Neurobiology of Pain最新文献_第2页

The impact of nerve injury on the immune system across the lifespan is sexually dimorphic 神经损伤对免疫系统的影响在整个生命周期中是两性二态的

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-08-20 DOI: 10.1016/j.ynpai.2025.100195

Wen Bo S. Zhou , Xiang Q. Shi , Alain P. Zhang , Magali Millecamps , Jeffrey S. Mogil , Ji Zhang

Although nerve injury-associated neuroinflammation contributes to neuropathic pain, the long-term impact of such injury on systemic homeostasis and its potential role in pain remains elusive. In this study, we aim to understand the systemic changes that are present alongside chronic pain in nerve-injured male and female mice across their lifespan. We monitored mechanical and cold sensitivity in male and female mice starting at the age of 3–4 months old when they received spared nerve injury (SNI), up to 20-month post-injury. Alongside, we collected blood samples to track changes in immune cells with flow cytometry, and to assess inflammation-related serum proteome using a 111-target Proteome Profiler. We also transferred serum from sham/SNI mice to naïve mice to determine the potential of systemic contribution to pain. While nerve injury did not affect immune cell composition in the blood, it triggered a long-lasting disturbance of molecular profile in the serum of sham/SNI mice, in a sex-dependent manner. Compared to sham surgery, nerve injury amplified regulation of inflammatory proteins in males, but slightly reduced it in females. These changes in the serum occurred in parallel with long-lasting mechanical and cold hypersensitivity in the nerve-injured mice. Both male and female SNI serum induced hypersensitivity when transferred to naïve mice, regardless of a sex-matched or sex-mismatched transfer. Our results highlight that a local nerve injury can have persistent systemic impact. Injury-associated systemic inflammation could contribute to neuropathic pain, but the underlying mechanisms may be sexually dimorphic.

尽管神经损伤相关的神经炎症有助于神经性疼痛，但这种损伤对全身稳态的长期影响及其在疼痛中的潜在作用仍然难以捉摸。在这项研究中，我们旨在了解神经损伤的雄性和雌性小鼠在其整个生命周期中伴随慢性疼痛而出现的系统性变化。我们监测了雄性和雌性小鼠的机械和冷敏感性，从3-4个月大开始，当它们接受了神经损伤（SNI），直到损伤后20个月。此外，我们收集血液样本，用流式细胞术跟踪免疫细胞的变化，并使用111靶点蛋白质组分析器评估炎症相关的血清蛋白质组。我们还将假手术/SNI小鼠的血清转移到naïve小鼠身上，以确定全身对疼痛的潜在贡献。虽然神经损伤不影响血液中的免疫细胞组成，但它会以性别依赖的方式引发sham/SNI小鼠血清中分子谱的长期紊乱。与假手术相比，神经损伤放大了雄性炎症蛋白的调节，但在雌性中略有降低。血清中的这些变化与神经损伤小鼠的长期机械和冷超敏反应同时发生。无论性别匹配还是性别不匹配，雄性和雌性SNI血清在转移到naïve小鼠时均引起超敏反应。我们的结果强调，局部神经损伤可以有持续的全身性影响。损伤相关的全身性炎症可能导致神经性疼痛，但潜在的机制可能是两性二态的。

{"title":"The impact of nerve injury on the immune system across the lifespan is sexually dimorphic","authors":"Wen Bo S. Zhou , Xiang Q. Shi , Alain P. Zhang , Magali Millecamps , Jeffrey S. Mogil , Ji Zhang","doi":"10.1016/j.ynpai.2025.100195","DOIUrl":"10.1016/j.ynpai.2025.100195","url":null,"abstract":"<div><div>Although nerve injury-associated neuroinflammation contributes to neuropathic pain, the long-term impact of such injury on systemic homeostasis and its potential role in pain remains elusive. In this study, we aim to understand the systemic changes that are present alongside chronic pain in nerve-injured male and female mice across their lifespan. We monitored mechanical and cold sensitivity in male and female mice starting at the age of 3–4 months old when they received spared nerve injury (SNI), up to 20-month post-injury. Alongside, we collected blood samples to track changes in immune cells with flow cytometry, and to assess inflammation-related serum proteome using a 111-target Proteome Profiler. We also transferred serum from sham/SNI mice to naïve mice to determine the potential of systemic contribution to pain. While nerve injury did not affect immune cell composition in the blood, it triggered a long-lasting disturbance of molecular profile in the serum of sham/SNI mice, in a sex-dependent manner. Compared to sham surgery, nerve injury amplified regulation of inflammatory proteins in males, but slightly reduced it in females. These changes in the serum occurred in parallel with long-lasting mechanical and cold hypersensitivity in the nerve-injured mice. Both male and female SNI serum induced hypersensitivity when transferred to naïve mice, regardless of a sex-matched or sex-mismatched transfer. Our results highlight that a local nerve injury can have persistent systemic impact. Injury-associated systemic inflammation could contribute to neuropathic pain, but the underlying mechanisms may be sexually dimorphic.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nrxn3 reduces myofascial nociceptive pain Nrxn3减轻肌筋膜痛觉性疼痛

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-09-08 DOI: 10.1016/j.ynpai.2025.100197

Lauren Nguyen, Mikhail Umorin, Phillip R. Kramer

Neurexin 3 (Nrxn3) has a role in neuronal signaling. Previous reports indicated that reducing Nrxn3 expression in the central amygdala increased orofacial neuropathic pain. A common temporomandibular disorder is myofascial pain. Thus, we hypothesized that Nrxn3 would reduce myofascial hypersensitivity. To test this hypothesis Nrxn3 shRNA was infused into the central amygdala of male rats. Then a ligature of the tendon attachment of the anterior superficial portion of the masseter muscle was performed to induce inflammatory orofacial pain. Dark phase meal duration was measured continuously, and von Frey filament testing was completed every 7 days for 21 days to measure the nociceptive response. After testing tissues were collected and the amount of Nrxn3 was measured. Neuronal activity in the orofacial pain pathway was quantitated by c-Fos staining of the central amygdala, lateral parabrachial nucleus, trigeminal ganglia and trigeminal nucleus caudalis. Knockdown of Nrxn3 in the central amygdala significantly increased the pain response and increased the levels of c-Fos. This increased response was observed for greater than two weeks. The data suggests Nrxn3 expression within the central amygdala attenuates nociceptive orofacial pain by reducing neuronal activity.

