Small-scale care providers often encounter challenges in demonstrating the effectiveness of treatments through randomised controlled trials (RCTs) because of the high costs and organisational demands of RCTs. The current study examines the feasibility of evaluating a multidisciplinary treatment for chronic low back pain using a waiting list as a control group.
Material and Methods
Of 344 chronic pain patients referred to a Dutch outpatient rehabilitation clinic, 123 received treatment, while 88 were on a waiting list. The main effect parameters were pain (visual analogue scale), daily limitations (Quebec Back Pain Disability Scale), and fear of motion (Tampa Scale for Kinesiophobia). Data were collected at the beginning of treatment, after 8 weeks, and after 3 months (follow-up), or after another 8 weeks for waitlist patients receiving treatment after the waiting list period.
Results
The intervention group showed significant persistent improvement in relation to pain (54.1 ± 22.0 to 34.8 ± 23.6), daily limitations (45.1 ± 15.3 to 32.9 ± 15.4), and fear of motion (36.5 ± 8.5 to 30.0 ± 7.3). Subsequently, 51 subjects on the waiting list received treatment, with results similar to those of the initial intervention group. Dysfunctional pain coping strategies diminished during therapy.
Discussion
Multidisciplinary rehabilitation was shown to be more effective than being placed on a waiting list, even when participants were receiving other treatments. Small-scale, high-quality effect studies using a waiting list control group may have scientific potential.
Significance
RCT's are considered the gold standard in effect studies; however, due to financial, organisational, and ethical concerns, performing RCT's can be difficult for small-sized care settings that provide multidisciplinary rehabilitation for chronic back pain. As a result, these treatment options often do not receive sufficient scientific or clinical attention. This study demonstrates that alternative methodologically transparent effect studies using a “waiting list” control can be conducted in small-scale clinical settings with limited means.
{"title":"Effectiveness of Multidisciplinary Rehabilitation in Chronic Low Back Pain: A Pragmatic Study With a Waiting List Control Group","authors":"J. P. van Wingerden, T. van Opstal","doi":"10.1002/ejp.70209","DOIUrl":"10.1002/ejp.70209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Small-scale care providers often encounter challenges in demonstrating the effectiveness of treatments through randomised controlled trials (RCTs) because of the high costs and organisational demands of RCTs. The current study examines the feasibility of evaluating a multidisciplinary treatment for chronic low back pain using a waiting list as a control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>Of 344 chronic pain patients referred to a Dutch outpatient rehabilitation clinic, 123 received treatment, while 88 were on a waiting list. The main effect parameters were pain (visual analogue scale), daily limitations (Quebec Back Pain Disability Scale), and fear of motion (Tampa Scale for Kinesiophobia). Data were collected at the beginning of treatment, after 8 weeks, and after 3 months (follow-up), or after another 8 weeks for waitlist patients receiving treatment after the waiting list period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The intervention group showed significant persistent improvement in relation to pain (54.1 ± 22.0 to 34.8 ± 23.6), daily limitations (45.1 ± 15.3 to 32.9 ± 15.4), and fear of motion (36.5 ± 8.5 to 30.0 ± 7.3). Subsequently, 51 subjects on the waiting list received treatment, with results similar to those of the initial intervention group. Dysfunctional pain coping strategies diminished during therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Multidisciplinary rehabilitation was shown to be more effective than being placed on a waiting list, even when participants were receiving other treatments. Small-scale, high-quality effect studies using a waiting list control group may have scientific potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>RCT's are considered the gold standard in effect studies; however, due to financial, organisational, and ethical concerns, performing RCT's can be difficult for small-sized care settings that provide multidisciplinary rehabilitation for chronic back pain. As a result, these treatment options often do not receive sufficient scientific or clinical attention. This study demonstrates that alternative methodologically transparent effect studies using a “waiting list” control can be conducted in small-scale clinical settings with limited means.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manon Sendel, Lena Ehmke, Andreas Dunst, Jan Vollert, Henrike Bruckmüller, Sandra Brügge, Stefanie Rehm, Janne Gierthmühlen, Dilara Kersebaum, Ingolf Cascorbi, Ralf Baron, Julia Forstenpointner
Background
Topical high-dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non-interventional exploratory study was to improve prediction of treatment response to high-dose capsaicin by including quantifiable parameters and standardised questionnaires.
