IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2024-12-03 DOI: 10.1097/j.pain.0000000000003486

Maryam Kazemi Naeini, Marina Cecelja, Maxim B Freidin, Isabelle Granville Smith, Pirro Hysi, Christopher Sivert Nielsen, Frances M K Williams

{"title":"Chronic widespread musculoskeletal pain shares a highly heritable latent pathway with atherosclerosis and arterial stiffness.","authors":"Maryam Kazemi Naeini, Marina Cecelja, Maxim B Freidin, Isabelle Granville Smith, Pirro Hysi, Christopher Sivert Nielsen, Frances M K Williams","doi":"10.1097/j.pain.0000000000003486","DOIUrl":"10.1097/j.pain.0000000000003486","url":null,"abstract":"Abstract: Chronic widespread pain (CWP) is prevalent and associated with reduced life expectancy. Cardiovascular disease is one possible mechanism for this. The purpose of this study was to examine the association of CWP with arterial stiffness and carotid plaque measured using ultrasound to determine if shared environmental or genetic factors might account for any observed association. Around 3000 participants from the TwinsUK with CWP information and measures of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and plaque were considered. The relationship between CWP and cfPWV, cIMT, and plaque was determined. UK Biobank data were used to replicate the association. Cholesky decomposition and multivariate pathway twin models were examined. Using a 2-sample Mendelian randomisation approach, the causal association between CWP and coronary artery disease was assessed. TwinsUK participants demonstrated a significant association between CWP and increased cfPWV consistent with arterial stiffening (OR = 1.35, P -value = 0.012), as well as the presence of carotid plaque (OR = 1.45, P -value = 0.8e-5). The twin modelling showed a common latent component and pathway underlying CWP, cfPWV, and carotid plaque, with genetic factors accounting for 68% and 90% of the latent factor variation, respectively. The 2-sample MR revealed a potential causal association between CWP and coronary artery disease. This study found that those with CWP have increased the risk of arterial stiffness and atherosclerosis and suggests that CWP leads to an increased risk of cardiovascular disease through genetic factors.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1425-1435"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771232","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}

引用次数: 0

Reply to Bhatt and Forget. 回复那件事然后忘记。

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2025-02-25 DOI: 10.1097/j.pain.0000000000003576

Chihua Li, Peiyi Lu

引用次数: 0

Advancements in noninvasive brain stimulation: exploring repetitive transcranial magnetic stimulation of the posterior superior insula for pain relief. 非侵入性脑部刺激的进展：探索重复经颅磁刺激后上岛叶缓解疼痛的方法。

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2024-12-12 DOI: 10.1097/j.pain.0000000000003489

Giulia Liberati

引用次数: 0

Pain in functional gastrointestinal disorders: nociplastic pain or something else? 功能性胃肠疾病的疼痛：伤害性疼痛还是别的什么？

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2025-02-05 DOI: 10.1097/j.pain.0000000000003547

Antonio Alcántara Montero

引用次数: 0

Estrous cycle regulates cephalic mechanical sensitivity and sensitization of the trigemino-cervical complex in a female rat model of chronic migraine. 在慢性偏头痛雌性大鼠模型中，动情周期调节头颅机械敏感性和三叉神经-颈椎复合体的敏感性。

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2024-10-30 DOI: 10.1097/j.pain.0000000000003459

Maxime Barnet, Amelie Descheemaeker, Lea Favier, Xavier Moisset, Julien Schopp, Radhouane Dallel, Alain Artola, Lenaic Monconduit, Myriam Antri