Neurexin 3 （Nrxn3）在神经元信号传导中起作用。先前的报道表明，减少中央杏仁核中Nrxn3的表达会增加口面部神经性疼痛。常见的颞下颌疾病是肌筋膜疼痛。因此，我们假设Nrxn3可以减少肌筋膜过敏。为了验证这一假设，我们将Nrxn3 shRNA注入雄性大鼠的中央杏仁核。然后对咬肌前浅表部分的肌腱连接进行结扎，以诱导炎症性口面部疼痛。连续测量暗相进食时间，每隔7天进行von Frey细丝测试，连续21天测量伤害反应。试验结束后，收集组织，测定Nrxn3的含量。采用c-Fos染色法对中央杏仁核、外侧臂旁核、三叉神经节和三叉尾核进行定量分析。中枢杏仁核中Nrxn3的下调显著增加了疼痛反应，并增加了c-Fos水平。观察到这种增加的反应超过两周。数据表明，中央杏仁核内Nrxn3的表达通过减少神经元活动来减轻伤害性口面部疼痛。

{"title":"Nrxn3 reduces myofascial nociceptive pain","authors":"Lauren Nguyen, Mikhail Umorin, Phillip R. Kramer","doi":"10.1016/j.ynpai.2025.100197","DOIUrl":"10.1016/j.ynpai.2025.100197","url":null,"abstract":"<div><div>Neurexin 3 (Nrxn3) has a role in neuronal signaling. Previous reports indicated that reducing Nrxn3 expression in the central amygdala increased orofacial neuropathic pain. A common temporomandibular disorder is myofascial pain. Thus, we hypothesized that Nrxn3 would reduce myofascial hypersensitivity. To test this hypothesis Nrxn3 shRNA was infused into the central amygdala of male rats. Then a ligature of the tendon attachment of the anterior superficial portion of the masseter muscle was performed to induce inflammatory orofacial pain. Dark phase meal duration was measured continuously, and von Frey filament testing was completed every 7 days for 21 days to measure the nociceptive response. After testing tissues were collected and the amount of Nrxn3 was measured. Neuronal activity in the orofacial pain pathway was quantitated by c-Fos staining of the central amygdala, lateral parabrachial nucleus, trigeminal ganglia and trigeminal nucleus caudalis. Knockdown of Nrxn3 in the central amygdala significantly increased the pain response and increased the levels of c-Fos. This increased response was observed for greater than two weeks. The data suggests Nrxn3 expression within the central amygdala attenuates nociceptive orofacial pain by reducing neuronal activity.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Humanized NaV1.8 rats overcome cross-species potency shifts in developing novel NaV1.8 inhibitors 人源化的NaV1.8大鼠在开发新型NaV1.8抑制剂时克服了跨物种的效力变化

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-03-06 DOI: 10.1016/j.ynpai.2025.100182

Dillon S. McDevitt , Joshua D. Vardigan , Xiaoping Zhou , Thomas W. Rosahl , Heather Zhou , Eric A. Price , Michelle K. Clements , Yuxing Li , Nissi Varghese , Alicja Krasowska-Zoladek , Shawn J. Stachel , Michael J. Breslin , Christopher S. Burgey , Richard L. Kraus , Parul S. Pall , Darrell A. Henze , Vincent P. Santarelli

Voltage-gated sodium channel isoform 1.8 (Na_V1.8) has emerged as a promising pharmaceutical target for the treatment of acute and chronic pain. However, highly selective and potent inhibitors for this channel have been difficult to develop and only recently have advanced to clinical testing. Our efforts to develop Na_V1.8 small molecule inhibitors yielded a series of molecules with favorable in vitro potency and selectivity against the human Na_V1.8 channel but exhibited dramatic rightward potency shifts against the rodent channel, severely limiting in vivo screening and candidate selection. In anticipation of supporting drug discovery efforts, a transgenic rat line expressing the human Na_V1.8 channel in lieu of the rodent channel was developed. Utilizing these humanized animals, the in vitro potency of our chemical matter in freshly isolated humanized rat DRG neurons was consistent with in vitro human potency values, enabling in vivo work to progress. We demonstrate capsaicin-induced nocifensive behaviors (CNB) as a moderate throughput in vivo screening assay, from which we demonstrate pharmacokinetic-pharmacodynamic (PK-PD) and in vitro-in vivo correlation (IVIVC) relationships. We identified MSD199 as a potent Na_V1.8 inhibitor with acute pain efficacy and assessed it in traditional inflammatory (Complete Freund’s Adjuvant) and neuropathic (spinal nerve ligation) behavioral chronic pain assays where it was shown to significantly reduce pain-related behaviors. Overall, we demonstrate the utility of humanized transgenic animals when cross-species potency shifts are observed within an otherwise promising chemical series.

