’ level of evidence demonstrating significantly elevated CGRP levels in children with migraine compared to controls (standardised mean difference [SMD] = 1.44, 95% CI 0.61–2.31). Stratification analysis showed the ‘Low’ level of evidence revealed higher levels during both ictal (SMD = 2.39, 95% CI 0.59–4.19) and interictal phases (SMD = 1.27, 95% CI 0.54–1.99). ‘Very low’ quality of evidence supported paediatric migraine patients with (SMD = 1.47, 95% CI 0.67–2.27) and without (SMD = 1.11, 95% CI 0.50–1.72) aura had higher CGRP levels than non-migraine controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that CGRP levels may be a potential diagnostic biomarker and prophylactic therapeutic target for paediatric migraine, but need high-quality longitudinal studies to validate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This systematic review and meta-analysis provides significant evidence that CGRP levels serve as a potential diagnostic biomarker for migraine in children and adolescents. Future research should further explore the diagnostic value of CGRP levels in this population. However, the current evidence does not confirm CGRP as an acute-phase therapeutic target for pediatric and adolescent migraine, necessitating validation through higher-quality studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619212","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}
Elise Cnockaert, Kirsty Musch, Stefan Elbers, Albère Köke, Jessica Van Oosterwijck, Ivan Huijnen, Rob Smeets
<div> <section> <h3> Background and Objectives</h3> <p>Interdisciplinary Multimodal Pain Treatment (IMPT), grounded in the biopsychosocial model, is strongly recommended for patients with chronic primary pain. A base review found that IMPT participation leads to sustained improvements in wellbeing, but substantial heterogeneity in program dose and content limited conclusions about optimal design. This first update as a living systematic review (LSR) aimed to assess the long-term effects (≥ 12 months post-treatment) of IMPT for chronic primary musculoskeletal pain and explore patterns in treatment effectiveness to inform program optimization.</p> </section> <section> <h3> Databases and Data Treatment</h3> <p>This LSR updated the base review's systematic search (January 2025) in Medline, Embase, PsycInfo and Cinahl. Eligible studies included adults with chronic primary musculoskeletal pain who completed IMPT and were followed for at least 12 months. Two reviewers independently screened studies, extracted data and assessed risk of bias. Standardised mean changes were calculated for nine outcome domains plus health-related quality of life (HRQoL). Exploratory subgroup analyses examined intervention-specific factors.</p> </section> <section> <h3> Results</h3> <p>Eighty-nine articles (110 cohorts) were included. Significant pre- to post-treatment improvements occurred in 83% of cohorts and were generally maintained at follow-up. HRQoL, newly analysed, improved in 86% of 30 reporting cohorts. Substantial to high heterogeneity (<i>I</i><sup>2</sup> > 61.42%) reflected differences in program design. Exploratory findings suggest that individual formats, using high tailoring and limiting treatment to ≤ 30 contact hours may yield the most consistent benefits.</p> </section> <section> <h3> Conclusions</h3> <p>IMPT programs provide durable improvements in physical, emotional and social functioning, among which HRQoL, though the evidence remains of very low certainty and program variability persists.</p> </section> <section> <h3> Significance</h3> <p>This LSR reaffirms the effectiveness of IMPT in improving physical and psychological outcomes in individuals with chronic primary pain, and expands the evidence base by incorporating HRQoL as a novel outcome. HRQoL improvement underscores the long-term effectiveness of IMPT in improving overall well-being. Highly tailored, individually delivered IMPT programs that integrate recent innovations and are under 30 h in
