PAIN®最新文献

{"title":"Beyond the bedside: a critical perspective on early prediction of chronic pain after mTBI.","authors":"Ibrahim Nagmeldin Hassan","doi":"10.1097/j.pain.0000000000003723","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003723","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 10","pages":"2440-2441"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075803","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":"Marijuana may not be an effective substitute for many chronic pain medications: unobserved variable bias in G-method marginal standardization.","authors":"Jacob James Rich, Chad D Kollas","doi":"10.1097/j.pain.0000000000003731","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003731","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 10","pages":"2439-2440"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075822","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":"Multi-omic integration with human dorsal root ganglia proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway.","authors":"Allison M Barry, Julia R Sondermann, Joseph B Lesnak, Feng Xian, Úrzula Franco-Enzástiga, Jayden A O'Brien, David Gomez-Varela, Morgan K Schackmuth, Stephanie Shiers, Theodore J Price, Manuela Schmidt","doi":"10.1097/j.pain.0000000000003656","DOIUrl":"10.1097/j.pain.0000000000003656","url":null,"abstract":"<p><strong>Abstract: </strong>The peripheral nervous system (PNS) plays a critical role in pathological conditions, including chronic pain disorders, that manifest differently in men and women. To investigate this sexual dimorphism at the molecular level, we integrated quantitative proteomic profiling of human dorsal root ganglia (hDRG) and peripheral nerve tissue into the expanding omics framework of the PNS. Using data-independent acquisition (DIA) mass spectrometry, we characterized a comprehensive proteomic profile, validating tissue-specific differences between the hDRG and peripheral nerve. Through multi-omic analyses and in vitro functional assays, we identified sex-specific molecular differences, with TNFα signalling emerging as a key sexually dimorphic pathway with higher prominence in men. Genetic evidence from genome-wide association studies further supports the functional relevance of TNFα signalling in the periphery, while clinical trial data and meta-analyses indicate a sex-dependent response to TNFα inhibitors. Collectively, these findings underscore a functionally sexual dimorphism in the PNS, with direct implications for sensory and pain-related clinical translation.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"2386-2402"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the association between child maltreatment and chronic pain: a cross-sectional co-twin control study.","authors":"Alynna G Summit,Hsien-Chang Lin,Krista M Wisner,Cen Chen,Erik Pettersson,Katja Boersma,Brian M D'Onofrio,Paul Lichtenstein,Patrick D Quinn","doi":"10.1097/j.pain.0000000000003809","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003809","url":null,"abstract":"Although associations exist between child maltreatment (CM) and multiple chronic painful conditions, it remains unclear to what extent associations might be attributable to unmeasured confounding. We leveraged the co-twin control approach, which rules out genetic and shared environmental confounding by design, with cross-sectional, national Swedish data from the Study of Twin Adults: Genes and Environment (N = 25,418; Mage = 33.2; SDage = 7.7; 55.7% female) to assess associations between the number of self-reported experiences of CM (ie, experiencing emotional or physical abuse/neglect, sexual abuse, or witnessing family violence before age 18 years) and self-reported endorsement of criteria for chronic widespread pain (CWP), lower back pain (LBP), and irritable bowel syndrome (IBS). In negative binomial generalized estimating equation models adjusting for age and sex at birth, a one-unit increase in CM counts was associated with 37%, 18%, and 34% more endorsement of CWP, LBP, and IBS criteria, respectively (CWP-adjusted incidence rate ratio [aIRR] = 1.37 [95% confidence interval: 1.32-1.42]; LBP aIRR = 1.18 [1.16-1.21]; IBS aIRR = 1.34 [1.29-1.39]). In comparisons of differentially exposed co-twins, associations attenuated only slightly for CWP (aIRR, 1.21 [1.12-1.31]), LBP (aIRR, 1.15 [1.09-1.21]), and IBS (aIRR, 1.24 [1.14-1.35]). Analyses restricted to monozygotic twins to rule out virtually all genetic confounding produced similar results (CWP aIRR, 1.20 [1.05-1.38]; LBP aIRR, 1.10 [1.01-1.21]; IBS aIRR, 1.14 [1.00-1.30]). Altogether, the results suggest that associations between CM and CWP, LBP, and IBS are not entirely attributable to genetic or shared environmental confounding.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"28 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194584","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":"Hsp90 inhibition in mouse spinal cord enhances Src kinase signaling in microglia to increase opioid antinociception.","authors":"Jessica L Bowden,Jerry E Carr,Katherin A Gabriel,John M Streicher","doi":"10.1097/j.pain.0000000000003813","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003813","url":null,"abstract":"Opioid drugs are the gold standard for pain management, but have many serious drawbacks, which have highlighted the need for new approaches to improve opioid therapy. Previously, our lab discovered that Heat shock protein 90 (Hsp90), when inhibited in the spinal cord through intrathecal administration of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in mice, led to an increase in morphine antinociception, which could enable an opioid dose-reduction strategy. In this study, we hypothesized that Src kinase was upregulated