PAIN®最新文献 - Book学术

Androgen receptors expressed in the primary sensory neurons regulate mechanical pain sensitivity. 在初级感觉神经元中表达的雄激素受体调节机械疼痛敏感性。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-16 DOI: 10.1097/j.pain.0000000000003736

Fumihiro Saika,Daisuke Uta,Yohji Fukazawa,Yuko Hino,Yu Hatano,Shiroh Kishioka,Hiroyuki Nawa,Shinjiro Hino,Kentaro Suzuki,Norikazu Kiguchi

{"title":"Androgen receptors expressed in the primary sensory neurons regulate mechanical pain sensitivity.","authors":"Fumihiro Saika,Daisuke Uta,Yohji Fukazawa,Yuko Hino,Yu Hatano,Shiroh Kishioka,Hiroyuki Nawa,Shinjiro Hino,Kentaro Suzuki,Norikazu Kiguchi","doi":"10.1097/j.pain.0000000000003736","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003736","url":null,"abstract":"The expression of hormonal receptors in pain-processing regions complicates understanding the hormonal effects on pain mechanisms. This study investigates androgen receptor (AR) involvement in pain sensitivity and sex differences in pain perception. Mechanical pain thresholds were higher in normal male mice compared to gonadectomized (GDX) male and normal female mice, correlating with serum testosterone levels. In the dorsal root ganglia (DRG), AR was expressed in normal males but undetectable in GDX males and normal females. Androgen receptor overlapped with NeuN, a neuronal nuclei marker, indicating androgen signaling activation in sensory neurons. In male sensory neuron-selective AR conditional knockout (AR-cKO) mice, mechanical pain thresholds were significantly lower than in wild-type males, with the greatest AR depletion in calcitonin gene-related peptide (CGRP)+ neurons. Electrophysiological analyses revealed increased excitability of spinal dorsal horn neurons in both GDX males and AR-cKO males. In female mice, administration of testosterone propionate or dihydrotestosterone significantly raised mechanical pain thresholds, accompanied by increased AR expression in the DRG. This effect was abolished in AR-cKO females, where AR depletion was most prominent in CGRP+ neurons, consistent with male findings. These results indicate that primary sensory neurons, particularly CGRP+ neurons, are critical targets of androgen in regulating mechanical pain sensitivity. Therefore, manipulating androgen signaling in sensory neurons may offer a promising approach to managing mechanical pain.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"84 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639739","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

Neurophysiological encoding of aversive prediction errors. 厌恶预测误差的神经生理编码。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-16 DOI: 10.1097/j.pain.0000000000003712

Raghavan Gopalakrishnan,Claire Sonneborn,Sylvain Baillet,Andre G Machado,Tor D Wager,Mathieu Roy

{"title":"Neurophysiological encoding of aversive prediction errors.","authors":"Raghavan Gopalakrishnan,Claire Sonneborn,Sylvain Baillet,Andre G Machado,Tor D Wager,Mathieu Roy","doi":"10.1097/j.pain.0000000000003712","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003712","url":null,"abstract":"Aversive prediction error (PE) brain signals generated by unexpected pain or pain absence are crucial for learning to avoid future pain. Yet, the detailed neurophysiological origins of PE signaling remain unclear. In this study, we combined an instrumental pain avoidance task with computational modeling and magnetoencephalography to detect time-resolved activations underlying pain expectations and aversive PE signals in the human brain. The task entailed learning probabilistically changing cue-pain associations to avoid receiving a pain stimulus. We used an axiomatic approach to identify general aversive PE signals that encode the degree to which the outcome deviated from expectations. Our findings indicate that aversive PE signals are generated in the alpha band (8-12 Hz) by the midbrain/diencephalon, lateral orbitofrontal cortex, and ventrolateral prefrontal cortex approximately 150 milliseconds after outcome delivery. Moreover, alpha oscillations in these regions also encoded pain expectations before the outcome. We speculate that this may facilitate the rapid generation of PEs by allowing outcome-related nociceptive activity to be integrated with ongoing predictive signals. Finally, decisions to avoid pain recruited alpha oscillations in the anterior cingulate and dorsomedial prefrontal cortices, suggesting their active engagement in comparing predicted action values. Overall, our data reveal the rapid neurophysiological mechanisms underlying the generation of aversive PEs and subsequent decision-making.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"104 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639737","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