{"title":"Longitudinal Outcome Evaluations of Interdisciplinary Multimodal Pain Treatment Programs for Patients With Chronic Primary Musculoskeletal Pain: A Living Systematic Review","authors":"Elise Cnockaert, Kirsty Musch, Stefan Elbers, Albère Köke, Jessica Van Oosterwijck, Ivan Huijnen, Rob Smeets","doi":"10.1002/ejp.70174","DOIUrl":"https://doi.org/10.1002/ejp.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Interdisciplinary Multimodal Pain Treatment (IMPT), grounded in the biopsychosocial model, is strongly recommended for patients with chronic primary pain. A base review found that IMPT participation leads to sustained improvements in wellbeing, but substantial heterogeneity in program dose and content limited conclusions about optimal design. This first update as a living systematic review (LSR) aimed to assess the long-term effects (≥ 12 months post-treatment) of IMPT for chronic primary musculoskeletal pain and explore patterns in treatment effectiveness to inform program optimization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Databases and Data Treatment</h3>\u0000 \u0000 <p>This LSR updated the base review's systematic search (January 2025) in Medline, Embase, PsycInfo and Cinahl. Eligible studies included adults with chronic primary musculoskeletal pain who completed IMPT and were followed for at least 12 months. Two reviewers independently screened studies, extracted data and assessed risk of bias. Standardised mean changes were calculated for nine outcome domains plus health-related quality of life (HRQoL). Exploratory subgroup analyses examined intervention-specific factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-nine articles (110 cohorts) were included. Significant pre- to post-treatment improvements occurred in 83% of cohorts and were generally maintained at follow-up. HRQoL, newly analysed, improved in 86% of 30 reporting cohorts. Substantial to high heterogeneity (<i>I</i><sup>2</sup> > 61.42%) reflected differences in program design. Exploratory findings suggest that individual formats, using high tailoring and limiting treatment to ≤ 30 contact hours may yield the most consistent benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IMPT programs provide durable improvements in physical, emotional and social functioning, among which HRQoL, though the evidence remains of very low certainty and program variability persists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This LSR reaffirms the effectiveness of IMPT in improving physical and psychological outcomes in individuals with chronic primary pain, and expands the evidence base by incorporating HRQoL as a novel outcome. HRQoL improvement underscores the long-term effectiveness of IMPT in improving overall well-being. Highly tailored, individually delivered IMPT programs that integrate recent innovations and are under 30 h in","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619213","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}
Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain is defined as ‘pain that arises from altered nociception’ not fully explained by nociceptive or neuropathic pain mechanisms.
Methods
We summarise and extend some discussions of a main session on nociplastic pain at the conference of the European Pain Federation EFIC in Lyon at the 26th April, 2025.
Results
We recommend not to mix up concepts and terms: Nociplastic pain is not synonymous with chronic primary pain nor with central sensitization. Nociplastic pain is not a new term for pain of unknown origin. We identified these controversies: ‘Nociplastic’ might not be the best term. Other specialties (e.g., internal medicine) use different terms and concepts for clinical conditions termed as ‘nociplastic pain conditions’ by pain medicine. Fibromyalgia syndrome is not always the prototype of a pure nociplastic pain condition. ‘Nociplasticity’ can be a continuous (and not a separate) component of pain; hence the requirement to ‘exclude’ nociceptive and neuropathic pain to diagnose nociplastic pain has been questioned.
Conclusions
Future tasks include additional field testing and eventual modification of the criteria for nociplastic pain; development of pharmacological and psychological treatment guidelines, based on the three pain types; unravelling pathophysiological mechanisms driving altered nociception in pain conditions with substantial nociplastic components; development of umbrella concepts unifying the different views of somatic medicine, psychosocial medicine and pain medicine.
Significance Statement
The concept of nociplastic pain has gained growing importance in pain medicine and has been introduced into other specialties such as gynaecology and rheumatology. Clinicians should always strive to identify the major pain mechanisms to guide treatment.
