Neurobiology of Pain最新文献_第2页

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 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。

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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 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。

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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 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 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。

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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 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。

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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

Unveiling the peripheral nerve hallmarks of chemotherapy-induced neuropathy: insights from paclitaxel treatment in a murine model 揭示化疗引起的神经病变的周围神经特征：来自紫杉醇治疗小鼠模型的见解

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 DOI: 10.1016/j.ynpai.2025.100200

Maria Maiarù , Andrea Petrini , Federica De Angelis , Francesca Nazio , Sara Marinelli

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating side effect of anticancer drugs like paclitaxel, significantly reducing the quality of life for cancer patients. Paclitaxel-induced peripheral neuropathy (PIPN) is primarily characterized by sensory disturbances such as mechanical allodynia and thermal hyperalgesia. Despite its prevalence, the mechanisms driving PIPN are not fully understood, and current treatment options remain limited. This study explores the impact of varying doses of paclitaxel on neuropathic pain, nerve structural changes, and metabolic alterations in a mouse model. Behavioural assessments demonstrated that paclitaxel induced dose-dependent mechanical allodynia and thermal hyperalgesia, with prolonged symptoms at higher doses. Furthermore, sciatic nerve dysfunction was observed, while metabolic tests revealed significant disruptions in glucose and triglyceride levels, suggesting a link between metabolic imbalances and neuropathy. Histological and molecular analyses identified increased TRPV1 and CGRP expression in skin nerve fibers, accompanied by Schwann cell dysfunction, characterized by myelin disorganization, decreased levels of myelin proteins (P0, MBP), and elevated LC3 levels, pointing to autophagy involvement. Moreover, infiltration of macrophages and mast cells into sciatic nerves indicated an innate immune response. These results emphasize the complex nature of PIPN, which involves sensory nerve sensitization, Schwann cell damage, and metabolic dysregulation. Elucidating these pathways could inform the development of more effective therapies aimed at preventing or alleviating the impact of CIPN.

化疗诱导的周围神经病变（CIPN）是紫杉醇等抗癌药物常见的衰弱性副作用，显著降低癌症患者的生活质量。紫杉醇诱导的周围神经病变（PIPN）主要以感觉障碍为特征，如机械性异常性痛和热痛觉过敏。尽管PIPN很普遍，但其发病机制尚不完全清楚，目前的治疗方案仍然有限。本研究在小鼠模型中探讨了不同剂量紫杉醇对神经性疼痛、神经结构改变和代谢改变的影响。行为评估表明，紫杉醇诱导剂量依赖性机械异常性痛和热痛觉过敏，高剂量时症状延长。此外，观察到坐骨神经功能障碍，而代谢测试显示葡萄糖和甘油三酯水平明显中断，表明代谢失衡与神经病变之间存在联系。组织学和分子分析发现，皮肤神经纤维中TRPV1和CGRP表达增加，伴有雪旺细胞功能障碍，其特征是髓磷脂紊乱，髓磷脂蛋白（P0， MBP）水平降低，LC3水平升高，表明自噬参与。此外，巨噬细胞和肥大细胞浸润坐骨神经表明先天免疫反应。这些结果强调了PIPN的复杂性，包括感觉神经敏化、雪旺细胞损伤和代谢失调。阐明这些途径可以为开发更有效的治疗方法提供信息，旨在预防或减轻CIPN的影响。

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引用次数: 0

Left nucleus accumbens volume is associated with poor sleep in hip osteoarthritis 左伏隔核体积与髋关节骨关节炎患者睡眠质量差有关

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 DOI: 10.1016/j.ynpai.2025.100203

Natalia Egorova-Brumley , Luiza Bonfim Pacheco , Gabby Knox , Leila Nategh , Fiona Dobson , Michelle Hall

Objective

Reduction in the volume of the nucleus accumbens (NAc) has emerged as a promising signature of chronic pain transition, including in osteoarthritis (OA). Yet, less is known about the factors that could influence these changes in the mesolimbic system. Given that poor sleep is common in OA, and recent studies of sleep disturbance on pain perception in animals and healthy populations have specifically implicated the NAc, we hypothesised that the left NAc volume in hip OA would be associated with sleep quality and quantity. Furthermore, we explored how sex interacts with this relationship.

Methods

Cross-sectional study in participants with hip OA (n = 34; aged 60+/-12 years, 67 % females) who reported moderate pain were recruited.

Results

A one-sample t-test showed that the left NAc volumes were significantly lower than normative values (t = -2.7368, df = 33, p-value = 0.009). In a model (F(4, 29) = 6.642, p < 0.001, R2 = 0.4781) including the total intracranial volume (TIV), sex and age, the left NAc volume was significantly predicted by sleep quality (t = -3.416, p = 0.002) assessed with Pittsburgh Sleep Quality Index (PSQI). Sleep efficiency (t = 2.362, p = 0.025) but not hours spent in bed (p > 0.05) was also a significant predictor. With models exploring sleep*sex interactions, only sleep efficiency demonstrated an interaction, suggesting that the left NAc volume is lower in females with worse sleep efficiency (t = -2.086, p = 0.046, albeit not significant when corrected for multiple comparisons, pFDR = 0.138.)

