PAIN®最新文献

{"title":"Impaired skin reinnervation in Epidermolysis Bullosa due to neurotrophic deficiency.","authors":"Paula Diaz, Mosab Ali Awadelkareem, Daniela Muñoz, Fernanda Espinoza, Alex J Clark, Fernando Altermatt, Loreto Veliz, Amaro S Mora, Alexander Nyström, Ignacia Fuentes, David Bennett, Margarita Calvo","doi":"10.1097/j.pain.0000000000004001","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000004001","url":null,"abstract":"<p><strong>Abstract: </strong>The skin is densely innervated by peripheral sensory neurons that detect various stimuli through specialized nerve endings in the dermis and epidermis. In recessive dystrophic epidermolysis bullosa (RDEB), repeated skin injury disrupts epidermal nerve fibers, leading to neuropathic pain and reduced thermal sensitivity. Normally, keratinocyte-derived neurotrophic signals guide sensory fiber re-entry into healed epidermis. We hypothesized that impaired neurotrophic support underlies failed reinnervation in RDEB. To investigate the mechanisms behind failed reinnervation, we assessed neurotrophic factor expression in a human skin wound model. We analyzed the secretome of primary keratinocytes from healthy donors and patients with RDEB and tested its effects on neurite outgrowth in sensory neurons derived from embryonic rodents and human induced pluripotent stem cells. We also evaluated the regenerative potential of tropomyosin receptor kinase A (TrkA) and glial cell derived neurotrophic factor (GDNF) receptor agonists (gambogic amide and XIB4035) in vitro and in a mouse model of RDEB. In healthy skin, injury triggered robust neurotrophic factor secretion, whereas RDEB skin did not. Secretomes from healthy keratinocytes promoted neurite outgrowth, whereas those from RDEB keratinocytes failed to do so. Receptor agonist treatment restored neurite growth in vitro, enhanced intraepidermal innervation, and reversed thermal hyposensitivity in RDEB mice.These findings suggest that impaired neurotrophic support from RDEB keratinocytes contributes to defective epidermal reinnervation. Pharmacological activation of TrkA and GDNF receptors may offer a therapeutic strategy to restore sensory function and relieve neuropathic pain in RDEB.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of physical activity in children and adolescents with chronic pain: the moderating effects of psychological symptoms and sleep difficulties.","authors":"Guillermo Ceniza-Bordallo, Elisabet Sánchez-Rodríguez, Josep Roman-Juan, Mark P Jensen, Jordi Miró","doi":"10.1097/j.pain.0000000000003997","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003997","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain in children and adolescents affects physical, psychological, social, and academic function. Although physical activity may play a role, its direct effects and its interactions with sleep difficulties and psychological symptoms remain unclear. This cross-sectional study examined whether physical activity is associated with chronic pain, and whether these associations vary by sleep difficulties and psychological symptoms. We analyzed data from 212,105 individuals (49% girls, age: 11-15 years) from the 2018 Health Behavior in School-aged Children study. Chronic pain, psychological symptoms, sleep difficulties, moderate-to-vigorous physical activity (MVPA), and vigorous physical activity (VPA) were assessed using validated self-report measures. Three multivariate logistic regression models (for chronic back pain, stomachache, and headache) examined main and moderation effects, adjusting for age, gender identity, and socioeconomic status. In adjusted main-effects models, higher MVPA was associated with higher odds of chronic back pain (aOR 1.15, 95% CI 1.06-1.25) and stomachache (aOR 1.02, 95% CI 1.00-1.09) but not headache. Interaction models indicated that MVPA associations differed by sleep difficulties, and the VPA-pain association differed by psychological symptoms. In stratified analyses, several MVPA frequency categories (vs 0 d/wk) were associated with lower odds of back pain and stomachache in both low and high sleep-difficulty groups. Vigorous physical activity was associated with lower odds of back pain and stomachache among adolescents with moderate or high psychological symptoms but not those with low symptom frequency. Overall, physical activity was not uniformly protective; associations were pain-type specific and varied according to adolescents sleep and psychological profiles.