{"title":"Nociplastic Pain: Facts, Controversies and Future Tasks","authors":"Winfried Häuser, Eva Kosek","doi":"10.1002/ejp.70175","DOIUrl":"10.1002/ejp.70175","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain is defined as ‘pain that arises from altered nociception’ not fully explained by nociceptive or neuropathic pain mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We summarise and extend some discussions of a main session on nociplastic pain at the conference of the European Pain Federation EFIC in Lyon at the 26th April, 2025.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We recommend not to mix up concepts and terms: Nociplastic pain is not synonymous with chronic primary pain nor with central sensitization. Nociplastic pain is not a new term for pain of unknown origin. We identified these controversies: ‘Nociplastic’ might not be the best term. Other specialties (e.g., internal medicine) use different terms and concepts for clinical conditions termed as ‘nociplastic pain conditions’ by pain medicine. Fibromyalgia syndrome is not always the prototype of a pure nociplastic pain condition. ‘Nociplasticity’ can be a continuous (and not a separate) component of pain; hence the requirement to ‘exclude’ nociceptive and neuropathic pain to diagnose nociplastic pain has been questioned.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Future tasks include additional field testing and eventual modification of the criteria for nociplastic pain; development of pharmacological and psychological treatment guidelines, based on the three pain types; unravelling pathophysiological mechanisms driving altered nociception in pain conditions with substantial nociplastic components; development of umbrella concepts unifying the different views of somatic medicine, psychosocial medicine and pain medicine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>The concept of nociplastic pain has gained growing importance in pain medicine and has been introduced into other specialties such as gynaecology and rheumatology. Clinicians should always strive to identify the major pain mechanisms to guide treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603334","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}
Rein F. van Welie, Floor C. van Welie, Jennifer P. Trouerbach-Kraan, Albert Dahan, Monique van Velzen, Gisela M. Terwindt
<div> <section> <h3> Background</h3> <p>Migraine pain profiling studies vary by sensory modalities, methods, anatomical sites and characteristics. This exploratory study aimed to identify pain profiling parameters using quantitative sensory testing (QST) for episodic migraine (EM) and chronic migraine (CM) and investigate potential differences, given conflicting results from previous EM versus CM comparisons.</p> </section> <section> <h3> Methods</h3> <p>A total of 59 migraineurs, including 29 with EM and 30 with CM, were enrolled at Leiden Headache Center. QST was performed on the cheek and hand utilising various test stimuli. Normalised control values adjusted for sex, age, location were used to convert the measurement outcomes to Z-scores. Key outcomes included mean Z-scores and the prevalence of abnormal Z-scores (< −1.96 or > 1.96) in migraineurs. Z-scores > 1.96 indicate heightened sensation (lower threshold), while Z-scores < −1.96 indicate diminished sensation (higher threshold). EM and CM were compared.</p> </section> <section> <h3> Results</h3> <p>The threshold for pressure pain (PPT) was lower in 39.0% (hand) and 32.8% (cheek) (all <i>p</i> < 0.001) in individuals with migraine. Cold detection threshold (CDT) was higher in 18.6% (hand) and 25.4% (cheek), while the warm detection threshold (WDT) was higher in 15.2% (hand) (all <i>p</i> < 0.001) in migraineurs. Mechanical pain sensitivity (MPS) was increased in 17.0% (hand) and the vibration detection threshold (VDT) was higher in 18.6% (cheek) (all <i>p</i> < 0.001). No differences, including for temporal summation (TS), were found between EM and CM.</p> </section> <section> <h3> Conclusions</h3> <p>In this exploratory analysis, no QST profile differences were found between EM and CM. One-third of migraineurs have increased pressure pain sensitivity in both trigeminal and distal regions, but decreased cold, warmth, vibration and mechanical detection, indicating complex sensory processing.</p> </section> <section> <h3> Significance</h3> <p>This is the first exploratory study to compare episodic migraine (EM) and chronic migraine (CM) patients using a comprehensive battery of quantitative sensory tests (QST). The aim of this study was to explore various aspects of somatosensory function in individuals with EM and CM, with a particular focus on identifying differences between the two groups. Given that sensory thresholds may fluctuate at different stages of the disease,