Conclusions

Our results suggest that the reduction of the NAc volumes as a candidate biomarker of pain might be influenced by sleep. This exploratory finding in a chronic hip OA population is consistent with the results previously only reported in animal and experimental pain/sleep studies in healthy participants.

Significance

The left NAc as a candidate biomarker of chronic pain is sensitive to the effects of sleep quality, especially in females with OA.

伏隔核（NAc）体积的减少已成为慢性疼痛过渡的一个有希望的标志，包括骨关节炎（OA）。然而，人们对影响中边缘系统这些变化的因素知之甚少。鉴于睡眠质量差在OA患者中很常见，并且最近在动物和健康人群中关于睡眠障碍对疼痛感知的研究特别涉及了NAc，我们假设髋OA患者左侧NAc体积与睡眠质量和睡眠量有关。此外，我们还探讨了性如何与这种关系相互作用。方法对报告中度疼痛的髋关节OA患者（34例，年龄60+/-12岁，67%为女性）进行横断面研究。结果单样本t检验结果显示，左NAc体积显著低于正常值（t = -2.7368, df = 33， p值= 0.009）。在包含颅内总容积（TIV）、性别和年龄的模型（F(4,29) = 6.642, p < 0.001, R2 = 0.4781）中，以匹兹堡睡眠质量指数（PSQI）评估的睡眠质量（t = -3.416, p = 0.002）显著预测左NAc容积。睡眠效率（t = 2.362, p = 0.025），而非卧床时间（p > 0.05）也是显著的预测因子。在探索睡眠与性别相互作用的模型中，只有睡眠效率显示出了相互作用，这表明睡眠效率较差的女性左NAc体积更低（t = -2.086, p = 0.046，尽管在进行多重比较校正后并不显著，pFDR = 0.138）。结论NAc体积的减少作为疼痛的候选生物标志物可能受到睡眠的影响。这一在慢性髋关节炎人群中的探索性发现与之前仅在健康参与者的动物和实验性疼痛/睡眠研究中报道的结果一致。左侧NAc作为慢性疼痛的候选生物标志物对睡眠质量的影响很敏感，尤其是在OA女性患者中。

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引用次数: 0

Circulating microRNAs differentiate nociceptive and nociplastic pain: An exploratory study 循环microRNAs区分伤害性和伤害性疼痛：一项探索性研究

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 DOI: 10.1016/j.ynpai.2025.100191

Hiroyuki Nishie , Hideki Nakatsuka , Kazunori Iwasa , Yuka Sakuta , Yuichiro Toda , Shigeru Mitani , Takeshi Nagasaka

Background

Nociceptive and nociplastic pain arise from distinct biological mechanisms, yet their differentiation remains clinically challenging. Circulating microRNAs (miRNAs) are promising candidates for objective, mechanism-based pain classification.

Objective

To explore whether specific circulating miRNAs can differentiate nociceptive pain in patients with hip osteoarthritis (HO) from nociplastic pain in patients with chronic primary pain (CPP), and to assess their relationship with clinical and psychological outcomes.

Methods

In this exploratory, single-center study, plasma samples were collected from patients with HO (n = 13), CPP (n = 11), and healthy controls (n = 7). Microarray screening identified candidate miRNAs, which were validated via real-time PCR. Pain intensity (NRS), disability (PDAS), quality of life (EQ-5D), and psychological factors (PCS, PSEQ, TSK-11, PHQ-9) were assessed. Classification accuracy was evaluated using decision tree modeling and ROC analysis.

Results

Let-7a, miR-26a, and miR-16 showed distinct expression profiles and contributed to a predictive model with strong performance (R² = 0.677; AUC > 0.94). Let-7a expression was associated with structural joint changes in HO but not subjective pain ratings. MiR-26a correlated with cognitive-affective pain traits in CPP, and miR-16 decreased following CBT, suggesting a role in treatment-related neuroplasticity. MiR-126 and miR-146a were linked to reductions in pain intensity post-surgery in the HO group. QOL improved in HO, while psychological factors remained prominent in CPP.

Conclusions

This pilot study suggests that circulating miRNAs may aid in differentiating nociceptive and nociplastic pain mechanisms and tracking treatment effects. While preliminary, these findings support the potential utility of miRNA-based biomarkers in precision pain diagnostics and personalized management strategies.