电压门控钠通道异构体1.8 （NaV1.8）已成为治疗急慢性疼痛的一个有前途的药物靶点。然而，这一通道的高选择性和强效抑制剂一直难以开发，直到最近才进入临床试验阶段。我们努力开发的NaV1.8小分子抑制剂产生了一系列对人类NaV1.8通道具有良好的体外效力和选择性的分子，但对啮齿动物通道表现出明显的右移效力，严重限制了体内筛选和候选物的选择。为了支持药物发现工作，开发了一种表达人类NaV1.8通道的转基因大鼠系来代替啮齿动物通道。利用这些人源化动物，我们的化学物质在新分离的人源化大鼠DRG神经元中的体外效力值与体外人效力值一致，使体内工作得以进行。我们证明了辣椒素诱导的有害行为（CNB）是一种中等通量的体内筛选试验，从中我们证明了药代动力学-药效学（PK-PD）和体外-体内相关（IVIVC）关系。我们确定MSD199是一种有效的NaV1.8抑制剂，具有急性疼痛疗效，并在传统的炎症（完全弗氏佐剂）和神经性（脊神经结扎）行为慢性疼痛试验中对其进行了评估，结果显示，MSD199可显著减少疼痛相关行为。总的来说，我们证明了当在其他有前途的化学系列中观察到跨物种效力变化时，人源化转基因动物的效用。

{"title":"Humanized NaV1.8 rats overcome cross-species potency shifts in developing novel NaV1.8 inhibitors","authors":"Dillon S. McDevitt , Joshua D. Vardigan , Xiaoping Zhou , Thomas W. Rosahl , Heather Zhou , Eric A. Price , Michelle K. Clements , Yuxing Li , Nissi Varghese , Alicja Krasowska-Zoladek , Shawn J. Stachel , Michael J. Breslin , Christopher S. Burgey , Richard L. Kraus , Parul S. Pall , Darrell A. Henze , Vincent P. Santarelli","doi":"10.1016/j.ynpai.2025.100182","DOIUrl":"10.1016/j.ynpai.2025.100182","url":null,"abstract":"<div><div>Voltage-gated sodium channel isoform 1.8 (Na<sub>V</sub>1.8) has emerged as a promising pharmaceutical target for the treatment of acute and chronic pain. However, highly selective and potent inhibitors for this channel have been difficult to develop and only recently have advanced to clinical testing. Our efforts to develop Na<sub>V</sub>1.8 small molecule inhibitors yielded a series of molecules with favorable <em>in vitro</em> potency and selectivity against the human Na<sub>V</sub>1.8 channel but exhibited dramatic rightward potency shifts against the rodent channel, severely limiting <em>in vivo</em> screening and candidate selection. In anticipation of supporting drug discovery efforts, a transgenic rat line expressing the human Na<sub>V</sub>1.8 channel in lieu of the rodent channel was developed. Utilizing these humanized animals, the <em>in vitro</em> potency of our chemical matter in freshly isolated humanized rat DRG neurons was consistent with <em>in vitro</em> human potency values, enabling <em>in vivo</em> work to progress. We demonstrate capsaicin-induced nocifensive behaviors (CNB) as a moderate throughput <em>in vivo</em> screening assay, from which we demonstrate pharmacokinetic-pharmacodynamic (PK-PD) and <em>in vitro</em>-<em>in vivo</em> correlation (IVIVC) relationships. We identified MSD199 as a potent Na<sub>V</sub>1.8 inhibitor with acute pain efficacy and assessed it in traditional inflammatory (Complete Freund’s Adjuvant) and neuropathic (spinal nerve ligation) behavioral chronic pain assays where it was shown to significantly reduce pain-related behaviors. Overall, we demonstrate the utility of humanized transgenic animals when cross-species potency shifts are observed within an otherwise promising chemical series.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Voluntary exercise prevents and eradicates anxiety-like behavior by influencing parvalbumin-positive neurons, perineuronal nets, and microglia activation in corticolimbic regions of neuropathic pain rats 自愿运动通过影响神经性疼痛大鼠皮质边缘区的小蛋白阳性神经元、神经周围网和小胶质细胞激活来预防和根除焦虑样行为

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-02-27 DOI: 10.1016/j.ynpai.2025.100181

Thu Nguyen Dang , Cuong Nguyen Van , Ryosuke Ochi , Hiroki Kuwamura , Tomoyuki Kurose , Yoki Nakamura , Kazue Hisaoka-Nakashima , Norimitsu Morioka , Hisao Nishijo , Naoto Fujita , Susumu Urakawa

Anxiety-like behavior often emerges in the later stages of neuropathic pain, exacerbating the pain condition and potentially involving parvalbumin-positive (PV⁺) neurons. This study aimed to investigate the effects of voluntary exercise on neuropathic pain-induced anxiety and its relationship with PV⁺ neurons, perineuronal nets (PNNs, labeled with Wisteria floribunda agglutinin [WFA]), and microglia in the corticolimbic regions. Male Wistar rats with partial sciatic nerve ligation (PSL) were given access to running wheels either from 3 days (early voluntary exercise [EEx]) or from 4 weeks (late voluntary exercise [LEx]) postoperatively. Nociceptive behaviors were assessed using the von Frey and acetone tests, while anxiety-like behaviors were assessed using the open field and elevated plus maze tests. Brain sections were histologically analyzed using immunohistochemistry and immunofluorescence 8 weeks post-surgery. Both early and late exercise partially restored the paw withdrawal thresholds and the arousal response. PSL-EEx rats did not exhibit anxiety-like behaviors. PSL-LEx rats transiently showed anxiety-like behaviors, but these were eradicated by exercise. PSL altered PV⁺ neurons and PNNs in specific corticolimbic subregions. Notably, voluntary exercise restored the densities of PV⁺-strong WFA⁺ neurons in the basolateral amygdala, PV⁺-WFA^-, and PV⁺-WFA⁺ neurons in the anterior cingulate cortex, and PV⁺-WFA⁺ neurons in the hippocampal cornu ammonis 1. These changes correlated with reduced anxiety-like behaviors. Exercise modulated PSL-induced microglial activation and interacted differently with these neurons. These findings suggest that voluntary exercise prevents and eliminates chronic pain-induced anxiety through neuronal mechanisms other than analgesic effects, potentially involving PV⁺ neurons, PNNs, and microglia in the corticolimbic subregions.