{"title":"Estrous cycle regulates cephalic mechanical sensitivity and sensitization of the trigemino-cervical complex in a female rat model of chronic migraine.","authors":"Maxime Barnet, Amelie Descheemaeker, Lea Favier, Xavier Moisset, Julien Schopp, Radhouane Dallel, Alain Artola, Lenaic Monconduit, Myriam Antri","doi":"10.1097/j.pain.0000000000003459","DOIUrl":"10.1097/j.pain.0000000000003459","url":null,"abstract":"Abstract: The higher incidence of migraines in women compared with men has led to the inclusion of female animals in pain research models. However, the critical role of the hormonal cycle is frequently overlooked, despite its clear correlation with migraine occurrences. In this study, we show in a rat model of migraine induced by repeated dural infusions of an inflammatory soup (IS) that a second IS (IS2) injection performed in proestrus/estrus (PE, high estrogen) female rats evokes higher cephalic mechanical hypersensitivities than when performed in metestrus/diestrus (MD, low estrogen) or ovariectomized (OV) rats. This hypersensitivity induced by IS2 correlates with increased c-Fos expression in outer lamina II (IIo) neurons located in the periorbital projection area of the trigemino-cervical complex (TCC), in PE only. Four IS (IS4) repetition induced an enlargement of c-Fos expression in adjacent territories areas in PE, but not MD or OV animals. Unexpectedly, c-Fos expression in locus coeruleus neurons does not potentiate after IS2 or IS4 injections. To examine the impacts of the hormonal cycle on the physiology of lamina II o TCC neurons, we performed whole-cell patch-clamp recordings. Second inflammatory soup depolarizes neurons in PE and MD but not in OV rats and enhances excitatory synaptic inputs in PE animals to a greater extent compared with MD and OV rats. These findings show that central TCC sensitization triggered by meningeal nociceptor activation and the resulting cephalic hypersensitivity are modulated by the estrous cycle. This highlights the crucial need to account for not just sex, but also the female estrous cycle in pain research.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"e83-e96"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546663","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}

引用次数: 0

A 5-day course of repetitive transcranial magnetic stimulation before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency. 疼痛发作前5天的反复经颅磁刺激可改善未来的疼痛并增加感觉运动α峰频率。

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2024-12-03 DOI: 10.1097/j.pain.0000000000003484

Nahian S Chowdhury, Khandoker J Taseen, Alan Ki Chiang, Wei-Ju Chang, Samantha K Millard, David A Seminowicz, Siobhan M Schabrun

{"title":"A 5-day course of repetitive transcranial magnetic stimulation before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.","authors":"Nahian S Chowdhury, Khandoker J Taseen, Alan Ki Chiang, Wei-Ju Chang, Samantha K Millard, David A Seminowicz, Siobhan M Schabrun","doi":"10.1097/j.pain.0000000000003484","DOIUrl":"10.1097/j.pain.0000000000003484","url":null,"abstract":"Abstract: Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine whether (1) 5 consecutive days of rTMS delivered prior to experimentally induced prolonged jaw pain has a prophylactic effect on future pain intensity and (2) whether these effects were accompanied by increases in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from day 0 to 4, 40 healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. Peak alpha frequency and CME were assessed on day 0 (before rTMS) and day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor in the right masseter muscle after the final rTMS session. From days 5 to 25, participants completed twice-daily electronic diaries including pain on chewing and yawning (primary outcomes), as well as pain during other activities (eg, talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Furthermore, active rTMS led to an increase in PAF. This is the first study to show that rTMS delivered prior to prolonged pain onset can protect against future pain. Our findings suggest that rTMS may hold promise as a prophylactic intervention for pain.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1382-1394"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771229","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}

引用次数: 0

Individual differences in conditioned pain modulation are associated with functional connectivity within the descending antinociceptive pathway. 条件性疼痛调节的个体差异与下行抗感觉通路内的功能连接有关。

IF 5.9 1区医学

PAIN® Pub Date : 2025-06-01 Epub Date: 2024-11-19 DOI: 10.1097/j.pain.0000000000003478

Janet Z Li, Emily P Mills, Natalie R Osborne, Joshua C Cheng, Vaidhehi V Sanmugananthan, Rima El-Sayed, Ariana Besik, Junseok A Kim, Rachael L Bosma, Anton Rogachov, Karen D Davis