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and prediction models for pain after endometriosis-related surgery-what do we (not) know yet.","authors":"Esther Miriam Pogatzki-Zahn, Daniel Segelcke, Andrew W Horne","doi":"10.1097/j.pain.0000000000003916","DOIUrl":"10.1097/j.pain.0000000000003916","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"995-997"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endometriosis Pain Index: development of a model to predict poor pain-related quality of life after endometriosis surgery through machine learning analysis of registry data.","authors":"Dwayne R Tucker, Brie Dungate, Derek S Chiu, Heather L Noga, Caroline Lee, Mohamed A Bedaiwy, Christina Williams, Catherine Allaire, Aline Talhouk, Paul J Yong","doi":"10.1097/j.pain.0000000000003915","DOIUrl":"10.1097/j.pain.0000000000003915","url":null,"abstract":"<p><strong>Abstract: </strong>Predictive tools are lacking for pain-related outcomes after endometriosis surgery. The objective of this study was to develop and validate a machine learning-based clinical model to predict poor pain-related quality of life after endometriosis surgery. Registry data from a prospective longitudinal cohort at a tertiary referral center (2013-2020) was used for model development and validation. Participants underwent an index endometriosis surgery, and completed the pain subscale of the Endometriosis Health Profile-30 (EHP-30) at baseline and 1-2-year follow-up. The outcome was poor pain-related quality of life defined as EHP-30 pain subscale above the 75th percentile for North America, at 1 to 2 years postsurgery. Thirty-two preoperative factors were evaluated, with final models retaining the top 10 most important predictors. Elastic net logistic regression, random forest (RF) and multilayer perceptron neural network models were developed. Internal validation was performed using 500 bootstrap samples, and a held-out test cohort. The study included 650 participants: 488 in the training cohort and 162 in a held-out test cohort. The RF model exhibited the most consistent discrimination, measured by the area under the receiver operating characteristic curve, between the training cohort (0.768; 95% CI: 0.690-0.837) and test cohort (0.766; 95% CI: 0.676-0.863, Δ = -0.002). The RF model also demonstrated the best integrated calibration index (0.029) and highest net benefit. Final preoperative predictors for the RF model included baseline EHP-30 score, surgery type (conservative fertility-sparing vs hysterectomy), anxiety scores, depression scores, pain catastrophizing scale scores, abdominal wall pain, pelvic floor myalgia, smoking status, back pain, and race/ethnicity. We present the RF model as the Endometriosis Pain Index to aid preoperative counselling for endometriosis surgery.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1026-1039"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Chen and Yeh.","authors":"Jonathan D Enders, Cheryl Louise Stucky","doi":"10.1097/j.pain.0000000000003887","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003887","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"167 5","pages":"1238-1239"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why can we hurt ourselves? Human agency and embodied action in the attenuation of self-induced pain.","authors":"Shan Wang, Christopher Eccleston, Kate Wilmut, Francis Keefe, Edmund Keogh","doi":"10.1097/j.pain.0000000000003899","DOIUrl":"10.1097/j.pain.0000000000003899","url":null,"abstract":"<p><strong>Abstract: </strong>Self-initiated actions often generate sensory signals perceived to be less intense than identical signals generated externally. This phenomenon, known as sensory attenuation, is particularly robust for nonpainful tactile sensations. For pain, however, even if the stimulation is self-generated and predictable, it remains painful, albeit sometimes slightly less intense. This difference may reflect the functional divergence between pain and nonpainful sensations, with the sense of agency playing a central role in this distinction. Across 2 experiments involving 61 pain-free adults, we investigated the attenuation of self-induced pain and nonpainful sensations across different stimulation modalities, contexts, and agency levels. We found that self-induced attenuation depended on stimulation modality rather than intensity, with significant reductions for modalities involving strong motoric components and high spatiotemporal alignment (eg, mechanical pressure), in line with the internal forward model. Individuals' trait agency played a pivotal role, with stronger agency associated with enhanced attenuation of nonpainful sensations and mild pain, but reduced attenuation of intense pain. Sex differences also emerged with stronger attenuation effects in men, who also reported higher levels of agency. This study is the first to show that trait-level agency differentially modulates attenuation for painful and nonpainful sensations and the first to explore sex differences. By comparing pain with nonpainful touch, we proposed that self-induced sensations are not attenuated uniformly but shaped by evolutionary priorities such that socially or playfully mediated sensations are more readily suppressed, while high-threat sensations like pain resist qualitative suppression to preserve their protective function.