Methods
Forty-eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient-reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser-speckle-contrast-analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO-synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).
Results
Patient-reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.
Conclusion
A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high-dose capsaicin treatment and provide promising targets for future investigation.
Significance Statement
This exploratory study identifies promising predictors for analgesic response to high-concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve-fibre assessments and genetic polymorphisms.
{"title":"Response to High-Dose Topical Capsaicin in Neuropathic Pain: Absence of Deep Pain as a Predictor of Analgesic Effect","authors":"Manon Sendel, Lena Ehmke, Andreas Dunst, Jan Vollert, Henrike Bruckmüller, Sandra Brügge, Stefanie Rehm, Janne Gierthmühlen, Dilara Kersebaum, Ingolf Cascorbi, Ralf Baron, Julia Forstenpointner","doi":"10.1002/ejp.70200","DOIUrl":"10.1002/ejp.70200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Topical high-dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non-interventional exploratory study was to improve prediction of treatment response to high-dose capsaicin by including quantifiable parameters and standardised questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient-reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser-speckle-contrast-analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO-synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient-reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high-dose capsaicin treatment and provide promising targets for future investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>This exploratory study identifies promising predictors for analgesic response to high-concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve-fibre assessments and genetic polymorphisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12785507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuukka Korpela, Jaro Karppinen, Petteri Oura, Markus Paananen, Arnold Y. L. Wong, Ilona Merikanto, Eveliina Heikkala
Background
Musculoskeletal (MSK) pain and insomnia are interrelated and individually linked to reduced health-related quality of life (HRQoL). This study aimed to enlighten the association of concurrent disabling MSK pain and insomnia with HRQoL among middle-aged individuals.
Methods
Members of the Northern Finland Birth Cohort 1966 were surveyed at age 46 years (analytic sample N = 4 130, 56.7% women). Validated Athens insomnia scale was used to determine insomnia status and HRQoL was assessed with the 15D (15-dimensional) questionnaire. Associations between different combinations of disabling MSK pain and insomnia (concurrent, isolated, absent) with HRQoL were analysed using general linear regression, adjusting for sex, smoking, educational level, physical activity and coexisting diseases. Fifteen HRQoL dimensions were also analysed separately.
Results
The prevalence of concurrent disabling MSK pain and insomnia was 14.3%, while 50.8% reported neither condition. Adjusted 15D mean score of participants with concurrent disabling MSK pain and insomnia was significantly lower (beta [β] coefficient: −0.068 [95% CI −0.073 to −0.062]) compared to those without. Concurrent conditions were associated with lower HRQoL than isolated insomnia and isolated disabling MSK pain (β coefficients: −0.032 [95% CI −0.039 to −0.024] and −0.042 [95% CI −0.050 to −0.034], respectively). Fourteen of 15 HRQoL dimensions were the lowest among participants with concurrent conditions.
Conclusions
This study shows that every seventh of the study population has disabling MSK pain and insomnia concurrently and they are more strongly associated with lower HRQoL compared to isolated or absent conditions. The negative effects of comorbid conditions on HRQoL are reflected across multiple dimensions.
Significance Statement
Musculoskeletal pain and insomnia together exert a compounded negative effect on health-related quality of life, highlighting the need for integrated management strategies. Treating pain alone may not be enough and routine sleep assessment could be a critical point.