背景：伤害性疼痛和伤害性疼痛产生于不同的生物学机制，但它们的区分在临床上仍然具有挑战性。循环microRNAs （miRNAs）是基于客观机制的疼痛分类的有希望的候选者。目的探讨特异性循环mirna是否能够区分髋关节骨关节炎（HO）患者的伤害性疼痛和慢性原发性疼痛（CPP）患者的伤害性疼痛，并评估它们与临床和心理结局的关系。方法在本探索性单中心研究中，收集HO患者（n = 13）、CPP患者（n = 11）和健康对照（n = 7）的血浆样本。微阵列筛选确定候选mirna，并通过实时PCR验证。评估疼痛强度（NRS）、残疾程度（PDAS）、生活质量（EQ-5D）和心理因素（PCS、PSEQ、TSK-11、PHQ-9）。采用决策树模型和ROC分析评估分类精度。结果slet -7a、miR-26a和miR-16表现出不同的表达谱，对预测模型有很强的作用(R2 = 0.677；AUC祝辞0.94)。Let-7a表达与HO的关节结构变化有关，但与主观疼痛评分无关。MiR-26a与CPP的认知-情感性疼痛特征相关，并且miR-16在CBT后下降，提示在治疗相关的神经可塑性中起作用。MiR-126和miR-146a与HO组术后疼痛强度的降低有关。HO患者的生活质量改善，而CPP患者的心理因素仍然突出。结论本初步研究表明，循环mirna可能有助于区分伤害性和伤害性疼痛机制，并追踪治疗效果。虽然是初步的，但这些发现支持了基于mirna的生物标志物在精确疼痛诊断和个性化管理策略中的潜在效用。

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引用次数: 0

FL/FLT3 signaling enhances mechanical pain hypersensitivity through Interleukin-1 beta (IL-1β) in male mice FL/FLT3信号通过白细胞介素-1β (IL-1β)增强雄性小鼠的机械性疼痛超敏反应

Q2 Medicine

Neurobiology of Pain

Pub Date : 2025-07-01 DOI: 10.1016/j.ynpai.2025.100202

Corinne Sonrier , Chamroen Sar , Ivo Melo , Lucie Dioufoulet , Gabriel V. Lucena-Silva , Sylvie Mallié , Juliette Bertin , Jean-Philippe Leyris , Fabrice Ango , Thiago M. Cunha , Hamid Moha ou Maati , Jean Valmier , Cyril Rivat , Ilana Méchaly

Fms-like tyrosine kinase 3 (FLT3) plays a critical role in chronic pain through its ligand FL, a cytokine that triggers mechanical pain hypersensitivity. However, the underlying molecular mechanisms remain unclear. Here, we investigate the potential interplay between FL and IL-1β a key cytokine in DRG neurons sensitization and mechanical hyperalgesia through both in vitro and in vivo approaches. ELISA assays reveal that intrathecal FL administration significantly increases IL-1β protein levels in both the DRG and dorsal spinal cord of mice, by four hours post-injection. Using video microscopy and [Ca²⁺] ₁ fluorescence imaging in primary DRG neuron cultures, we demonstrate that FL potentiation of TRPV1 receptor responses to capsaicin is partially mediated by IL-1β signalling, as evidenced by a significant reduction in this potentiation in the presence of the IL-1 receptor antagonist, IL-1Ra. Furthermore, FLT3-driven acute mechanical pain hypersensitivity in vivo is reduced both by prior administration of IL-1Ra and in IL-1 receptor knockout mice. Importantly, IL-1β-induced mechanical pain hypersensitivity remains independent of FLT3 signalling as shown in Flt3 knockout mice. Collectively our findings expand the understanding of neuro-immune interactions by demonstrating a potential functional link between FL/FLT3 and IL-1β/IL-1R signalling in nociceptive processing.

fms样酪氨酸激酶3 （FLT3）通过其配体FL在慢性疼痛中起关键作用，FL是一种触发机械性疼痛超敏反应的细胞因子。然而，潜在的分子机制尚不清楚。在这里，我们通过体外和体内两种方法研究了FL和IL-1β之间的潜在相互作用，IL-1β是DRG神经元致敏和机械性痛觉过敏的关键细胞因子。ELISA检测显示，鞘内给药4小时后，小鼠DRG和脊髓背段IL-1β蛋白水平均显著升高。使用视频显微镜和[Ca2+] 1荧光成像在原代DRG神经元培养中，我们证明了TRPV1受体对辣椒素反应的FL增强部分是由IL-1β信号介导的，IL-1受体拮抗剂IL-1Ra的存在显著降低了这种增强。此外，预先给药IL-1Ra和IL-1受体敲除小鼠可减少体内flt3驱动的急性机械性疼痛超敏反应。重要的是，在FLT3敲除小鼠中显示，il -1β诱导的机械性疼痛超敏反应仍然独立于FLT3信号传导。总的来说，我们的研究结果通过证明FL/FLT3和IL-1β/IL-1R信号在伤害性加工中的潜在功能联系，扩大了对神经免疫相互作用的理解。

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引用次数: 0