PAIN®最新文献

{"title":"Autoantibodies in patients with fibromyalgia syndrome.","authors":"Sabine Seefried, Anastasia Barcic, Maria Fernanda Grijalva Yepez, Lena Reinhardt, Luise Appeltshauser, Kathrin Doppler, Nurcan Üçeyler, Claudia Sommer","doi":"10.1097/j.pain.0000000000003535","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003535","url":null,"abstract":"<p><strong>Abstract: </strong>The objective of this study was to assess the frequency of IgG autoantibodies in patients with fibromyalgia syndrome (FMS), to characterize their binding to dorsal root ganglion (DRG) neurons and glial cells, and to assess whether specific DRG binding patterns correlate with clinical symptoms. Sera of a cohort of 184 patients with FMS and 55 control sera were used to test binding of patient IgG on rat DRG sections. ELISA, Western blot, and preadsorption tests were used to search for potential target antigens. We found binding to DRGs in 68 of 184 FMS sera and in none of the control sera. We could identify 9 binding clusters including binding to neurons and to cells labelled with the satellite glial cell marker fatty acid binding protein 7 (FABP7). Current pain intensity correlated positively with IgG binding to FABP7 immunoreactive structures, and burning pain was associated with binding to transient receptor potential vanilloid 1 immunoreactive neurons. Specific antibody detection revealed 13 of 68 sera positive for anti-citrullinated peptide antibodies, 9 of 68 positive for SOX1 antibodies, 7 of 68 positive for antibodies against the serotonin receptor 5HT1AR, and 3 of 68 positive for fibroblast growth factor 3 antibodies. Our findings support the notion of an immune activation in a subgroup of patients with FMS.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190195","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":"Social determinants of health in pediatric chronic postsurgical pain research.","authors":"Wendy Gaultney, Nathalia Jimenez, Abraham Correa-Medina, Claudia M Campbell, Jennifer Anne Rabbitts","doi":"10.1097/j.pain.0000000000003510","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003510","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188714","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":"Somatosensory and clinical profiles of patients with spine-related and clinical framework-based neck-arm pain.","authors":"Camilla Kapitza, Nikolaus Ballenberger, Kerstin Luedtke, Annina B Schmid, Brigitte Tampin","doi":"10.1097/j.pain.0000000000003516","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003516","url":null,"abstract":"<p><strong>Abstract: </strong>Spine-related neck-arm pain is heterogeneous and may present on a spectrum between nociceptive and neuropathic pain. A recently developed mechanism-based clinical framework for spine-related pain distinguishes between spinally referred pain without neurological deficits (somatic referred pain, heightened nerve mechanosensitivity, radicular pain), with neurological deficits (radiculopathy), and mixed-pain presentations. This study investigated differences in somatosensory and clinical profiles of patients with unilateral spine-related neck-arm pain grouped according to the clinical framework. Patients (n = 113) underwent a clinical examination, after which they were classified into a subgroup(s). They completed questionnaires to assess function (Neck Disability Index), psychosocial factors (Tampa Scale of Kinesiophobia, pain catastrophizing scale, Depression, anxiety, and stress scale), neuropathic pain (Douleur neuropathique 4), and central sensitization features (Central Sensitization Inventory). Standardized quantitative sensory testing (QST) was performed over the maximal pain area and contralateral side. The radiculopathy group showed a significant loss of function on the symptomatic vs asymptomatic side in cold (P = 0.024) and warm detection (P = 0.004), thermal sensory limen (P = 0.001), mechanical detection (P = 0.001), increased windup ratio (P = 0.014), and cold hyperalgesia (P = 0.049). No other subgroup showed significant side differences in QST parameters. Symptom descriptors, such as burning (P < 0.031), tingling (P < 0.018), pins and needles (P < 0.031), numbness (P < 0.016), spontaneous pain (P < 0.001), and electric pain/shock (P < 0.026) were more common in the radicular/radiculopathy groups compared with the somatic/mechanosensitivity groups. There were no differences in psychosocial parameters between the groups. The phenotypic profiles support the construct of the clinical examination and patient classification and its application in clinical practice according to a clinical framework for spine-related pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188798","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":"Conditioned pain