{"title":"Exploratory Pain Profiling With Quantitative Sensory Testing (QST) in Episodic and Chronic Migraine","authors":"Rein F. van Welie, Floor C. van Welie, Jennifer P. Trouerbach-Kraan, Albert Dahan, Monique van Velzen, Gisela M. Terwindt","doi":"10.1002/ejp.70171","DOIUrl":"https://doi.org/10.1002/ejp.70171","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Migraine pain profiling studies vary by sensory modalities, methods, anatomical sites and characteristics. This exploratory study aimed to identify pain profiling parameters using quantitative sensory testing (QST) for episodic migraine (EM) and chronic migraine (CM) and investigate potential differences, given conflicting results from previous EM versus CM comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 59 migraineurs, including 29 with EM and 30 with CM, were enrolled at Leiden Headache Center. QST was performed on the cheek and hand utilising various test stimuli. Normalised control values adjusted for sex, age, location were used to convert the measurement outcomes to Z-scores. Key outcomes included mean Z-scores and the prevalence of abnormal Z-scores (< −1.96 or > 1.96) in migraineurs. Z-scores > 1.96 indicate heightened sensation (lower threshold), while Z-scores < −1.96 indicate diminished sensation (higher threshold). EM and CM were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The threshold for pressure pain (PPT) was lower in 39.0% (hand) and 32.8% (cheek) (all <i>p</i> < 0.001) in individuals with migraine. Cold detection threshold (CDT) was higher in 18.6% (hand) and 25.4% (cheek), while the warm detection threshold (WDT) was higher in 15.2% (hand) (all <i>p</i> < 0.001) in migraineurs. Mechanical pain sensitivity (MPS) was increased in 17.0% (hand) and the vibration detection threshold (VDT) was higher in 18.6% (cheek) (all <i>p</i> < 0.001). No differences, including for temporal summation (TS), were found between EM and CM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this exploratory analysis, no QST profile differences were found between EM and CM. One-third of migraineurs have increased pressure pain sensitivity in both trigeminal and distal regions, but decreased cold, warmth, vibration and mechanical detection, indicating complex sensory processing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This is the first exploratory study to compare episodic migraine (EM) and chronic migraine (CM) patients using a comprehensive battery of quantitative sensory tests (QST). The aim of this study was to explore various aspects of somatosensory function in individuals with EM and CM, with a particular focus on identifying differences between the two groups. Given that sensory thresholds may fluctuate at different stages of the disease, ","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538055","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}
Melissa L. Flury, Martin Löffler, Shaili Gour, Susanne Becker
<div> <section> <h3> Background</h3> <p>The experience of pain consists of different components, including sensory-discriminative and emotional-motivational components. While these components are often well aligned, they can also dissociate. Operant conditioning may selectively modulate one component without affecting the other. However, evidence directly comparing operant conditioning effects on both emotional-motivational and sensory-discriminative components of pain is lacking. The aim of the present study was to test whether operant conditioning would differentially affect behavioral surrogate measures of emotional-motivational and sensory-discriminative pain responses.</p> </section> <section> <h3> Methods</h3> <p>62 healthy participants performed in two testing sessions a pain avoidance task to assess emotional-motivational pain responses and a temperature discrimination task to assess sensory-discriminative pain responses (counterbalanced order). In the second half of each task, successful pain avoidance or accurate temperature discrimination was followed by monetary reinforcement.</p> </section> <section> <h3> Results</h3> <p>Contingent reinforcement selectively enhanced pain avoidance, evidenced by faster reaction times and increased success rates, while temperature discrimination performance remained unchanged, likely due to a ceiling effect in task difficulty. Operantly conditioned changes in pain behaviour did not generalize to self-reported pain intensity and unpleasantness ratings.</p> </section> <section> <h3> Conclusions</h3> <p>These findings indicate a modulation of emotional–motivational pain processing by operant conditioning, while effects on sensory–discriminative processing remain absent. These results support the idea that enhanced pain perception in chronic pain can be induced by operant learning, potentially through the specific learning of increased emotional–motivational pain responses.</p> </section> <section> <h3> Significance Statement</h3> <p>This study demonstrates that operant conditioning can enhance avoidance responses, serving as an indicator of emotional–motivational pain responses. In contrast, sensory–discriminative aspects of pain were not modulated by operant conditioning. These results confirm the important role of operant conditioning specifically in emotional–motivational pain processing. This insight may help explain how learning contributes to increased emotional–motivational pain processing in chronic