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1182-1195"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145864214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pelvic Pain Bias Assessment: a new assessment of interpretation bias specific to pelvic pain.","authors":"Brydee Pickup, Louise Sharpe, Rachel E Menzies, Jemma Todd","doi":"10.1097/j.pain.0000000000003873","DOIUrl":"10.1097/j.pain.0000000000003873","url":null,"abstract":"<p><strong>Abstract: </strong>Pelvic pain is a common and often debilitating experience with limited treatment options. Improving understanding of the psychosocial mechanisms involved in pelvic pain experiences will enhance the efficacy of pain management interventions. Interpretation bias is a promising psychosocial factor in leading models of chronic pain, yet its relevance for pelvic pain remains poorly understood. The current study sought to assess disorder specific interpretation bias in people with endometriosis and other pelvic pain-related conditions. To do so, we developed a new interpretation bias assessment tool based on existing literature and used this to investigate interpretation bias and relationships with pain, menstrual symptoms, and psychological distress across pelvic pain-related conditions. The sample comprised 342 individuals including those with endometriosis, adenomyosis, chronic pelvic pain, polycystic ovarian syndrome, and those without pelvic pain-related conditions. Participants completed an online survey including demographics, new and modified interpretation bias scenarios, pain-related outcomes, and psychological distress. After a rigorous item selection process, 27 ambiguous pelvic pain-related scenarios were retained, forming the Pelvic Pain Bias Assessment (PPBA). Using the PPBA, we replicated our previous finding of elevated interpretation bias among individuals with endometriosis relative to controls and found interpretation bias was also elevated among individuals with other pelvic pain-related conditions relative to controls. Stronger interpretation bias was associated with worse pelvic pain and menstrual symptoms among individuals with and without pelvic pain-related conditions. This study adds to the growing evidence that interpretation bias is associated with a range of pain conditions and poorer pain-related outcomes in pelvic pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1016-1025"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145655214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokines as targets to treat chronic postoperative pain.","authors":"Manu Rangachari, Nader Ghasemlou","doi":"10.1097/j.pain.0000000000003940","DOIUrl":"10.1097/j.pain.0000000000003940","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"998-999"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the impact of nerve injury on locus coeruleus function and behaviour in mice.","authors":"Patricia Mariscal, Adrián Martínez-Cortés, Meritxell Llorca-Torralba, Jone Razquin, Cristina Miguelez, Cristina Ulecia-Morón, Borja García-Bueno, Juan Carlos Leza, Lidia Bravo, Esther Berrocoso","doi":"10.1097/j.pain.0000000000003927","DOIUrl":"10.1097/j.pain.0000000000003927","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain often coexists with anxiety and depression, particularly in women. The locus coeruleus (LC), a noradrenergic nucleus, modulates pain and emotional states and shows sex-specific structural and functional properties in preclinical studies. Moreover, clinical evidence indicates sex differences in the experience of chronic pain and its emotional impact. These findings highlight the need to explore the LC mechanisms underlying sex-dependent differences in chronic pain. In this study, we examined the sex-specific role of the LC in chronic pain and its emotional and cognitive consequences. Male and female mice exposed to the chronic constriction injury (CCI) model (2/3 and 7/11 weeks postinjury) were evaluated for sensory responses (von Frey, acetone, plantar tests), anxiety-like behavior (open field), depressive-like behavior (tail suspension test, forced swimming test), and cognitive performance (novel object recognition test). We also analyzed the number, somatodendritic volume, and electrophysiological properties of noradrenergic LC neurons. Finally, we assessed the effects of chemogenetic LC inhibition on anxiety- and depressive-like behavior, as well as fear responses. Nerve injury induced immediate sensory hypersensitivity in both sexes. Depressive-like behavior and cognitive deficits appeared only after prolonged injury. Notably, anxiety-like behavior and enhanced fear conditioning were exclusive to CCI male mice and correlated with LC-specific changes: increased cell number and somatodendritic volume, as well as heightened excitability. In female mice, however, neuronal excitability was reduced. Chemogenetic LC inhibition reversed anxiety- and depressive-like behaviors and fear responses only in CCI male mice. These findings show that neuropathic pain elicits sex-specific emotional and neural responses in the LC, highlighting the need for sex-specific approaches when investigating LC function and developing targeted interventions.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1072-1083"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conflations confound nociplastic pain.","authors":"Milton L Cohen, John L Quintner, Asaf Weisman","doi":"10.1097/j.pain.0000000000003928","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003928","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"167 5","pages":"1240-1241"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}