modulation: controlling for the order of baseline and conditioning.","authors":"Stefan Lautenbacher, Claudia Horn-Hofmann, Miriam Kunz","doi":"10.1097/j.pain.0000000000003494","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003494","url":null,"abstract":"<p><strong>Abstract: </strong>Conditioned pain modulation (CPM) is assumed to capture endogenous pain modulation. In standard CPM designs, the evaluation of a painful test stimulus (TS) (baseline) is followed by a second evaluation of the TS during/after application of a painful conditioning stimulus (CS) (treatment). However, these standard CPM within designs (baseline always preceding treatment) do not control for order effects, which might help to distinguish specific CPM inhibition from general habituation. To tackle this issue, we conducted 2 separate studies where we controlled for order effects to investigate whether CPM effects depend on the order of baseline and treatment. In both studies, a sample of 60 participants underwent 2 CPM test blocks: one standard order block (baseline before treatment) and one reversed order block (treatment before baseline), separated by a 20-minute break (randomized order across participants). Pain thresholds and pain ratings of phasic heat stimuli served as measures of TS. Cold water (study 1) and cuff pressure algometry (study 2) served as CS. We found significant CPM order effects in both studies and for both measures of TS (pain threshold and ratings). Only the standard CPM order (baseline before treatment) yielded robust pain inhibition effects, whereas the reversed order (treatment before baseline) led to no modulation or seeming pain facilitation. Because control for order effects is otherwise mandatory in within designs, it is surprising that it has been neglected in standard CPM protocols. Finding pain inhibition only in the standard CPM order suggests that CPM inhibition is at least partially confounded with habituation.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190196","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":"PI3K-mediated Kif1a DNA methylation contributes to neuropathic pain: an in vivo study.","authors":"Wei Jiang, Peng Yu, Yu Yang, Meng-Tan Cai, Lin Gan, Kang Qu, Ying-Ying Cheng, Ming Dong","doi":"10.1097/j.pain.0000000000003536","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003536","url":null,"abstract":"<p><strong>Abstract: </strong>Neuropathic pain (NP) is a chronic condition caused by nerve injuries, such as nerve compression. Understanding its underlying neurobiological mechanisms is critical for developing effective treatments. Previous studies have shown that Kinesin family member 1A (Kif1a) heterozygous deficient mice display sensory deficits in response to nociceptive stimuli. PI3K has been found to mitigate these sensory deficits by enhancing Kif1a transcription, highlighting KIF1A's key role in sensory pain. However, the exact mechanism through which PI3K regulates KIF1A expression in relation to pain remains unclear. In this study, we observed a significant increase in PI3K/AKT/CREB (cyclic AMP response element-binding protein) protein levels in the dorsal root ganglia and spinal cord after chronic constriction injury in both male and female C57BL/6 mice. Notably, elevated levels of TET1, as well as Kif1a mRNA and protein, were detected in both male and female mice. Activated (phosphorylated-CREB) p-CREB recruited the DNA demethylase TET1, which interacted with the Kif1a promoter, reducing methylation and increasing Kif1a mRNA and protein expression. PI3K inhibition using wortmannin reversed the demethylation of Kif1a and decreased its expression in male mice. Furthermore, TET1 knockdown or overexpression significantly affected pain-related behaviors, as well as Kif1a methylation and transcription. Female mice given intrathecal injections of PI3K inhibitors exhibited similar molecular and behavioral outcomes as male mice. These findings offer new insights into NP mechanisms, suggesting that targeting the PI3K/KIF1A axis could be a promising therapeutic approach for NP treatment.