{"title":"Differential Operant Conditioning of Emotional-Motivational and Sensory-Discriminative Pain Responses","authors":"Melissa L. Flury, Martin Löffler, Shaili Gour, Susanne Becker","doi":"10.1002/ejp.70162","DOIUrl":"10.1002/ejp.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The experience of pain consists of different components, including sensory-discriminative and emotional-motivational components. While these components are often well aligned, they can also dissociate. Operant conditioning may selectively modulate one component without affecting the other. However, evidence directly comparing operant conditioning effects on both emotional-motivational and sensory-discriminative components of pain is lacking. The aim of the present study was to test whether operant conditioning would differentially affect behavioral surrogate measures of emotional-motivational and sensory-discriminative pain responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>62 healthy participants performed in two testing sessions a pain avoidance task to assess emotional-motivational pain responses and a temperature discrimination task to assess sensory-discriminative pain responses (counterbalanced order). In the second half of each task, successful pain avoidance or accurate temperature discrimination was followed by monetary reinforcement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Contingent reinforcement selectively enhanced pain avoidance, evidenced by faster reaction times and increased success rates, while temperature discrimination performance remained unchanged, likely due to a ceiling effect in task difficulty. Operantly conditioned changes in pain behaviour did not generalize to self-reported pain intensity and unpleasantness ratings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings indicate a modulation of emotional–motivational pain processing by operant conditioning, while effects on sensory–discriminative processing remain absent. These results support the idea that enhanced pain perception in chronic pain can be induced by operant learning, potentially through the specific learning of increased emotional–motivational pain responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This study demonstrates that operant conditioning can enhance avoidance responses, serving as an indicator of emotional–motivational pain responses. In contrast, sensory–discriminative aspects of pain were not modulated by operant conditioning. These results confirm the important role of operant conditioning specifically in emotional–motivational pain processing. This insight may help explain how learning contributes to increased emotional–motivational pain processing in chronic","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12630449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556552","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}
Sandra Rierola-Fochs, Marc Terradas-Monllor, Sergi Grau-Carrión, Mirari Ochandorena-Acha, Eduard Minobes-Molina, Jose Antonio Merchán-Baeza
<div> <section> <h3> Background</h3> <p>Phantom limb pain (PLP) affects 64% of individuals who have undergone amputation. Various theories explain its development, leading to different treatments, including graded motor imagery. This study analyses the effectiveness of a home-based intervention protocol based on graded motor imagery (GraMI protocol) as a treatment for phantom limb pain.</p> </section> <section> <h3> Methods</h3> <p>A randomised, controlled, home-based, assessor-blinded clinical trial was conducted on individuals over 18 years old, with limb amputation, pharmacologically stable and discharged home. Participants followed the GraMI protocol or continued their current treatment for 9 weeks. Assessments were conducted at baseline, postintervention and at 3 months follow-up, evaluating PLP, quality of life, functionality and depressive symptoms.</p> </section> <section> <h3> Results</h3> <p>The study enrolled 36 participants (mean age of 58.5 years), including 27 individuals with lower limb amputation and nine with upper limb amputation. Vascular issues were the primary cause, and 17 participants experienced preamputation pain. None of the participants in the control group received any PLP treatment during the study. Compliance with treatment among participants in the experimental group during the laterality recognition and explicit motor imagery phases was satisfactory, averaging 91.4%. Significant differences were found between groups in PLP (<i>p</i> = 0.02), persisting 12 weeks postintervention (<i>p</i> = 0.05). Within-group analysis revealed clinically significant PLP improvements postintervention (<i>p</i> = 0.003), and these improvements remained statistically significant 12 weeks later (<i>p</i> = 0.006). There were no statistically significant differences observed in the rest of the variables.