焦虑样行为通常出现在神经性疼痛的后期，加剧疼痛状况，并可能涉及小蛋白阳性（PV+）神经元。本研究旨在探讨自主运动对神经性疼痛性焦虑的影响及其与皮质边缘区PV+神经元、周围神经元网（PNNs，标记有紫藤凝集素[WFA]）和小胶质细胞的关系。部分坐骨神经结扎（PSL）的雄性Wistar大鼠术后3天（早期自愿运动[EEx]）或4周（晚期自愿运动[LEx]）给予滚轮活动。伤害性行为采用von Frey和丙酮测试进行评估，而焦虑样行为采用开阔场和升高加迷宫测试进行评估。术后8周采用免疫组织化学和免疫荧光对脑切片进行组织学分析。早、晚运动均能部分恢复足爪退缩阈值和唤醒反应。PSL-EEx大鼠没有表现出焦虑样行为。PSL-LEx大鼠短暂表现出焦虑样行为，但这些行为通过运动消除。PSL改变了特定皮质边缘亚区PV+神经元和pnn。值得注意的是，自愿运动恢复了基底外侧杏仁核PV+-强WFA+神经元、前扣带皮层PV+-WFA-和PV+-WFA+神经元以及海马海马角的PV+-WFA+神经元的密度1。这些变化与减少焦虑行为有关。运动调节psl诱导的小胶质细胞激活，并与这些神经元发生不同的相互作用。这些发现表明，自愿运动通过非镇痛作用的神经元机制预防和消除慢性疼痛引起的焦虑，可能涉及皮质边缘亚区的PV+神经元、PNNs和小胶质细胞。

{"title":"Voluntary exercise prevents and eradicates anxiety-like behavior by influencing parvalbumin-positive neurons, perineuronal nets, and microglia activation in corticolimbic regions of neuropathic pain rats","authors":"Thu Nguyen Dang , Cuong Nguyen Van , Ryosuke Ochi , Hiroki Kuwamura , Tomoyuki Kurose , Yoki Nakamura , Kazue Hisaoka-Nakashima , Norimitsu Morioka , Hisao Nishijo , Naoto Fujita , Susumu Urakawa","doi":"10.1016/j.ynpai.2025.100181","DOIUrl":"10.1016/j.ynpai.2025.100181","url":null,"abstract":"<div><div>Anxiety-like behavior often emerges in the later stages of neuropathic pain, exacerbating the pain condition and potentially involving parvalbumin-positive (PV<sup>+</sup>) neurons. This study aimed to investigate the effects of voluntary exercise on neuropathic pain-induced anxiety and its relationship with PV<sup>+</sup> neurons, perineuronal nets (PNNs, labeled with Wisteria floribunda agglutinin [WFA]), and microglia in the corticolimbic regions. Male Wistar rats with partial sciatic nerve ligation (PSL) were given access to running wheels either from 3 days (early voluntary exercise [EEx]) or from 4 weeks (late voluntary exercise [LEx]) postoperatively. Nociceptive behaviors were assessed using the von Frey and acetone tests, while anxiety-like behaviors were assessed using the open field and elevated plus maze tests. Brain sections were histologically analyzed using immunohistochemistry and immunofluorescence 8 weeks post-surgery. Both early and late exercise partially restored the paw withdrawal thresholds and the arousal response. PSL-EEx rats did not exhibit anxiety-like behaviors. PSL-LEx rats transiently showed anxiety-like behaviors, but these were eradicated by exercise. PSL altered PV<sup>+</sup> neurons and PNNs in specific corticolimbic subregions. Notably, voluntary exercise restored the densities of PV<sup>+</sup>-strong WFA<sup>+</sup> neurons in the basolateral amygdala, PV<sup>+</sup>-WFA<sup>-</sup>, and PV<sup>+</sup>-WFA<sup>+</sup> neurons in the anterior cingulate cortex, and PV<sup>+</sup>-WFA<sup>+</sup> neurons in the hippocampal cornu ammonis 1. These changes correlated with reduced anxiety-like behaviors. Exercise modulated PSL-induced microglial activation and interacted differently with these neurons. These findings suggest that voluntary exercise prevents and eliminates chronic pain-induced anxiety through neuronal mechanisms other than analgesic effects, potentially involving PV<sup>+</sup> neurons, PNNs, and microglia in the corticolimbic subregions.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain aging among individuals with trigeminal neuralgia 三叉神经痛患者的脑老化

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-10-17 DOI: 10.1016/j.ynpai.2025.100201

Yenisel Cruz-Almeida , Pedro A. Valdes-Hernandez , Yun Liang , Mingzhou Ding , John K. Neubert