背景：肌肉骨骼（MSK）疼痛和失眠相互关联，并与健康相关生活质量（HRQoL）降低单独相关。本研究旨在揭示中年人同时致残的MSK疼痛和失眠与HRQoL的关系。方法：对1966年芬兰北部出生队列46岁的成员进行调查（分析样本N = 4130, 56.7%为女性）。采用经验证的雅典失眠症量表评估失眠状况，采用15D（15维）问卷评估HRQoL。使用一般线性回归分析致残性MSK疼痛和失眠（并发、孤立、不存在）的不同组合与HRQoL之间的关系，调整性别、吸烟、教育水平、体育活动和共存疾病。15个HRQoL维度也分别进行了分析。结果：并发致残MSK疼痛和失眠的患病率为14.3%，而50.8%的人没有出现这种情况。与不伴有致残性MSK疼痛和失眠的受试者相比，伴有致残性MSK疼痛和失眠的校正后15D平均评分显著降低（β [β]系数：-0.068 [95% CI -0.073至-0.062]）。与孤立性失眠和孤立性致残性MSK疼痛相比，并发条件与较低的HRQoL相关（β系数分别为-0.032 [95% CI -0.039至-0.024]和-0.042 [95% CI -0.050至-0.034]）。15个HRQoL维度中有14个在并发疾病的参与者中最低。结论：本研究表明，七分之一的研究人群同时患有致残性MSK疼痛和失眠，与孤立或无症状相比，它们与较低的HRQoL相关性更强。合并症对HRQoL的负面影响反映在多个维度上。意义说明：肌肉骨骼疼痛和失眠共同对健康相关的生活质量产生复合的负面影响，突出了综合管理策略的必要性。仅仅治疗疼痛可能是不够的，常规的睡眠评估可能是一个关键点。
{"title":"Musculoskeletal Pain, Insomnia and Health-Related Quality of Life: Associations in the Middle-Aged General Population","authors":"Tuukka Korpela, Jaro Karppinen, Petteri Oura, Markus Paananen, Arnold Y. L. Wong, Ilona Merikanto, Eveliina Heikkala","doi":"10.1002/ejp.70197","DOIUrl":"10.1002/ejp.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Musculoskeletal (MSK) pain and insomnia are interrelated and individually linked to reduced health-related quality of life (HRQoL). This study aimed to enlighten the association of concurrent disabling MSK pain and insomnia with HRQoL among middle-aged individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Members of the Northern Finland Birth Cohort 1966 were surveyed at age 46 years (analytic sample <i>N</i> = 4 130, 56.7% women). Validated Athens insomnia scale was used to determine insomnia status and HRQoL was assessed with the 15D (15-dimensional) questionnaire. Associations between different combinations of disabling MSK pain and insomnia (concurrent, isolated, absent) with HRQoL were analysed using general linear regression, adjusting for sex, smoking, educational level, physical activity and coexisting diseases. Fifteen HRQoL dimensions were also analysed separately.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of concurrent disabling MSK pain and insomnia was 14.3%, while 50.8% reported neither condition. Adjusted 15D mean score of participants with concurrent disabling MSK pain and insomnia was significantly lower (beta [<i>β</i>] coefficient: −0.068 [95% CI −0.073 to −0.062]) compared to those without. Concurrent conditions were associated with lower HRQoL than isolated insomnia and isolated disabling MSK pain (<i>β</i> coefficients: −0.032 [95% CI −0.039 to −0.024] and −0.042 [95% CI −0.050 to −0.034], respectively). Fourteen of 15 HRQoL dimensions were the lowest among participants with concurrent conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study shows that every seventh of the study population has disabling MSK pain and insomnia concurrently and they are more strongly associated with lower HRQoL compared to isolated or absent conditions. The negative effects of comorbid conditions on HRQoL are reflected across multiple dimensions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Musculoskeletal pain and insomnia together exert a compounded negative effect on health-related quality of life, highlighting the need for integrated management strategies. Treating pain alone may not be enough and routine sleep assessment could be a critical point.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12767138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Mema, Julia A. Glombiewski, Christopher Milde, Ulrike Basten, Julia Karbach, Tanja Könen, Tanja Lischetzke, Lea Schemer
Background
Emotion regulation (ER) is considered a transdiagnostic mechanism underlying chronic pain (CP) and depression in theoretical models such as the Örebro framework. Yet most work has focused on between-person differences rather than within-person dynamics.
Methods
This study examined whether individuals with CP show lower ER success than those without CP (NCP), whether ER or pain regulation (PR) success varies with pain experience and negative emotions at within- and between-person levels, and whether pain duration exacerbates these effects via reduced self-efficacy. Participants included a CP group (n = 176) and an NCP group (n = 161) who completed baseline assessments and a 2-week ambulatory assessment (AA) with five daily surveys.