STIM1 functionally couples to transient receptor potential ankyrin 1 contributing to nociception. STIM1在功能上与瞬时受体电位锚蛋白1偶联，参与伤害感受。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-16 DOI: 10.1097/j.pain.0000000000003729

Yixiao Mei,Hareram Birla,Bo Hyun Lee,Zhixiao Li,Vipin Rai,Isis Zhang,Xiaodong Huo,Anni Yi,Qiao Zhang,Daling Li,Yu Zhong,Fengying Wang,Bushra Yasin,Carol Apai,Tibor Rohacs,Yuan-Xiang Tao,Alex Bekker,Huijuan Hu

{"title":"STIM1 functionally couples to transient receptor potential ankyrin 1 contributing to nociception.","authors":"Yixiao Mei,Hareram Birla,Bo Hyun Lee,Zhixiao Li,Vipin Rai,Isis Zhang,Xiaodong Huo,Anni Yi,Qiao Zhang,Daling Li,Yu Zhong,Fengying Wang,Bushra Yasin,Carol Apai,Tibor Rohacs,Yuan-Xiang Tao,Alex Bekker,Huijuan Hu","doi":"10.1097/j.pain.0000000000003729","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003729","url":null,"abstract":"STIM1 is a calcium sensor that can sense calcium level changes in the endoplasmic reticulum (ER) and respond to extracellular stimuli. We have reported that STIM1 is expressed in nociceptors. However, its functional significance remains unclear. Here, we show that STIM1 plays an important role in sensing cold, chemical, and noxious mechanical stimuli in both male and female mice. We found that activation of transient receptor potential ankyrin 1 (TRPA1) triggers ER Ca2+ release, STIM1 translocation, and store-operated Ca2+ entry (SOCE). Immunostaining and western blot results reveal that TRPA1 is expressed in the ER. In addition, STIM1 deficiency in the primary sensory neurons reduces cold-, allyl isothiocyanate (TRPA1 agonist)-, and bradykinin-induced Ca2+ entry and nociception. Moreover, intraplantar injection of thapsigargin, an ER Ca2+-ATPase inhibitor, evokes nociception and increases pain hypersensitivity, which is significantly attenuated in STIM1 conditional knockout or L3/L4 dorsal root ganglia STIM1 knockdown mice. Mechanistic studies demonstrate that STIM1-mediated SOCE increases neuronal excitability and decreases potassium channel Kv4-mediated outward currents in small to medium-sized dorsal root ganglion neurons, which is abolished by inhibiting the mitogen-activated protein kinase/extracellular receptor kinase pathway. Our findings demonstrate that STIM1 acts as a transducer of nociception and uncover a novel link between STIM1 and TRPA1ER. Our study also provides new insights into TRPA1-mediated nociception.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639738","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

Quantitative sensory testing for detecting small fiber impairment-the same old story or finally evidence-based decision making? 定量感官测试用于检测小纤维损伤——还是老故事还是最终基于证据的决策？

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-14 DOI: 10.1097/j.pain.0000000000003686

Elena K Enax-Krumova

引用次数: 0

Androgen levels and experimental pain sensitivity in healthy young adolescent girls. 健康青春期少女的雄激素水平与实验性疼痛敏感性

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-11 DOI: 10.1097/j.pain.0000000000003704

Gourav Banerjee,Joel Brown,Alana McMichael,Arbi Ben Abdallah,Sarah Buday,Thomas J Baranski,Simon Haroutounian,Deanna Barch,Jacob AuBuchon,Hadas Nahman-Averbuch