Trigeminal neuralgia (TN) is a complex orofacial neuropathic pain condition with limited understanding of underlying mechanisms and therapeutic options. Emerging evidence suggests the involvement of the brain in persons with TN including widespread brain changes when employing a widely used brain aging biomarker that estimates a predicted brain age difference or brain age gap. The aim of the present cross-sectional study was to assess the predicted brain age difference (brain-PAD) or brain age gap across two TN subtypes (classical TN, and secondary/idiopathic TN) in comparison with age-and sex-matched pain-free controls and its association with several clinical and psychological characteristics. Thirty-four individuals diagnosed with Classical TN, 17 diagnosed with secondary/idiopathic TN were age- and sex-matched to pain-free controls (n = 54). All participants underwent a T1 brain MRI and completed clinical and psychological measures. There were significant differences in brain-PAD among TN subtypes (ANCOVA p = 0.0078, effect size f² = 0.28²), with individuals diagnosed with Classical TN having a brain-PAD significantly greater than the controls by 3.87 years (p = 0.01, Bonferroni-corrected). There were no significant brain-PAD differences between secondary/idiopathic TN and pain-free controls. Brain-PAD had a significant positive association with both pain catastrophizing (p < 0.05) and pain-related anxiety (p < 0.05), but no significant association with disease duration (p < 0.05) or usual pain intensity (p < 0.05) in persons with classical TN. The results were similar using a second brain aging biomarker. We report here accelerated brain aging processes in individuals with classical TN, but not in persons diagnosed with secondary/idiopathic TN. Our study replicates previous findings and adds to the literature that accelerated brain aging may not occur across all TN subtypes. Given the increased use of MRI for TN diagnostics, combined with our own recent work deriving brain aging biomarkers from clinical-grade scans, future studies within clinical settings are feasible and may help understand this debilitating condition.

三叉神经痛（TN）是一种复杂的口面部神经性疼痛，对其潜在机制和治疗方案的了解有限。新出现的证据表明，当使用广泛使用的脑衰老生物标志物来估计预测的脑年龄差异或脑年龄差距时，TN患者的大脑参与其中，包括广泛的大脑变化。本横断面研究的目的是评估两种TN亚型（经典TN和继发性/特发性TN）与年龄和性别匹配的无痛对照相比的预测脑年龄差异（脑- pad）或脑年龄差距及其与若干临床和心理特征的关联。34例诊断为经典TN， 17例诊断为继发性/特发性TN，年龄和性别与无痛对照组匹配（n = 54）。所有参与者都进行了T1脑MRI检查，并完成了临床和心理测量。脑- pad在TN亚型间存在显著差异（ANCOVA p = 0.0078，效应量f2 = 0.282），诊断为经典TN的个体脑- pad显著高于对照组3.87年（p = 0.01， bonferroni校正）。继发性/特发性TN与无痛对照组之间脑- pad无显著差异。在经典TN患者中，脑- pad与疼痛灾难化（p < 0.05）和疼痛相关焦虑（p < 0.05）均有显著正相关，但与疾病持续时间（p < 0.05）或通常疼痛强度（p < 0.05）无显著关联。使用第二种脑老化生物标志物，结果相似。我们在此报告了经典TN个体的加速脑老化过程，而不是诊断为继发性/特发性TN的人。我们的研究重复了以前的发现，并补充了文献，即加速脑老化可能不会发生在所有TN亚型中。鉴于MRI在TN诊断中的使用越来越多，结合我们自己最近从临床级扫描中获得脑老化生物标志物的工作，未来在临床环境中的研究是可行的，可能有助于了解这种使人衰弱的疾病。

{"title":"Brain aging among individuals with trigeminal neuralgia","authors":"Yenisel Cruz-Almeida , Pedro A. Valdes-Hernandez , Yun Liang , Mingzhou Ding , John K. Neubert","doi":"10.1016/j.ynpai.2025.100201","DOIUrl":"10.1016/j.ynpai.2025.100201","url":null,"abstract":"<div><div>Trigeminal neuralgia (TN) is a complex orofacial neuropathic pain condition with limited understanding of underlying mechanisms and therapeutic options. Emerging evidence suggests the involvement of the brain in persons with TN including widespread brain changes when employing a widely used brain aging biomarker that estimates a predicted brain age difference or brain age gap. The aim of the present cross-sectional study was to assess the predicted brain age difference (brain-PAD) or brain age gap across two TN subtypes (classical TN, and secondary/idiopathic TN) in comparison with age-and sex-matched pain-free controls and its association with several clinical and psychological characteristics. Thirty-four individuals diagnosed with Classical TN, 17 diagnosed with secondary/idiopathic TN were age- and sex-matched to pain-free controls (n = 54). All participants underwent a T1 brain MRI and completed clinical and psychological measures. There were significant differences in brain-PAD among TN subtypes (ANCOVA p = 0.0078, effect size f<sup>2</sup> = 0.28<sup>2</sup>), with individuals diagnosed with Classical TN having a brain-PAD significantly greater than the controls by 3.87 years (p = 0.01, Bonferroni-corrected). There were no significant brain-PAD differences between secondary/idiopathic TN and pain-free controls. Brain-PAD had a significant positive association with both pain catastrophizing (p < 0.05) and pain-related anxiety (p < 0.05), but no significant association with disease duration (p < 0.05) or usual pain intensity (p < 0.05) in persons with classical TN. The results were similar using a second brain aging biomarker. We report here accelerated brain aging processes in individuals with classical TN, but not in persons diagnosed with secondary/idiopathic TN. Our study replicates previous findings and adds to the literature that accelerated brain aging may not occur across all TN subtypes. Given the increased use of MRI for TN diagnostics, combined with our own recent work deriving brain aging biomarkers from clinical-grade scans, future studies within clinical settings are feasible and may help understand this debilitating condition.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal physiology of amygdala neurons in the context of injury and pain 损伤和疼痛背景下杏仁核神经元的神经生理学

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-06-27 DOI: 10.1016/j.ynpai.2025.100190

Blesson K Paul, Maria Isabel Nunez-Ordaz, Joseph R. Samuel, Benedict J. Kolber

The amygdala integrates polymodal information including nociceptive stimuli. It is implicated as a key node in regulating both sensory-discriminative and emotional-affective aspects of pain and central sensitization. While central sensitization mechanisms in persistent pain are not completely understood, studying the neuronal properties exhibited by the amygdala neurons within their functional context, in this case, nociception, is important. Such studies can shed light on the behavior-modulating potential of the amygdala. In the last twenty years, multiple laboratories have begun the process of dissecting the cell-type specific activity involved in amygdala function. This review surveys these electrophysiological properties of neurons from different amygdala nuclei, cell types and circuitry studied so far, in the context of nociception and injury. A population-level accounting of these cell types provides greater insight into identifying specific targets to develop interventions for pain-mediated affective conditions.