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190198","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":"Potentiation of visualized exosomal miR-1306-3p from primary sensory neurons contributes to chronic visceral pain via spinal P2X3 receptors.","authors":"Qian Sun, Rui-Xia Weng, Yong-Chang Li, Shu-Man Jia, Chun-Tao Ma, Hong-Hong Zhang, Yong Tang, Rui Li, Guang-Yin Xu","doi":"10.1097/j.pain.0000000000003537","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003537","url":null,"abstract":"<p><strong>Abstract: </strong>Exosomes served as \"communicators\" to exchange information among different cells in the nervous system. Our previous study demonstrated that the enhanced spinal synaptic transmission contributed to chronic visceral pain in irritable bowel syndrome. However, the underlying mechanism of primary sensory neuron (PSN)-derived exosomes on spinal transmission remains unclear. In this study, an exosome visualization method was established to specifically track exosomes derived from PSNs in CD63-GFPf/+ (green fluorescent protein) mice. Neonatal maternal deprivation (NMD) was adopted to induce chronic visceral pain in CD63-GFPf/+ male mice. The exosome visualization technology demonstrated that NMD increased visible PSN-derived exosomes in the spinal dorsal horn, enhanced spinal synaptic transmission, and led to visceral pain in CD63-GFPf/+ male mice. The PSN-derived exosomal miR-1306-3p sorted from spinal dorsal horn activated P2X3R, enhanced spinal synaptic transmission, and led to visceral pain in NMD mice. Moreover, upregulation of Rab27a in dorsal root ganglia mediated the increased release of PSN-derived exosomes, and intrathecal injection of siR-Rab27a reduced visible PSN-derived exosomes in spinal cord, suppressed spinal synaptic transmission, and alleviated visceral pain in NMD mice. This and future studies would reveal the detailed mechanisms of PSN-derived exosomes and provide a potential target for clinical treatment of chronic visceral pain in patients with irritable bowel syndrome.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190200","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":"Standardizing research methods for opioid dose comparison: the NIH HEAL morphine milligram equivalent calculator.","authors":"Meredith C B Adams, Katherine A Sward, Matthew L Perkins, Robert W Hurley","doi":"10.1097/j.pain.0000000000003529","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003529","url":null,"abstract":"<p><strong>Abstract: </strong>We developed the National Institutes of Health helping to end addiction long-term initiative morphine milligram equivalent (MME) calculator to standardize MME calculations across pain research studies, addressing a critical barrier to effective research synthesis and meta-analysis. The tool provides evidence-based mapping factors for 29 opioids through a research electronic data capture-based calculator and companion Web site (research-mme.wakehealth.edu). Development involved systematic evidence evaluation of literature from 1949 to March 2024, following PRISMA guidelines. From an initial screening of over 170,050 articles, we identified 24 studies providing evidence for conversion factors. The calculator incorporates 4 standardized time-window calculation methods aligned with current research approaches and includes traditional full agonists, partial agonists, and mixed-mechanism agents. Using modified GRADE methodology, we evaluated evidence quality for each conversion factor, documenting levels from high-quality randomized controlled trials to pharmacokinetic extrapolation. Our tool replicates most existing Centers for Disease Control and Prevention (CDC) conversion factors while expanding coverage to 7 additional opioids and 6 formulations not included in the 2022 CDC conversion table. The calculator features options to analyze results with or without buprenorphine, accommodating its emerging role in pain research. This standardized framework enables researchers to map opioid doses using consistent, evidence-based ratios and harmonize data collection across research networks. While the tool represents a significant advance in standardizing MME calculations for research, limitations in the underlying evidence base highlight the need for continued validation through clinical research.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189437","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":"An examination of acrylamide and cadmium as possible mediators of the association between cigarette smoking and chronic musculoskeletal pain.","authors":"Codjo Djignefa Djade, Caroline Diorio, Danielle Laurin, Denis Talbot, Pierre-Hugues Carmichael, Clermont E Dionne","doi":"10.1097/j.pain.0000000000003517","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003517","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic musculoskeletal pain (CMP) causes significant health loss worldwide and is one of the major public health issues of our time. Cigarette smoking is an independent risk factor of CMP. The present study examined the potential mediating role of 2 subproducts of cigarette smoke, acrylamide and cadmium, individually and combined, on the association between cigarette smoking and CMP, using the Inverse Odds Ratio Weighting (IORW) method. Analyses were conducted on data from 3670 adults who participated to National Health and Nutrition Examination Surveys 2003 to 2004. When smoking was measured with serum cotinine levels, there was an association of