Results
The CP group had significantly lower ER success than the NCP group (moderate effect: d = −0.48). Within the CP group, ER success decreased with higher-than-usual pain experience (large within-person effect: d = −0.72) and higher overall pain experience (moderate between-person effect: d = −0.55). Similarly, higher-than-usual negative emotions (moderate within-person effect: d = −0.43) and higher overall negative emotions (small between-person effect: d = −0.36) were linked to lower PR success. Pain duration did not moderate the relationship between pain experience and ER success.
Conclusion
Findings align with the Örebro model, suggesting that pain flare-ups and negative mood strain the ER system and contribute to ER difficulties in CP, though long-term processes were not captured by pain duration or self-efficacy.
Significance Statement
By zooming in on within-person dynamics, this study adds to growing research on ER difficulties as a transdiagnostic factor underlying chronic pain and co-occurring emotional problems. Clinically, our findings highlight the potential of just-in-time interventions integrated with ER-focused pain management, offering support at moments of greatest need.
{"title":"Emotion Regulation in Chronic Pain Is Impaired When Pain Is High: Results From a Large Ambulatory Assessment Study","authors":"Christina Mema, Julia A. Glombiewski, Christopher Milde, Ulrike Basten, Julia Karbach, Tanja Könen, Tanja Lischetzke, Lea Schemer","doi":"10.1002/ejp.70204","DOIUrl":"10.1002/ejp.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emotion regulation (ER) is considered a transdiagnostic mechanism underlying chronic pain (CP) and depression in theoretical models such as the Örebro framework. Yet most work has focused on between-person differences rather than within-person dynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study examined whether individuals with CP show lower ER success than those without CP (NCP), whether ER or pain regulation (PR) success varies with pain experience and negative emotions at within- and between-person levels, and whether pain duration exacerbates these effects via reduced self-efficacy. Participants included a CP group (<i>n</i> = 176) and an NCP group (<i>n</i> = 161) who completed baseline assessments and a 2-week ambulatory assessment (AA) with five daily surveys.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CP group had significantly lower ER success than the NCP group (moderate effect: <i>d</i> = −0.48). Within the CP group, ER success decreased with higher-than-usual pain experience (large within-person effect: <i>d</i> = −0.72) and higher overall pain experience (moderate between-person effect: <i>d</i> = −0.55). Similarly, higher-than-usual negative emotions (moderate within-person effect: <i>d</i> = −0.43) and higher overall negative emotions (small between-person effect: <i>d</i> = −0.36) were linked to lower PR success. Pain duration did not moderate the relationship between pain experience and ER success.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Findings align with the Örebro model, suggesting that pain flare-ups and negative mood strain the ER system and contribute to ER difficulties in CP, though long-term processes were not captured by pain duration or self-efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>By zooming in on within-person dynamics, this study adds to growing research on ER difficulties as a transdiagnostic factor underlying chronic pain and co-occurring emotional problems. Clinically, our findings highlight the potential of just-in-time interventions integrated with ER-focused pain management, offering support at moments of greatest need.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonas Eck, Stephan Bigalke, Martin Schmelz, Daniela Constanze Rosenberger, Bruno Pradier, Frank Rutsch, Claudia Sommer, Frank Birklein, Daniel Segelcke, Esther Pogatzki-Zahn
Background
Peripheral neuropathies (PNP) cause a wide range of symptoms of which pruritus and pain are a major burden to patients. Clarifying their mechanisms will facilitate the adequate symptom management. In contrast to neuropathic pain, neuropathic pruritus has long been understudied. We investigate inhibitory pruritus mechanisms in patients with PNP.
Methods
A total of 39 participants (median age: 57 years [27–81], 25♀/14♂), including 16 patients with PNP and pruritus (PNPPRU) and 8 with PNP but without pruritus (PNPNO-PRU), and 15 controls, were enrolled and phenotyped using dynamic and static quantitative sensory testing, determination of intradermal nerve fibre density, and conditioned pain (CPM) and itch (CIM) modulation. For CIM, an electrically induced itch test stimulus (TS) was applied with an individual itch intensity of > 30 NRS (0–100). A cold-water bath (contralateral side) served as the conditioning stimulus (CS). Itch, pain intensity and the desire to scratch upon TS were rated before, during and after the CS was applied.