杏仁核整合包括伤害性刺激在内的多模态信息。它被认为是调节疼痛和中枢敏化的感觉-辨别和情绪-情感方面的关键节点。虽然持续疼痛的中枢致敏机制尚不完全清楚，但研究杏仁核神经元在其功能背景下所表现出的神经元特性，在这种情况下，伤害感觉是很重要的。这样的研究可以阐明杏仁核的行为调节潜能。在过去的二十年中，多个实验室已经开始解剖杏仁核功能中涉及的细胞类型特异性活动的过程。本文综述了迄今为止研究的不同杏仁核神经元的电生理特性、细胞类型和电路，在伤害和损伤的背景下。这些细胞类型的人口水平核算提供了更大的洞察力，以确定特定的目标，以开发干预疼痛介导的情感条件。

引用次数: 0

Individual differences in cognitive performance under pain linked to region-specific alpha power modulations 疼痛下认知表现的个体差异与特定区域的能量调节有关

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-09-10 DOI: 10.1016/j.ynpai.2025.100196

Francesca Storey , Mariya Prokhorenko , Michael L. Keaser , Patrick Skippen , Andrew J. Furman , David A. Seminowicz , Ali Mazaheri

Chronic pain is associated with reduced cognitive function, potentially due to a diversion of cognitive resources to processing pain. However, reduced cognitive function during pain is not always consistently evidenced, perhaps due to individual differences in the attentional cost of pain processing. In the current electroencephalography investigation, we therefore examined differences in the top-down modulation of oscillatory activity in a cognitive task, between participants who performed better, and worse, during experimentally induced neuropathic-like pain. We employed a cross-modal attention task in which visual cues indicated whether participants needed to judge the visual orientation or discriminate the auditory pitch of an upcoming target. The visual and auditory targets were presented either simultaneously or individually, enabling us to assess the “cost” of having a distractor present in each modality. Participants engaged in the task under two conditions: prolonged pain via the capsaicin-heat pain model, and pain-free. Participants less “costed” by visual distraction during pain demonstrated a greater increase in alpha power (8–12 Hz) over frontal/central electrodes during pain. This may reflect inhibition of regions related to the processing of painful stimuli (somatosensory cortex), which could increase availability of resources to meet task-demands – a possible task-favouring pattern. In conclusion, our results support the notion that better cognitive function during pain is associated with a behavioral strategy.

慢性疼痛与认知功能下降有关，可能是由于认知资源转移到处理疼痛。然而，疼痛时认知功能的降低并不总是得到一致的证明，这可能是由于疼痛处理的注意成本的个体差异。因此，在当前的脑电图调查中，我们研究了在实验诱导的神经性疼痛中，表现较好和较差的参与者在认知任务中振荡活动自上而下调节的差异。我们采用了一个跨模态注意任务，在这个任务中，视觉线索指示参与者是否需要判断即将到来的目标的视觉方向或辨别听觉音调。视觉和听觉目标同时或单独呈现，使我们能够评估在每种模式中都有一个分心物的“成本”。参与者在两种情况下参与任务：通过辣椒素热疼痛模型延长疼痛和无痛。在疼痛期间，较少“花费”视觉分心的参与者表现出比额叶/中央电极更大的α功率（8-12赫兹）增加。这可能反映了与处理痛苦刺激相关的区域（体感皮层）受到抑制，这可能会增加资源的可用性，以满足任务需求——一种可能的任务偏好模式。总之，我们的研究结果支持这样的观点，即疼痛时更好的认知功能与行为策略有关。

{"title":"Individual differences in cognitive performance under pain linked to region-specific alpha power modulations","authors":"Francesca Storey , Mariya Prokhorenko , Michael L. Keaser , Patrick Skippen , Andrew J. Furman , David A. Seminowicz , Ali Mazaheri","doi":"10.1016/j.ynpai.2025.100196","DOIUrl":"10.1016/j.ynpai.2025.100196","url":null,"abstract":"<div><div>Chronic pain is associated with reduced cognitive function, potentially due to a diversion of cognitive resources to processing pain. However, reduced cognitive function during pain is not always consistently evidenced, perhaps due to individual differences in the attentional cost of pain processing. In the current electroencephalography investigation, we therefore examined differences in the top-down modulation of oscillatory activity in a cognitive task, between participants who performed better, and worse, during experimentally induced neuropathic-like pain. We employed a cross-modal attention task in which visual cues indicated whether participants needed to judge the visual orientation or discriminate the auditory pitch of an upcoming target. The visual and auditory targets were presented either simultaneously or individually, enabling us to assess the “cost” of having a distractor present in each modality. Participants engaged in the task under two conditions: prolonged pain via the capsaicin-heat pain model, and pain-free. Participants less “costed” by visual distraction during pain demonstrated a greater increase in alpha power (8–12 Hz) over frontal/central electrodes during pain. This may reflect inhibition of regions related to the processing of painful stimuli (somatosensory cortex), which could increase availability of resources to meet task-demands – a possible task-favouring pattern. In conclusion, our results support the notion that better cognitive function during pain is associated with a behavioral strategy.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145332620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neutrophil dynamics in surgical wounds – A novel role of interleukin-7 外科伤口中性粒细胞动力学-白细胞介素-7的新作用