{"title":"Androgen levels and experimental pain sensitivity in healthy young adolescent girls.","authors":"Gourav Banerjee,Joel Brown,Alana McMichael,Arbi Ben Abdallah,Sarah Buday,Thomas J Baranski,Simon Haroutounian,Deanna Barch,Jacob AuBuchon,Hadas Nahman-Averbuch","doi":"10.1097/j.pain.0000000000003704","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003704","url":null,"abstract":"Androgens, such as testosterone, have an antinociceptive effect based on animal and adult studies. However, because androgens may exert different physiological effects during puberty, it is not clear whether the antinociceptive effect would also be found in adolescents. Thus, this study examined the relationships between testosterone levels and experimental pain sensitivity in healthy young adolescent girls. In addition, the relationships between experimental pain sensitivity and other androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone, and androstenedione, were explored, and the role of puberty in moderating these relationships was tested. Forty-five healthy girls (11.91 ± 1.35 years) completed comprehensive psychophysical assessments of heat, cold, and pressure pain thresholds, heat and cold pain intensity ratings, temporal summation, heat- and pressure-conditioned pain modulation, offset analgesia, and cold pain tolerance. Blood samples were collected to analyze sex hormone levels. Participants also completed the Pubertal Developmental Scale. Correlations and regression models examined the associations between androgens and experimental pain sensitivity, and whether pubertal stage moderated these relationships. Overall, no significant associations were found between levels of testosterone, DHEA, DHEA-S, dihydrotestosterone, or androstenedione and experimental pain sensitivity, nor were these associations moderated by pubertal stage. Only DHEA-S levels were related to cold pain threshold and tolerance, and pubertal stage moderated the relationship between DHEA-S and cold pain tolerance, which was significant only in the late (r = 0.453, P = 0.027) but not early-mid puberty group. The results of this study suggest that androgens may have a minimal effect on experimental pain sensitivity in healthy young adolescent girls.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"8 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639837","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

Peripheral contributions to offset analgesia: effects of stimulus duration, intensity, and location. 外周对抵消性镇痛的贡献：刺激持续时间、强度和位置的影响。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-11 DOI: 10.1097/j.pain.0000000000003745

Pengyuan Sun,Alvin P H Wong,Christopher L Asplund,Stuart W G Derbyshire

{"title":"Peripheral contributions to offset analgesia: effects of stimulus duration, intensity, and location.","authors":"Pengyuan Sun,Alvin P H Wong,Christopher L Asplund,Stuart W G Derbyshire","doi":"10.1097/j.pain.0000000000003745","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003745","url":null,"abstract":"Offset analgesia (OA) is a substantial decrease in pain perception after a minor reduction in noxious stimulus intensity. The peripheral mechano- and heat-sensitive A-fibre nociceptors (AMH-I and AMH-II) and the C-fibre nociceptors (CMH) are hypothesised to contribute to OA. These nociceptors differ in initial response latency, peak response latency, and heat threshold, and the AMH-II fibres may be absent from the palm. Stimuli targeting those different nociceptive properties were used to decide which nociceptors critically contribute to OA. Healthy volunteers (N = 64) underwent 16 unique trials with continuous noxious heat (45-47°C). These trials included 3-second (short) or 12-second (long) periods of increased noxious heat (46-48°C), or an intense 0.2 seconds pulse of heat (51°C). Stimuli were delivered to the dorsum (back) and palm of the hands. Notable OA effects were observed for long-duration trials on both the dorsum and palm of the hand. Offset analgesia was inconsistently present and much smaller for the short-duration trials and for the pulse trials. Pain ratings generally increased more slowly during palm stimulation compared with dorsum stimulation. The demonstration of OA on the palm suggests that AMH-II nociceptors are either not critical for OA or that the AMH-II nociceptors are present in the palm. The small OA after the intense pulse and the substantial reduction in OA during the short trials suggests that AMH-I nociceptors are not necessary for OA and that the faster response of the AMH-II or CMH nociceptors is not sufficient to generate OA.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"8 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639842","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

Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use. 慢性疼痛和长期阿片类药物使用与人脊髓背角KCC2表达降低有关。

IF 5.9 1区医学

PAIN® Pub Date : 2025-07-11 DOI: 10.1097/j.pain.0000000000003700

Olivia C Davis, Samuel Ferland, Louis-Etienne Lorenzo, Clare Murray-Lawson, Stephanie Shiers, Muhammad Saad Yousuf, Annemarie Dedek, Eve C Tsai, Erin Vines, Peter Horton, Anna Cervantes, Tariq Khan, Geoffrey Funk, Gregory Dussor, Antoine G Godin, Francesco Ferrini, Yves De Koninck, Michael E Hildebrand, Theodore J Price

{"title":"Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use.","authors":"Olivia C Davis, Samuel Ferland, Louis-Etienne Lorenzo, Clare Murray-Lawson, Stephanie Shiers, Muhammad Saad Yousuf, Annemarie Dedek, Eve C Tsai, Erin Vines, Peter Horton, Anna Cervantes, Tariq Khan, Geoffrey Funk, Gregory Dussor, Antoine G Godin, Francesco Ferrini, Yves De Koninck, Michael E Hildebrand, Theodore J Price","doi":"10.1097/j.pain.0000000000003700","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003700","url":null,"abstract":"<p><strong>Abstract: </strong>Loss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here, we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643152","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