Results
Using our novel CIM protocol, well-controlled and stable itch was electrically induced in controls and in both PNP groups, regardless of whether or not pruritus was a symptom. Concomitant painful cold stimuli reduced electrically induced itch in all three groups to a similar degree. However, PNPPRU patients had significantly shorter itch inhibition (CIM effects) compared to controls and PNPNO-PRU, whereas CPM effects were not different between groups.
Conclusions
The results show reduced endogenous itch inhibition in patients with chronic itch, which represents a possible mechanism of chronic pruritus in PNP.
Significance Statement
Reduced itch inhibition is associated with the symptom of chronic pruritus in PNP patients, suggesting that reduced descending itch inhibition may facilitate chronic itch in peripheral neuropathy.
{"title":"Reduced Descending Itch Inhibition in Peripheral Neuropathy Patients With Chronic Pruritus","authors":"Jonas Eck, Stephan Bigalke, Martin Schmelz, Daniela Constanze Rosenberger, Bruno Pradier, Frank Rutsch, Claudia Sommer, Frank Birklein, Daniel Segelcke, Esther Pogatzki-Zahn","doi":"10.1002/ejp.70190","DOIUrl":"10.1002/ejp.70190","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Peripheral neuropathies (PNP) cause a wide range of symptoms of which pruritus and pain are a major burden to patients. Clarifying their mechanisms will facilitate the adequate symptom management. In contrast to neuropathic pain, neuropathic pruritus has long been understudied. We investigate inhibitory pruritus mechanisms in patients with PNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 39 participants (median age: 57 years [27–81], 25♀/14♂), including 16 patients with PNP and pruritus (PNP<sub>PRU</sub>) and 8 with PNP but without pruritus (PNP<sub>NO-PRU</sub>), and 15 controls, were enrolled and phenotyped using dynamic and static quantitative sensory testing, determination of intradermal nerve fibre density, and conditioned pain (CPM) and itch (CIM) modulation. For CIM, an electrically induced itch test stimulus (TS) was applied with an individual itch intensity of > 30 NRS (0–100). A cold-water bath (contralateral side) served as the conditioning stimulus (CS). Itch, pain intensity and the desire to scratch upon TS were rated before, during and after the CS was applied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using our novel CIM protocol, well-controlled and stable itch was electrically induced in controls and in both PNP groups, regardless of whether or not pruritus was a symptom. Concomitant painful cold stimuli reduced electrically induced itch in all three groups to a similar degree. However, PNP<sub>PRU</sub> patients had significantly shorter itch inhibition (CIM effects) compared to controls and PNP<sub>NO-PRU</sub>, whereas CPM effects were not different between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results show reduced endogenous itch inhibition in patients with chronic itch, which represents a possible mechanism of chronic pruritus in PNP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Reduced itch inhibition is associated with the symptom of chronic pruritus in PNP patients, suggesting that reduced descending itch inhibition may facilitate chronic itch in peripheral neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Víctor Riquelme-Aguado, María Elena González-Álvarez, Silvia Di-Bonaventura, Leonardo Rodríguez-Lagos, Alazne Zabarte del Campo, Francisco Gómez-Esquer, Gema Díaz-Gil, Antonio Gil-Crujera