by 17-AAG treatment to cause this increase. To test this hypothesis, CD-1 mice were treated with 17-AAG and the Src inhibitor Src-I1 or Src CRISPR knockdown, followed by morphine. The enhanced antinociception seen with 17-AAG was completely abolished in the inhibitor groups in tail-flick and paw-incision pain models, suggesting that Hsp90 inhibition activates Src signaling to lead to enhanced opioid pain relief. Analysis by Western blotting showed upregulation of Src by 17-AAG treatment with the opioid agonist DAMGO, and also suggested that Src is upstream of extracellular signal-regulated kinase in this signaling cascade. Immunohistochemistry confirmed the upregulation of Src in the spinal dorsal horn and colocalization of activated Src with microglia. Inhibition of microglia with minocycline/PLX3397 mimicked the 17-AAG effects, while activation with lipopolysaccharide reversed them, suggesting that microglia could regulate these pain states. Finally, we used microglial-specific CRISPR knockdown to confirm that microglial Src is essential to the enhanced opioid antinociception observed with spinal Hsp90 inhibition. These observations elucidate a key molecular mechanism by which Hsp90 regulates microglia and opioid signaling, creating potential targets to improve opioid treatment.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"31 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194587","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":"Syndrome-based classifications: the case for paradigm shifts in the assessment of people with pain.","authors":"Daniel Ciampi de Andrade,Kristian Kjær-Staal Petersen","doi":"10.1097/j.pain.0000000000003812","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003812","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"91 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194645","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 prokineticin system and glia cells as pharmacological targets to control neuroinflammation and to relieve pain in a murine model of Fabry-Anderson disease.","authors":"Giulia Galimberti,Silvia Franchi,Giada Amodeo,Patrizia Romualdi,Sanzio Candeletti,Laura Rullo,Loredana Maria Losapio,Valentina Onnis,Davide Moi,Benedetta Riboldi,Giulia Magni,Stefania Ceruti,Paola Sacerdote","doi":"10.1097/j.pain.0000000000003818","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003818","url":null,"abstract":"Neuropathic pain is a major symptom of Fabry-Anderson disease (FD). It develops in childhood, is life-lasting, and resists current therapies; finding new therapeutic strategies is urgently needed. We demonstrate that neuroinflammation control effectively relieves FD pain. We used 2 pharmacological approaches: the microglial inhibitor minocycline and the block of the activity of the chemokine prokineticin-2 with the specific receptor antagonist PC1 (patented compound 1). Ten- and 25-week-old male GLA-/- mice (the FD murine model) were used. These mice were characterized by mechanical allodynia, thermal hyperalgesia, hyposensitivity to cold stimuli, and abdominal pain. Two weeks of treatment with minocycline or PC1 successfully counteracted sensory alterations. A significant inflammatory state, characterized by high levels of prokineticin-2 and proinflammatory cytokines, was present in the FD gut. The sciatic nerve showed initial severe neuroinflammation that attenuated over time. In dorsal root ganglia, neuroinflammation was severe and persistent with prokineticin-2, proinflammatory cytokines, ionized calcium-binding adapter molecule 1, and glial fibrillary acidic protein overexpression; histone demethylases KDM6A and B were also upregulated. We highlighted neuroinflammation in the spinal cord that increased over time. Treatment with minocycline or PC1 significantly counteracted inflammation and neuroinflammation, reducing prokineticin-2 and proinflammatory cytokines levels and increasing anti-inflammatory factor PPARγ expression. Both treatments prevented the onset of micro- and astrogliosis in the spinal cord. We underline the role of neuroinflammation and microglia in FD pain and suggest that treatments that control the activity of the prokineticin system, glial activation, and the production of proinflammatory cytokines and increase anti-inflammatory mediators have a therapeutic effect on pain in FD.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"1 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194646","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":"Worldwide prevalence of dysmenorrhea: a systematic review and meta-analysis across 70 countries.","authors":"Guilherme Tavares de Arruda,Jordana Barbosa-Silva,Patricia Driusso,Cinthuja Pathmanathan,Susan Armijo-Olivo,Mariana Arias Avila","doi":"10.1097/j.pain.0000000000003768","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003768","url":null,"abstract":"Dysmenorrhea is menstrual pain of uterine origin that can be classified as primary (PD) or secondary (SD). The worldwide prevalence of dysmenorrhea has been estimated in previous systematic reviews; however, these results are often limited by the focus on specific populations, or the inclusion of studies published only in English. Therefore, we estimated the worldwide prevalence of dysmenorrhea of both PD and SD. In this systematic review, we searched 6 databases for studies reporting the prevalence of dysmenorrhea published between 2000 and 2024, without language restriction. The risk of bias of the included studies was assessed using the Joana Briggs Institute tool. Meta-analysis was conducted in Rstudio. The heterogeneity within meta-analyses was evaluated by I2 statistics. Subgroup analyses were performed by PD, SD, age group, and study setting to investigate sources of heterogeneity as well. The certainty of evidence was assessed using GRADE modified for prevalence studies. A total of 336 studies were included in this systematic review. Most of them were conducted in Asia (49.4%). The pooled worldwide prevalence of dysmenorrhea, PD, and SD were 71.3% (95% CI 68.7%-73.8%), 73% (95% CI 68%-78%), and 35% (95% CI 19%-56%), respectively. Dysmenorrhea was more prevalent in Central America (89.6%), Sri Lanka (97.7%), among adults (73.3%), and at universities (78.4%). All subgroup analyses showed high heterogeneity (I2 = 99.5%-100%) with very low certainty of evidence. This high prevalence of dysmenorrhea worldwide highlights the need for healthcare providers and public health organizations to address menstrual pain's global burden.