</p> </section> <section> <h3> Conclusion</h3> <p>The GraMI protocol shows effectiveness in reducing PLP in individuals who have undergone amputation, with this effect persisting 12 weeks after the intervention.</p> </section> <section> <h3> Significance Statement</h3> <p>Phantom limb pain significantly impacts individuals with amputations, yet effective treatments remain limited. This study is crucial as it evaluates a home-based graded motor imagery (GraMI) protocol, offering a noninvasive, accessible intervention. The randomised clinical trial demonstrates GraMI's effectiveness in reducing PLP, with lasting effects up to 12 weeks. By ad
{"title":"Graded Motor Imagery (GRAMI Protocol) for Phantom Limb Pain: A Randomised Clinical Trial of Home-Based Intervention","authors":"Sandra Rierola-Fochs, Marc Terradas-Monllor, Sergi Grau-Carrión, Mirari Ochandorena-Acha, Eduard Minobes-Molina, Jose Antonio Merchán-Baeza","doi":"10.1002/ejp.70167","DOIUrl":"https://doi.org/10.1002/ejp.70167","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Phantom limb pain (PLP) affects 64% of individuals who have undergone amputation. Various theories explain its development, leading to different treatments, including graded motor imagery. This study analyses the effectiveness of a home-based intervention protocol based on graded motor imagery (GraMI protocol) as a treatment for phantom limb pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A randomised, controlled, home-based, assessor-blinded clinical trial was conducted on individuals over 18 years old, with limb amputation, pharmacologically stable and discharged home. Participants followed the GraMI protocol or continued their current treatment for 9 weeks. Assessments were conducted at baseline, postintervention and at 3 months follow-up, evaluating PLP, quality of life, functionality and depressive symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study enrolled 36 participants (mean age of 58.5 years), including 27 individuals with lower limb amputation and nine with upper limb amputation. Vascular issues were the primary cause, and 17 participants experienced preamputation pain. None of the participants in the control group received any PLP treatment during the study. Compliance with treatment among participants in the experimental group during the laterality recognition and explicit motor imagery phases was satisfactory, averaging 91.4%. Significant differences were found between groups in PLP (<i>p</i> = 0.02), persisting 12 weeks postintervention (<i>p</i> = 0.05). Within-group analysis revealed clinically significant PLP improvements postintervention (<i>p</i> = 0.003), and these improvements remained statistically significant 12 weeks later (<i>p</i> = 0.006). There were no statistically significant differences observed in the rest of the variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The GraMI protocol shows effectiveness in reducing PLP in individuals who have undergone amputation, with this effect persisting 12 weeks after the intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Phantom limb pain significantly impacts individuals with amputations, yet effective treatments remain limited. This study is crucial as it evaluates a home-based graded motor imagery (GraMI) protocol, offering a noninvasive, accessible intervention. The randomised clinical trial demonstrates GraMI's effectiveness in reducing PLP, with lasting effects up to 12 weeks. By ad","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145537970","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}
Marilena M. DeMayo, Clifford M. Cassidy, Cheryl McCreary, Tuan Trang, Ashley D. Harris, Alexander McGirr
<div> <section> <h3> Background</h3> <p>Fibromyalgia is a chronic pain condition without an established aetiology. However, noradrenergic dysfunction is a possible mechanism to explain the constellation of symptoms associated with fibromyalgia. Noradrenaline synthesis in the locus coeruleus (LC) results in a paramagnetic by-product, neuromelanin. Recently, a magnetic resonance imaging sequence sensitive to neuromelanin has been used to assay LC signal intensity, a proxy for noradrenergic system function. Here, we use MR imaging to investigate the noradrenergic-locus coeruleus system in participants with fibromyalgia and healthy controls.</p> </section> <section> <h3> Methods</h3> <p>Forty-six participants with fibromyalgia and 41 healthy controls were recruited for a cross-sectional characterisation of LC signal intensity at 3 T, quantified from a 2D gradient echo acquisition. Participants completed the Revised Fibromyalgia Impact Questionnaire, as well as measures of anxiety, depression, sleep and the THINC-it cognitive battery.