12/15-lipoxygenases mediate toll-like receptor 4-dependent nociplastic pain hypersensitivity in female mice. 12/15-脂氧合酶介导雌性小鼠toll样受体4依赖性致伤性疼痛超敏反应。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-10 DOI: 10.1097/j.pain.0000000000003711

Cristina Miliano,Irene Chen,Brieann Brown,Laura B Murdaugh,Yuyang Dong,Kelly A Eddinger,Shuo Geng,Liwu Li,Tony L Yaksh,Michael D Burton,Matthew W Buczynski,Ann M Gregus

{"title":"12/15-lipoxygenases mediate toll-like receptor 4-dependent nociplastic pain hypersensitivity in female mice.","authors":"Cristina Miliano,Irene Chen,Brieann Brown,Laura B Murdaugh,Yuyang Dong,Kelly A Eddinger,Shuo Geng,Liwu Li,Tony L Yaksh,Michael D Burton,Matthew W Buczynski,Ann M Gregus","doi":"10.1097/j.pain.0000000000003711","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003711","url":null,"abstract":"Chronic nociplastic pain syndromes are characterized by sensitization of peripheral and central nervous systems and exhibit increased incidence in women. However, nonsteroidal anti-inflammatory drugs are ineffective in mitigating nociplastic pain, and current prescription treatments, such as opioids, anticonvulsants, and antidepressants, provide limited therapeutic benefit for these indications. In the current work, we extended previous studies in rats of central Toll-like receptor 4-dependent pain hypersensitivity to male and female C57BL/6N mice, uncovering an unexpected hyperalgesic phenotype in female mice following intrathecal (IT) lipopolysaccharide (LPS). In contrast to previous reports in female C57BL/6J mice, female C57BL/6N mice displayed tactile and cold allodynia, grip force deficits, and a modest increase in locomotor activity in response to IT LPS. Congruent with our previous observations in male rats, LPS released spinal 12/15-lipoxygenase (12/15-LOX) metabolites (12/15-LMs) in female C57BL/6N mice. Likewise, 12/15-LOX enzymes are basally expressed in multiple tissues and cell types relevant to nociceptive transmission. Systemic inhibition of 12/15-LOX in female C57BL/6N mice with selective inhibitors ML355 (targeting 12-LOX-p) or ML351 (targeting 15-LOX-1) completely reversed allodynia and grip force deficits. 12/15-LMs also produce tactile allodynia when administered spinally (IT) or peripherally (paw intraplantar) at a subthreshold dose in a hyperalgesic priming model, similar to others' observations with a subthreshold dose of the cyclooxygenase metabolite prostaglandin E2. Collectively, these data suggest that 12/15-LOX enzymes contribute to peripheral and central pain hypersensitivity in rodents, with potential translatability as druggable targets across sexes and species using multiple reflexive and functional outcome measures.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"4 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639838","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

Diminished transient receptor vanilloid 1 on skin nerve fibers in painful bortezomib-induced peripheral neuropathy. 疼痛性硼替佐米诱导的周围神经病变中皮肤神经纤维瞬时受体香草样蛋白1的减少。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-07 DOI: 10.1097/j.pain.0000000000003709

Yuying Jin,Aishwarya Aravamudhan,Nadine Cebulla,Daniel Schirmer,Eva Runau,Leon Flamm,Calvin Terhorst,Laura Jähnel,Johanna Güse,Nicola Giordani,Annett Wieser,Annemarie Sodmann,Robert Blum,Robert J Kittel,Claudia Sommer