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"31 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194647","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":"Blood-based protein biomarkers of sickle cell disease pain: a systematic review and meta-analysis.","authors":"Mona Mirbeyk,Shubham Misra,Geethika Koneru,Melissa C Funaro,Srikant Rangaraju,Nitya Bakshi","doi":"10.1097/j.pain.0000000000003773","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003773","url":null,"abstract":"Pain is a major complication of sickle cell disease (SCD), and persons with SCD experience acute vaso-occlusive pain episodes (VOEs). Many adults with SCD also develop chronic pain (CP). We conducted a systematic review and meta-analysis (PROSPERO CRD42024535776) to evaluate blood-based protein biomarkers of SCD pain in 3 clinical contexts: VOE (objective 1), frequency of VOE (objective 2), and CP (objective 3). We searched 5 electronic databases through November 26, 2024. The search yielded 151 eligible observational studies on 159 biomarkers, including 10,208 persons with SCD. Most biomarkers were evaluated during acute pain and were biomarkers of pain biology, inflammation, immune activation, coagulation, and hemolysis or tissue damage. A meta-analysis was conducted for biomarkers reported in 2 or more studies: 80 biomarkers for objective 1, 7 for objective 2, and 4 for objective 3, respectively. We found 28 biomarkers with higher and 2 with lower levels in VOE compared with steady state. No biomarker was associated with frequency of VOE or with chronic SCD pain. This work summarizes the existing literature to provide quantitative estimates of biomarker effect sizes and offers insights from existing literature on pathways implicated in SCD pain. This work highlights the limitations of current approaches and gaps in the scientific literature and supports the premise of using unbiased proteomic platform-based approaches for biomarker discovery in future studies. We highlight the goals and challenges of identifying biomarkers in SCD pain and propose conceptual and methodological considerations to advance the field of protein biomarker research in SCD.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"78 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103317","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":"Neural, psychological, and daily life evidence for a transdiagnostic process of affective dysregulation in depression and chronic widespread pain.","authors":"Malika Pia Renz,Hannah Schmidt,Armin Drusko,Oksana Berhe,Francesca Zidda,Carina Sebald,Jamila Andoh,Sebastian Wieland,Jonas Tesarz,Rolf-Detlef Treede,Andreas Meyer-Lindenberg,Heike Tost","doi":"10.1097/j.pain.0000000000003800","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003800","url":null,"abstract":"Chronic pain and depression are leading causes of disability, frequently co-occurring and exacerbating each other. This cross-sectional study investigated putative transdiagnostic processes of affective dysregulation in fibromyalgia (FMS) and major depressive disorder (MDD) using psychometric questionnaires (Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Cognitive Emotion Regulation Questionnaire, Perceived Stress Scale, Widespread Pain Index, Somatic Symptom Disorder B Criteria Scale 12), ecological momentary assessments, and real-time functional magnetic resonance imaging amygdala neurofeedback during an emotion regulation task. We compared clinical symptoms, stress sensitivity, and emotion regulation in patients with FMS (N = 46) and MDD (N = 48) with healthy controls (N = 34). Patients with fibromyalgia syndrome and major depressive disorder reported similar psychopathological and affective dysregulation profiles, and they exhibited more psychopathology and emotion regulation deficits than healthy controls (HC). Differences between MDD and FMS were limited to pain-specific pathology in FMS (pain spread and frequency P < 0.001, intensity P < 0.05) and more rumination (P < 0.05) and self-blame (P < 0.01) in MDD. Momentary stress predicted higher subsequent pain and worse affective states across groups, with FMS and MDD exhibiting stronger stress responses (all P's < 0.05). Directly after neurofeedback training, FMS and MDD were less able to downregulate left amygdala activity than HC (P = 0.039) compared to baseline performance, and this brain marker predicted daily life psychopathology (negative affect, anxiety, and rumination, all P's < 0.05). Patients with fibromyalgia syndrome additionally exhibited unique deficits in right amygdala regulation (P = 0.004). Our findings highlight transdiagnostic affective dysregulation patterns in FMS and MDD, specific differences in emotion regulation strategies, and a potential neuronal marker of a shift towards right amygdala sensitization during affective processing in FMS.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"20 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103454","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}