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-09-21 DOI: 10.1016/j.ynpai.2025.100199

Annika Biesold , Philipp Burkard , Ankita Rawat , Laura Cyran , Patrick Meybohm , Heike Rittner , Michael Briese , Nana-Maria Wagner

Postoperative pain and consequently chronic postsurgical pain remain a significant burden among patients. While neutrophilic granulocytes (neutrophils) are known to play a critical role in wound healing, their precise contribution to pain modulation is not fully understood. The neurotrophin nerve growth factor (NGF), released by fibroblasts and immune cells following injury, is an early mediator of pain development. A companion paper demonstrated that NGF administration to axons of cultured sensory neurons in microfluidic chambers induces upregulation of Il7, encoding interleukin-7 (IL-7). However, its role in neutrophil dynamics within surgical wounds remains broadly unclear. In a murine model of laparotomy, we observed that IL-7 was expressed at wound sites and co-localized with sensory nerve endings and infiltrating neutrophils within 24 h post-surgery. Laparotomy triggered neutrophil mobilization from the bone marrow, leading to an influx of both mature and immature neutrophils into the circulation. Flow cytometric analysis further revealed IL-7 receptor (IL-7R) surface expression on neutrophils, with IL-7 stimulation also enhancing the expression of activation and maturation markers on neutrophils in vitro. These findings suggest that NGF-induced IL-7 release from peripheral nerve terminals represents a novel neuroinflammatory mechanism modulating neutrophil dynamics in the surgical wound, potentially impairing wound healing and exacerbating pain. Therefore, targeting IL-7 signalling in peripheral nerves may offer a promising strategy for improving postoperative pain management.

术后疼痛和慢性术后疼痛仍然是患者的重大负担。虽然中性粒细胞（中性粒细胞）已知在伤口愈合中起关键作用，但它们对疼痛调节的确切贡献尚未完全了解。神经营养因子神经生长因子（NGF）由成纤维细胞和免疫细胞在损伤后释放，是疼痛发展的早期中介。另一篇论文表明，在微流控室中，神经生长因子给予培养的感觉神经元轴突可诱导编码白介素-7 （IL-7）的IL-7上调。然而，它在外科伤口中性粒细胞动力学中的作用仍不清楚。在小鼠剖腹手术模型中，我们观察到IL-7在术后24小时内在伤口部位表达，并与感觉神经末梢和浸润中性粒细胞共定位。剖腹手术触发骨髓中性粒细胞动员，导致成熟和未成熟的中性粒细胞涌入循环。流式细胞分析进一步揭示了IL-7受体（IL-7R）表面在中性粒细胞上的表达，IL-7刺激也增强了体外中性粒细胞活化和成熟标志物的表达。这些发现表明，神经生长因子诱导的周围神经末梢IL-7释放代表了一种新的神经炎症机制，可以调节手术伤口中的中性粒细胞动力学，可能损害伤口愈合并加剧疼痛。因此，靶向周围神经中的IL-7信号可能为改善术后疼痛管理提供了一种有希望的策略。

{"title":"Neutrophil dynamics in surgical wounds – A novel role of interleukin-7","authors":"Annika Biesold , Philipp Burkard , Ankita Rawat , Laura Cyran , Patrick Meybohm , Heike Rittner , Michael Briese , Nana-Maria Wagner","doi":"10.1016/j.ynpai.2025.100199","DOIUrl":"10.1016/j.ynpai.2025.100199","url":null,"abstract":"<div><div>Postoperative pain and consequently chronic postsurgical pain remain a significant burden among patients. While neutrophilic granulocytes (neutrophils) are known to play a critical role in wound healing, their precise contribution to pain modulation is not fully understood. The neurotrophin nerve growth factor (NGF), released by fibroblasts and immune cells following injury, is an early mediator of pain development. A companion paper demonstrated that NGF administration to axons of cultured sensory neurons in microfluidic chambers induces upregulation of <em>Il7</em>, encoding interleukin-7 (IL-7). However, its role in neutrophil dynamics within surgical wounds remains broadly unclear. In a murine model of laparotomy, we observed that IL-7 was expressed at wound sites and co-localized with sensory nerve endings and infiltrating neutrophils within 24 h post-surgery. Laparotomy triggered neutrophil mobilization from the bone marrow, leading to an influx of both mature and immature neutrophils into the circulation. Flow cytometric analysis further revealed IL-7 receptor (IL-7R) surface expression on neutrophils, with IL-7 stimulation also enhancing the expression of activation and maturation markers on neutrophils in vitro. These findings suggest that NGF-induced IL-7 release from peripheral nerve terminals represents a novel neuroinflammatory mechanism modulating neutrophil dynamics in the surgical wound, potentially impairing wound healing and exacerbating pain. Therefore, targeting IL-7 signalling in peripheral nerves may offer a promising strategy for improving postoperative pain management.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial commitment to trust and integrity in science: Implications for pain and anesthesiology research 对科学信任和诚信的编辑承诺：对疼痛和麻醉学研究的影响

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 DOI: 10.1016/j.ynpai.2025.100187

Tonya M. Palermo PhD, Didier Bouhassira MD, PhD, Karen D. Davis PhD, FCAHS, FRSC, Hugh C. Hemmings Jr MD, PhD, FRCA, Robert W. Hurley MD, PhD, Joel Katz PhD, Jaideep J. Pandit FRCA, DPhil, DM, MBA, Theodore J. Price PhD, Michael E. Schatman PhD, Stephan K.W. Schwarz MD, PhD, FESAIC, Dennis C. Turk PhD, Marc Van de Velde MD, PhD, EDRA, FESAIC, Matthew D. Wiles MRCP, FCRA, FFICM, Tony L. Yaksh PhD, David Yarnitsky MD