</p> </section> <section> <h3> Results</h3> <p>An independent groups <i>t</i>-test revealed no differences in LC signal intensity between participants with fibromyalgia and healthy controls. For the participants with fibromyalgia, partial correlations accounting for age showed no association between LC signal intensity and fibromyalgia history, fibromyalgia symptom severity, anxiety, depression, insomnia or cognitive performance. Almost 90% of participants with fibromyalgia had been exposed to medications targeting noradrenergic function complicating the interpretation of these findings.</p> </section> <section> <h3> Conclusions</h3> <p>LC signal intensity as measured by MR did not distinguish participants with fibromyalgia and healthy controls, nor was it associated with core fibromyalgia pain symptoms or associated symptoms. Dynamic measures of noradrenergic function may be required to understand noradrenergic contributions to fibromyalgia.</p> </section> <section> <h3> Significance Statement</h3> <p>This study is the first report using MR measured signal intensity of the LC to examine noradrenergic function in participants with fibromyalgia. There was no difference in signal intensity when comparing patients to controls, nor did it associate with any symptoms or associated features of fibromyalgia. This suggests that lifetime noradrenergic function may not distinguish fibromyalgia.</p> </section>
{"title":"Locus Coeruleus MR Measured Signal Intensity in Fibromyalgia Relative to Healthy Controls","authors":"Marilena M. DeMayo, Clifford M. Cassidy, Cheryl McCreary, Tuan Trang, Ashley D. Harris, Alexander McGirr","doi":"10.1002/ejp.70173","DOIUrl":"10.1002/ejp.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fibromyalgia is a chronic pain condition without an established aetiology. However, noradrenergic dysfunction is a possible mechanism to explain the constellation of symptoms associated with fibromyalgia. Noradrenaline synthesis in the locus coeruleus (LC) results in a paramagnetic by-product, neuromelanin. Recently, a magnetic resonance imaging sequence sensitive to neuromelanin has been used to assay LC signal intensity, a proxy for noradrenergic system function. Here, we use MR imaging to investigate the noradrenergic-locus coeruleus system in participants with fibromyalgia and healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-six participants with fibromyalgia and 41 healthy controls were recruited for a cross-sectional characterisation of LC signal intensity at 3 T, quantified from a 2D gradient echo acquisition. Participants completed the Revised Fibromyalgia Impact Questionnaire, as well as measures of anxiety, depression, sleep and the THINC-it cognitive battery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An independent groups <i>t</i>-test revealed no differences in LC signal intensity between participants with fibromyalgia and healthy controls. For the participants with fibromyalgia, partial correlations accounting for age showed no association between LC signal intensity and fibromyalgia history, fibromyalgia symptom severity, anxiety, depression, insomnia or cognitive performance. Almost 90% of participants with fibromyalgia had been exposed to medications targeting noradrenergic function complicating the interpretation of these findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LC signal intensity as measured by MR did not distinguish participants with fibromyalgia and healthy controls, nor was it associated with core fibromyalgia pain symptoms or associated symptoms. Dynamic measures of noradrenergic function may be required to understand noradrenergic contributions to fibromyalgia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This study is the first report using MR measured signal intensity of the LC to examine noradrenergic function in participants with fibromyalgia. There was no difference in signal intensity when comparing patients to controls, nor did it associate with any symptoms or associated features of fibromyalgia. This suggests that lifetime noradrenergic function may not distinguish fibromyalgia.</p>\u0000 </section>\u0000 ","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12621157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534230","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}
Simon F. Zerth, Christian Volberg, Ann-Kristin Schubert, Vanessa Ketter, Monika Sadlonova, Frank Euteneuer, Winfried Rief, Stefan Salzmann
Background
Psychological interventions designed to optimise patients' treatment expectations have proven effective in surgical populations. Since these interventions are often resource-intensive, their clinical application is limited. We aimed to optimise treatment expectations in patients undergoing elective orthopaedic surgery with a brief video-based expectation-focused intervention. Additionally, the role of violated expectations was investigated exploratively.