{"title":"Individual differences in conditioned pain modulation are associated with functional connectivity within the descending antinociceptive pathway.","authors":"Janet Z Li, Emily P Mills, Natalie R Osborne, Joshua C Cheng, Vaidhehi V Sanmugananthan, Rima El-Sayed, Ariana Besik, Junseok A Kim, Rachael L Bosma, Anton Rogachov, Karen D Davis","doi":"10.1097/j.pain.0000000000003478","DOIUrl":"10.1097/j.pain.0000000000003478","url":null,"abstract":"Abstract: The perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM). A total of 151 healthy participants (72 men, 79 women) underwent CPM testing and rs-fMRI. Three types of CPM were identified based on the effect of the CS on TS pain: (1) Antinociception: CS reduced TS pain in 45% of participants, (2) No-CPM: CS did not change TS pain in 15% of participants, and (3) Pronociception: CS increased TS pain in 40% of participants. Only the Antinociceptive subgroup exhibited FC between the left sgACC and PAG, right sgACC and PAG, and RVM and PAG. Furthermore, only the Antinociceptive subgroup exhibited a correlation of both left and right sgACC-RVM FC (medium effect sizes) with CPM effect magnitude. Women, compared with men were more likely to be categorized as pronociceptive. These data support the proposition that FC of the DAP reflects or contributes to inhibitory CPM.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"1436-1449"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807851","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}

引用次数: 0

Endophilin A1 and synaptojanin 1-dependent endocytosis of synaptic vesicles in nociceptive spinal circuits maintains postoperative and cancer pain. 痛觉性脊髓回路中突触囊泡的嗜内蛋白A1和突触蛋白1依赖性内吞维持术后和癌性疼痛。

IF 5.9 1区医学

PAIN® Pub Date : 2025-05-27 DOI: 10.1097/j.pain.0000000000003657

Maria Fernanda Pessano Fialho, Gokul Sriman Thanigai Arasu, Shen Chen, Wendy L Imlach, Nigel W Bunnett, Raquel Tonello

{"title":"Endophilin A1 and synaptojanin 1-dependent endocytosis of synaptic vesicles in nociceptive spinal circuits maintains postoperative and cancer pain.","authors":"Maria Fernanda Pessano Fialho, Gokul Sriman Thanigai Arasu, Shen Chen, Wendy L Imlach, Nigel W Bunnett, Raquel Tonello","doi":"10.1097/j.pain.0000000000003657","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003657","url":null,"abstract":"Abstract: The continued release of neurotransmitters from central projections of nociceptors during chronic pain requires synaptic vesicle (SV) recycling. Mediators of SV endocytosis and recycling are thus pivotal for sustained pain transmission in nociceptive spinal circuits. We hypothesized that disruption of SV endocytosis in dorsal root ganglia (DRG) nociceptors would impede synaptic transmission and thereby provide sustained relief from multimodalities of pain. Synaptojanin 1 (Synj1) and endophilin A1 (EndoA1), which mediate the neck formation of the endocytic pit and subsequent endocytosis, were detected in primary sensory neurons of mouse DRG by immunofluorescence and RNAScope in situ hybridization. Intrathecal injection of Synj1 and EndoA1 siRNA or shRNA successfully knocked down Synj1 and Sh3gl2 (EndoA1) mRNA in DRG neurons and suppressed acute nociception induced by agonists of pronociceptive receptors and ion channels in male mice, without affecting normal motor functions. Synj1 and EndoA1 knockdown inhibited synaptic transmission between primary sensory neurons and neurons in lamina I/II of the spinal cord dorsal horn by suppressing SV release from presynaptic primary afferent neurons. Synj1 and EndoA1 silencing reversed mechanical allodynia and thermal hyperalgesia in preclinical models of postoperative and cancer pain. Knockdown of dynamin 1 (Dnm1) and adaptor-associated protein kinase 1 (AAK1), previously characterized mediators of SV endocytosis in nociceptive spinal circuits, also alleviated pain-like behavior in these models. Thus, Synj1, EndoA1, Dnm1, and AAK1 mediate SV recycling and are thus required for sustained synaptic transmission in nociceptive spinal circuits. Disruption of SV recycling effectively reduces nociceptive transmission, providing a novel strategy for pain relief.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249139","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}

引用次数: 0

Disrupted spatial but not temporal aspects of nociceptive processing determine painful polyneuropathies. 破坏的空间而不是时间方面的伤害性加工决定了疼痛性多发性神经病。

IF 7.4 1区医学

PAIN® Pub Date : 2025-05-23 DOI: 10.1097/j.pain.0000000000003666

Wacław M Adamczyk,Nick Berendt,Peter Trillenberg,Janina Hanssen,Jakob Poehlmann,Camilla Kapitza,Luisa Luebke,Kerstin Luedtke,Norbert Brüggemann,Tibor M Szikszay