引用次数: 0

Cerebral peak alpha frequency: Associations with chronic pain onset and pain modulation 脑α峰频率：与慢性疼痛发作和疼痛调节的关系

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 Epub Date: 2025-02-28 DOI: 10.1016/j.ynpai.2025.100180

Felicitas A. Huber , Parker A. Kell , Joanna O. Shadlow , Jamie L. Rhudy

Chronic pain is highly prevalent in the U.S. and leads to myriad negative sequalae and suffering. One way to address chronic pain is to identify who is at risk and intervene prior to symptom onset. Research suggests resting peak alpha frequency (PAF), the speed of alpha oscillations at rest, is slower in healthy individuals with greater pain sensitivity and in chronic pain patients. Thus, slower PAF may denote chronic pain vulnerability. Other research has shown that individuals at higher risk of chronic pain exhibit disrupted pain modulation, i.e., less efficient pain inhibition and increased pain facilitation. Currently, the ability of PAF to predict chronic pain and its relation to pain modulation is under-researched. This investigation aimed to address this gap by characterizing associations between PAF, onset of chronic pain, and pain modulation. Using archival data from three independent studies, this investigation assessed whether slower PAF is associated with prospectively-determined chronic pain onset, decreased pain inhibition (i.e., impaired conditioned pain modulation, impaired erotica-induced pain inhibition), and increased pain facilitation (i.e., increased temporal summation of pain, augmented mutilation-induced pain facilitation). Results show that slower PAF was associated with greater facilitation of spinal (i.e., nociceptive flexion reflex) and supraspinal (i.e., N2 potential) nociception in response to unpleasant pictures (i.e., human injury images). This suggests that slower PAF is associated with threat-enhanced spinal and supraspinal nociception and may be relevant for chronic pain conditions with disrupted threat systems. Slower PAF was not associated with any other pain outcome, including prospectively determined chronic pain onset. However, chronic pain onset could only be assessed in one study with a mixed eyes open/eyes closed recording, limiting the significance of this finding.

慢性疼痛在美国非常普遍，并导致无数的负面后遗症和痛苦。解决慢性疼痛的一种方法是确定谁处于危险之中，并在症状发作之前进行干预。研究表明，在疼痛敏感性较高的健康个体和慢性疼痛患者中，静息α峰值频率（PAF），即静息时α振荡的速度较慢。因此，较慢的PAF可能表示慢性疼痛易感性。其他研究表明，慢性疼痛风险较高的个体表现出疼痛调节紊乱，即疼痛抑制效率较低，疼痛促进能力增强。目前，PAF预测慢性疼痛的能力及其与疼痛调节的关系研究尚不充分。本研究旨在通过表征PAF、慢性疼痛发作和疼痛调节之间的关系来解决这一差距。利用三个独立研究的档案数据，本研究评估了PAF减慢是否与预期确定的慢性疼痛发作、疼痛抑制减弱（即条件性疼痛调节受损、性诱发疼痛抑制受损）和疼痛促进增强（即疼痛时间累积增加、残肢诱发疼痛促进增强）相关。结果表明，较慢的PAF与脊柱（即伤害性屈曲反射）和棘上（即N2电位）对不愉快图像（即人体损伤图像）的伤害感觉的更大促进有关。这表明，较慢的PAF与威胁增强的脊髓和椎管上伤害感觉有关，可能与威胁系统中断的慢性疼痛有关。较慢的PAF与任何其他疼痛结果无关，包括前瞻性确定的慢性疼痛发作。然而，慢性疼痛的发作只能在一项研究中通过混合睁眼/闭眼记录进行评估，限制了这一发现的意义。

{"title":"Cerebral peak alpha frequency: Associations with chronic pain onset and pain modulation","authors":"Felicitas A. Huber , Parker A. Kell , Joanna O. Shadlow , Jamie L. Rhudy","doi":"10.1016/j.ynpai.2025.100180","DOIUrl":"10.1016/j.ynpai.2025.100180","url":null,"abstract":"<div><div>Chronic pain is highly prevalent in the U.S. and leads to myriad negative sequalae and suffering. One way to address chronic pain is to identify who is at risk and intervene prior to symptom onset. Research suggests resting peak alpha frequency (PAF), the speed of alpha oscillations at rest, is slower in healthy individuals with greater pain sensitivity and in chronic pain patients. Thus, slower PAF may denote chronic pain vulnerability. Other research has shown that individuals at higher risk of chronic pain exhibit disrupted pain modulation, i.e., less efficient pain inhibition and increased pain facilitation. Currently, the ability of PAF to predict chronic pain and its relation to pain modulation is under-researched. This investigation aimed to address this gap by characterizing associations between PAF, onset of chronic pain, and pain modulation. Using archival data from three independent studies, this investigation assessed whether slower PAF is associated with prospectively-determined chronic pain onset, decreased pain inhibition (i.e., impaired conditioned pain modulation, impaired erotica-induced pain inhibition), and increased pain facilitation (i.e., increased temporal summation of pain, augmented mutilation-induced pain facilitation). Results show that slower PAF was associated with greater facilitation of spinal (i.e., nociceptive flexion reflex) and supraspinal (i.e., N2 potential) nociception in response to unpleasant pictures (i.e., human injury images). This suggests that slower PAF is associated with threat-enhanced spinal and supraspinal nociception and may be relevant for chronic pain conditions with disrupted threat systems. Slower PAF was not associated with any other pain outcome, including prospectively determined chronic pain onset. However, chronic pain onset could only be assessed in one study with a mixed eyes open/eyes closed recording, limiting the significance of this finding.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0