Methods
In a three-arm randomised clinical trial, participants (N = 125) scheduled to undergo elective orthopaedic surgery received either an expectation-focused video intervention aiming at fostering realistically positive treatment expectations, an active control video or standard medical care. The primary outcome was pain intensity. Measurements were taken at baseline as well as on postoperative days one and seven.
Results
The intervention group reported increased treatment expectations compared to the standard medical care and the control group. No significant intervention effect on pain intensity was found. Patients indicating negative postsurgical expectation violation (feeling worse than expected) reported higher pain intensity, regardless of the study condition. No differences in pain intensity were found between patients, indicating positive or no expectation violation (feeling better or exactly as expected respectively).
Conclusions
Patients' treatment expectations can be optimised with a brief video-based intervention. However, the clinical relevance of this effect may be questionable. Postoperative pain intensity differed by expectation violation profiles. Avoiding a negative expectation violation might be a promising approach for expectation-focused interventions in surgical populations.
Significance
Our findings suggest that treatment expectations can be improved through a brief video-based intervention, though this did not translate into improved postoperative outcomes. These results underscore both the potential and the limitations of very brief expectation-focused approaches and can inform the refinement of such interventions.
{"title":"Optimising Treatment Expectations Using a Video-Based Intervention in Orthopaedic Surgery: Results From a Randomised Controlled Trial","authors":"Simon F. Zerth, Christian Volberg, Ann-Kristin Schubert, Vanessa Ketter, Monika Sadlonova, Frank Euteneuer, Winfried Rief, Stefan Salzmann","doi":"10.1002/ejp.70169","DOIUrl":"https://doi.org/10.1002/ejp.70169","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Psychological interventions designed to optimise patients' treatment expectations have proven effective in surgical populations. Since these interventions are often resource-intensive, their clinical application is limited. We aimed to optimise treatment expectations in patients undergoing elective orthopaedic surgery with a brief video-based expectation-focused intervention. Additionally, the role of violated expectations was investigated exploratively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a three-arm randomised clinical trial, participants (<i>N</i> = 125) scheduled to undergo elective orthopaedic surgery received either an expectation-focused video intervention aiming at fostering realistically positive treatment expectations, an active control video or standard medical care. The primary outcome was pain intensity. Measurements were taken at baseline as well as on postoperative days one and seven.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The intervention group reported increased treatment expectations compared to the standard medical care and the control group. No significant intervention effect on pain intensity was found. Patients indicating negative postsurgical expectation violation (feeling worse than expected) reported higher pain intensity, regardless of the study condition. No differences in pain intensity were found between patients, indicating positive or no expectation violation (feeling better or exactly as expected respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients' treatment expectations can be optimised with a brief video-based intervention. However, the clinical relevance of this effect may be questionable. Postoperative pain intensity differed by expectation violation profiles. Avoiding a negative expectation violation might be a promising approach for expectation-focused interventions in surgical populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Our findings suggest that treatment expectations can be improved through a brief video-based intervention, though this did not translate into improved postoperative outcomes. These results underscore both the potential and the limitations of very brief expectation-focused approaches and can inform the refinement of such interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Ger","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"29 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejp.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522047","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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