{"title":"Disrupted spatial but not temporal aspects of nociceptive processing determine painful polyneuropathies.","authors":"Wacław M Adamczyk,Nick Berendt,Peter Trillenberg,Janina Hanssen,Jakob Poehlmann,Camilla Kapitza,Luisa Luebke,Kerstin Luedtke,Norbert Brüggemann,Tibor M Szikszay","doi":"10.1097/j.pain.0000000000003666","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003666","url":null,"abstract":"Polyneuropathy remains a diagnostic and clinical challenge, with limited understanding of the mechanisms underlying painful and nonpainful phenotypes. While previous studies have examined various characteristics of these patients, the temporal and spatial dynamics of endogenous pain modulation remains not fully elucidated. In this study, offset analgesia (OA) and spatial summation of pain (SSp) were used as measures of pain modulation in individuals with distal symmetric polyneuropathy, stratified by the presence (n = 30) or absence of pain (n = 30), and compared with healthy controls (n = 30). All participants underwent quantitative sensory testing and assessments of OA and SSp using a thermal stimulator applied to the dorsum of the foot. Patients with painful polyneuropathy exhibited enhanced SSp compared with the pain-free polyneuropathy group and healthy controls (P < 0.05), and impaired OA compared with healthy controls (P < 0.05). The pain-free neuropathy group showed less efficient OA and a slightly enhanced SSp, but this finding did not reach significance. The data suggest that changes in spatial summation were primarily driven by heightened pain responses to nociceptive input from smaller areas, rather than larger ones. Notably, spatial summation and the effects of OA were found to be correlated, irrespective of pain diagnosis. These findings underscore specific impairments in endogenous pain modulation in individuals with painful neuropathy, thus advancing our understanding of its pathophysiological mechanisms. They further highlight the differential roles of spatial and temporal dynamics in pain modulation across various neuropathic populations, offering promising avenues for improved diagnostics and prognostics related to polyneuropathy-associated pain.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"47 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130685","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}

引用次数: 0

Progression trajectories of chronic overlapping pain conditions unveiled across two large clinical data warehouses. 两个大型临床数据仓库揭示了慢性重叠疼痛状况的进展轨迹。

IF 7.4 1区医学

PAIN® Pub Date : 2025-05-23 DOI: 10.1097/j.pain.0000000000003650

Haiquan Li,Jungwei W Fan,Edwin Baldwin,Wenting Luo,Jin Zhou,W Michael Hooten

{"title":"Progression trajectories of chronic overlapping pain conditions unveiled across two large clinical data warehouses.","authors":"Haiquan Li,Jungwei W Fan,Edwin Baldwin,Wenting Luo,Jin Zhou,W Michael Hooten","doi":"10.1097/j.pain.0000000000003650","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003650","url":null,"abstract":"Chronic overlapping pain conditions (COPCs) affect a wide population and incur a substantial disease burden including comorbid mental disorders. Although these comorbidities have been extensively documented, the longitudinal trajectories of their onset, particularly for those with three or more conditions, have been rarely studied. We conducted retrospective cohort studies to identify statistically significant COPCs and mental health trajectories in the All of Us Research Program (AoU v8, 338,170 persons) and the Mayo Data Warehouse (3,957,444 individuals). For each trajectory, cases were matched with controls by demographic factors. Logistic regression was then applied to assess the increased likelihood of the final condition given the prior conditions in that sequence. The significant trajectories were visualized as a \"pain forest.\" More than 88% of trajectories identified from AoU (Male: 78, Female: 361) were reproducible in the Mayo Data Warehouse data (Male: 361, Female: 1286), with female trajectories encompassing more than 96% of the male trajectories. The findings indicate that chronic low back pain generally occurs earlier than other conditions, while fibromyalgia tends to follow other COPCs. Endometriosis seems to be associated with an increased prevalence of COPCs in women. In addition, longer trajectories are associated with a greater risk of developing additional COPC or mental condition. The results offer new insights into the progression of COPCs and associated mental conditions, which may inform healthcare providers and patients in managing and preventing exacerbation of these conditions.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"142 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130686","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}

引用次数: 0

PAIN®最新文献