{"title":"Diminished transient receptor vanilloid 1 on skin nerve fibers in painful bortezomib-induced peripheral neuropathy.","authors":"Yuying Jin,Aishwarya Aravamudhan,Nadine Cebulla,Daniel Schirmer,Eva Runau,Leon Flamm,Calvin Terhorst,Laura Jähnel,Johanna Güse,Nicola Giordani,Annett Wieser,Annemarie Sodmann,Robert Blum,Robert J Kittel,Claudia Sommer","doi":"10.1097/j.pain.0000000000003709","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003709","url":null,"abstract":"Bortezomib-induced peripheral neuropathy (BIPN) is frequently accompanied by reduced thermal sensation and neuropathic pain. We explored the relation between transient receptor vanilloid 1 (TRPV1) receptors on skin nerves and BIPN pain. We combined PGP9.5 and TRPV1 immunofluorescence labelling on skin biopsy sections from 67 individuals, 27 patients with BIPN without pain, 18 patients with BIPN with pain, and 22 healthy volunteers. A total of 332 bioimages were collected and quantified using objective image analysis. qPCR was used to measure TRPV1 mRNA in the skin. Quantitative sensory testing and pain questionnaires were used to gather clinical data. Transient receptor vanilloid 1 immunoreactivity appeared as distinct puncta along the nerve fibers. Its normalized mean fluorescence intensity (TRPV1/PGP9.5 MFI) (P < 0.05) and TRPV1 puncta area (P < 0.001) were decreased in small nerve fibers of patients with BIPN, concomitantly with reduced thermal sensitivity. Further stratification based on pain symptoms demonstrated a greater reduction in TRPV1/PGP9.5 MFI and severe impairment in thermal difference detection ability (TSL) and heat pain thresholds (HPT) in painful BIPN. Pain levels were negatively correlated with TRPV1/PGP9.5 MFI in the epidermis and subepidermis (P < 0.001 r = -0.44; P < 0.001, r = -0.42), and with z-scores of TSL and HPT (P < 0.05; P < 0.05). Transient receptor vanilloid 1 mRNA levels in skin were not different between groups, indicating that cellular synthesis of TRPV1 was not altered. Diminished TRPV1 immunoreactivity on nerves of patients with BIPN with pain aligns with their insensitivity to thermal stimuli which may help to better understand the pathophysiology of pain in patients with BIPN.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"9 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578531","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

Spinal disk injury induces germinal center formation, pronociceptive antibody production, and chronic nociceptive sensitization in a male mouse back pain model. 在雄性小鼠背部疼痛模型中，椎间盘损伤诱导生发中心形成、原感觉抗体产生和慢性伤害性致敏。

IF 7.4 1区医学

PAIN® Pub Date : 2025-07-07 DOI: 10.1097/j.pain.0000000000003706

Tzuping Wei,Tian-Zhi Guo,Xiaoyou Shi,Wen-Wu Li,J David Clark,Wade S Kingery

{"title":"Spinal disk injury induces germinal center formation, pronociceptive antibody production, and chronic nociceptive sensitization in a male mouse back pain model.","authors":"Tzuping Wei,Tian-Zhi Guo,Xiaoyou Shi,Wen-Wu Li,J David Clark,Wade S Kingery","doi":"10.1097/j.pain.0000000000003706","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003706","url":null,"abstract":"Accumulating evidence suggests that spinal intervertebral disk damage is associated with activation of the adaptive immune system. Key unknown features of this response are the mechanism and time course for the generation of pronociceptive antibodies and the antibody classes involved. This study used the lumbar spinal disk puncture (DP) model in male wildtype (WT) and muMT mice (lacking mature B cells) to evaluate pronociceptive immune responses. Sera collected up to 33 weeks after DP were purified for immunoglobulin (Ig)M and IgG intrathecal injections and antigen binding experiments. Spinal cords and disks were collected for quantitative polymerase chain reaction, western, and immunohistochemical analyses. Disk puncture injury in muMT mice had minimal effect, but in WT mice, it induced hindpaw allodynia, hyperalgesia, and grip weakness that gradually resolved after 6 months. Spinal cord expression of inflammatory cytokines and complement components was chronically upregulated after DP, peaking at 1 to 3 weeks. Increased IgM and IgG autoantigen binding and deposition in the spinal cord peaked at 10 to 20 weeks after DP injury. Lumbar lymph node immunostaining demonstrated B-cell germinal center formation beginning at 3 weeks and peaking at 10 to 20 weeks after DP injury. Intrathecal injection of IgM and IgG collected between 3 and 20 weeks after DP in WT mice was pronociceptive in muMT DP mice. Preemptive pharmacologic intervention targeting B cells had no effect on early nociceptive sensitization but reduced sensitization when administered at 10 weeks after DP injury in WT mice. Collectively, these data support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain state.","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"32 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578768","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