moderate and heavy smoking {adjusted Odds Ratio [aOR]>30 ng/mL = 1.99 (95% confidence interval [CI]: 1.44-2.74)} with CMP, but no association between light smoking and CMP (aOR1-30 ng/mL = 1.17 [95% CI: 0.75-1.80]) as compared to nonsmoking. Small indirect effects were identified through acrylamide (aOR = 1.24 [95% CI: 0.96-1.61]) and cadmium (aOR = 1.56 [95% CI: 0.92-2.63]) only among moderate and heavy smokers. When both biomarkers were considered together, their indirect effect was larger (aOR = 2.07 [95% CI: 1.32-3.23]). These results suggest that the association between cigarette smoking and CMP is mediated by acrylamide and cadmium and that these substances, also present in food and the environment, may serve as biomarkers of CMP.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190194","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":"Emergent epileptiform activity in spinal sensory circuits drives ectopic bursting in afferent axons and sensory dysfunction after cord injury.","authors":"Matthew Bryson, Heidi Kloefkorn, Shaquia Idlett-Ali, Dario I Carrasco, Donald James Noble, Karmarcha Martin, Michael A Sawchuk, Nicholas Au Yong, Sandra M Garraway, Shawn Hochman","doi":"10.1097/j.pain.0000000000003364","DOIUrl":"10.1097/j.pain.0000000000003364","url":null,"abstract":"<p><strong>Abstract: </strong>Spinal cord injury leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform, we explored whether such activity emerges in a thoracic spinal cord injury (SCI) contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which were correlated across multiple adjacent dorsal roots. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABA A receptor activation, presumably by conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of an epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (fampridine). We conclude that spinal cord injury promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes hyperexcitability and bursting by ectopic spiking in afferent axons that propagate bidirectionally by reentrant central and peripheral projections as well as sensory circuit hypoexcitability during the burst refractory period. More broadly, the work links circuit hyperexcitability to epileptiform circuit emergence, further strengthening it as a conceptual basis to understand features of sensory dysfunction and neuropathic pain.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"e27-e35"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897973","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":"High-frequency electrical stimulation increases cortical excitability and mechanical sensitivity in a chronic large animal model.","authors":"Suzan Meijs, Felipe Rettore Andreis, Taha Al Muhammadee Janjua, Thomas Graven-Nielsen, Winnie Jensen","doi":"10.1097/j.pain.0000000000003354","DOIUrl":"10.1097/j.pain.0000000000003354","url":null,"abstract":"<p><strong>Abstract: </strong>Translational models of the sensitized pain system are needed to progress the understanding of involved mechanisms. In this study, long-term potentiation was used to develop a mechanism-based large-animal pain model. Event-related potentials to electrical stimulation of the ulnar nerve were recorded by intracranial recordings in pigs, 3 weeks before, immediately before and after, and 3 weeks after peripheral high-frequency stimulation (HFS) applied to the ulnar nerve in the right forelimb (7 pigs) or in control animals (5 pigs). Event-related potential recordings and peripheral HFS were done during anesthesia. Two weeks before and after the HFS, behavioral responses reflecting mechanical and thermal sensitivity were collected using brush, noxious limb-mounted pressure algometer, and noxious laser stimuli. The HFS intervention limb was progressively sensitized to noxious mechanical stimulation in week 1 and 2 compared with baseline ( P = 0.045) and the control group ( P < 0.034) but not significantly to laser or brush stimulation. The first negative (N1) peak of the event-related potential was increased 30 minutes after HFS compared with before ( P < 0.05). The N1 peak was also larger compared with control pigs 20 to 40 minutes after HFS ( P < 0.031) but not significantly increased 3 weeks after. The relative increase in N1 30 minutes after HFS and the degree of mechanical hyperalgesia 2 weeks post-HFS was correlated ( P < 0.033). These results show for the first time that the pig HFS model resembles the human HFS model closely where the profile of sensitization is comparable. Interestingly, the degree of sensitization was associated with the cortical signs of hyperexcitability at HFS induction.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"e18-e26"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917326","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}