<div> <section> <h3> Introduction</h3> <p>Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response.</p> </section> <section> <h3> Objectives</h3> <p>To examine associations between selected genetic polymorphisms and psychological variables in women with FM.</p> </section> <section> <h3> Methods</h3> <p>A cross-sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables—anxiety, depression and catastrophising—were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped (<i>COMT</i> rs4680, <i>DRD3</i> rs6280, <i>OPRM1</i> rs1799971, <i>BDNF</i> rs6265, <i>MAOA</i> rs1137070, <i>FKBP5</i> rs1360780, <i>IL6</i> rs1800796, <i>TNF</i> rs1800629, <i>IL10</i> rs1800896, <i>IFITM3</i> rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal–Wallis with Tukey or Mann–Whitney post hoc tests.</p> </section> <section> <h3> Results</h3> <p>Pain intensity correlated with depression (<i>r</i> = 0.476, <i>p</i> < 0.001), catastrophising (<i>r</i> = 0.414, <i>p</i> < 0.001), and anxiety (<i>r</i> = 0.314, <i>p</i> = 0.009). Catastrophising was related to depression (<i>r</i> = 0.615, <i>p</i> < 0.001), anxiety (<i>r</i> = 0.453, <i>p</i> < 0.001), and kinesiophobia (<i>r</i> = 0.445, <i>p</i> < 0.001). <i>BDNF</i> rs6265 was associated with catastrophising (<i>p</i> = 0.044), <i>OPRM1</i> rs1799971 with anxiety (<i>p</i> = 0.030), and <i>MAOA</i> rs1137070 with depression (<i>p</i> = 0.020).</p> </section> <section> <h3> Conclusions</h3> <p>Psychological variables in FM are interrelated and linked to pain perception. <i>BDNF</i>, <i>OPRM1</i> and <i>MAOA</i> polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM.</p> </section> <section> <h3> Significance Statement</h3> <p>Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psy
{"title":"Associations Between Genetic Polymorphisms and Psychological Variables in Women With Fibromyalgia: A Cross-Sectional Study","authors":"Víctor Riquelme-Aguado, María Elena González-Álvarez, Silvia Di-Bonaventura, Leonardo Rodríguez-Lagos, Alazne Zabarte del Campo, Francisco Gómez-Esquer, Gema Díaz-Gil, Antonio Gil-Crujera","doi":"10.1002/ejp.70201","DOIUrl":"10.1002/ejp.70201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Fibromyalgia (FM) is a multifactorial syndrome involving chronic pain and psychological distress. Psychological traits such as anxiety, depression, and catastrophising are linked to symptom severity. Genetic variability may contribute to these dimensions through mechanisms related to pain modulation and stress response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To examine associations between selected genetic polymorphisms and psychological variables in women with FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study was conducted in 67 women diagnosed with FM. Pain intensity, FM impact and psychological variables—anxiety, depression and catastrophising—were assessed using validated questionnaires. Saliva samples were collected and 10 SNPs were genotyped (<i>COMT</i> rs4680, <i>DRD3</i> rs6280, <i>OPRM1</i> rs1799971, <i>BDNF</i> rs6265, <i>MAOA</i> rs1137070, <i>FKBP5</i> rs1360780, <i>IL6</i> rs1800796, <i>TNF</i> rs1800629, <i>IL10</i> rs1800896, <i>IFITM3</i> rs12252). Correlations were assessed using Pearson or Spearman coefficients, and associations were examined using ANOVA or Kruskal–Wallis with Tukey or Mann–Whitney post hoc tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Pain intensity correlated with depression (<i>r</i> = 0.476, <i>p</i> < 0.001), catastrophising (<i>r</i> = 0.414, <i>p</i> < 0.001), and anxiety (<i>r</i> = 0.314, <i>p</i> = 0.009). Catastrophising was related to depression (<i>r</i> = 0.615, <i>p</i> < 0.001), anxiety (<i>r</i> = 0.453, <i>p</i> < 0.001), and kinesiophobia (<i>r</i> = 0.445, <i>p</i> < 0.001). <i>BDNF</i> rs6265 was associated with catastrophising (<i>p</i> = 0.044), <i>OPRM1</i> rs1799971 with anxiety (<i>p</i> = 0.030), and <i>MAOA</i> rs1137070 with depression (<i>p</i> = 0.020).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Psychological variables in FM are interrelated and linked to pain perception. <i>BDNF</i>, <i>OPRM1</i> and <i>MAOA</i> polymorphisms are associated with indices of psychological vulnerability, underscoring the importance of integrating genetic and psychological perspectives to understand variability in FM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance Statement</h3>\u0000 \u0000 <p>Genetic variability influences psychological vulnerability in fibromyalgia. Specific variants were associated with key psy","PeriodicalId":12021,"journal":{"name":"European Journal of Pain","volume":"30 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145855143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号