国家补充和综合健康中心Alexander T. Chesler研究组取得一项新突破。他们报道了热感觉和炎症性疼痛的分布式编码逻辑。2025年4月23日，国际知名学术期刊《自然》发表了这一成果。

通过结合功能成像和多路原位杂交，研究小组确定了热刺激和机械刺激是如何在神经元类别中编码的，以及炎症如何将这种表征转化为热过敏、机械异常性疼痛和持续疼痛。他们的数据显示，支配脸颊的三叉神经对轻触和热的反应完全分离。相比之下，高温和低温机械刺激广泛激活伤害感受器类别，包括被提议触发特定感知和行为的细胞类型。注射炎症介质前列腺素E2可使某些类型的伤害感受器具有持久的活性和热致敏性，为持续的炎症性疼痛和热超敏性提供细胞基础。研究团队发现辣椒素受体TRPV1 (ref.7)在热敏作用中起核心作用，但在自发伤害感受器活动中不起作用。出乎意料的是，对机械刺激的反应受到炎症的影响最小，这表明触觉异常性痛是由与触觉同时发生的伤害感受器持续放电引起的。事实上，该课题组人员已经证明，伤害感受器的活动是必要和充分的炎症性触觉异常性痛。总之，这些发现完善了细胞和分子水平上的感觉编码和区分模型，证明了触摸和温度在转录组学上不同的感觉细胞群体中广泛但差异地编码，并提供了关于炎症如何重塑细胞水平反应以触发疼痛的不同方面的见解。

据了解，体感神经元编码有关触觉和温度的详细信息，是疼痛的外围驱动因素。

附：英文原文

Title: A distributed coding logic for thermosensation and inflammatory pain

Author: Ghitani, Nima, von Buchholtz, Lars J., MacDonald, Donald Iain, Falgairolle, Melanie, Nguyen, Minh Q., Licholai, Julia A., Ryba, Nicholas J. P., Chesler, Alexander T.

Issue&Volume: 2025-04-23

Abstract: Somatosensory neurons encode detailed information about touch and temperature and are the peripheral drivers of pain1,2. Here by combining functional imaging with multiplexed in situ hybridization3, we determined how heat and mechanical stimuli are encoded across neuronal classes and how inflammation transforms this representation to induce heat hypersensitivity, mechanical allodynia and continuing pain. Our data revealed that trigeminal neurons innervating the cheek exhibited complete segregation of responses to gentle touch and heat. By contrast, heat and noxious mechanical stimuli broadly activated nociceptor classes, including cell types proposed to trigger select percepts and behaviours4,5,6. Injection of the inflammatory mediator prostaglandin E2 caused long-lasting activity and thermal sensitization in select classes of nociceptors, providing a cellular basis for continuing inflammatory pain and heat hypersensitivity. We showed that the capsaicin receptor TRPV1 (ref.7) has a central role in heat sensitization but not in spontaneous nociceptor activity. Unexpectedly, the responses to mechanical stimuli were minimally affected by inflammation, suggesting that tactile allodynia results from the continuing firing of nociceptors coincident with touch. Indeed, we have demonstrated that nociceptor activity is both necessary and sufficient for inflammatory tactile allodynia. Together, these findings refine models of sensory coding and discrimination at the cellular and molecular levels, demonstrate that touch and temperature are broadly but differentially encoded across transcriptomically distinct populations of sensory cells and provide insight into how cellular-level responses are reshaped by inflammation to trigger diverse aspects of pain.

DOI: 10.1038/s41586-025-08875-6

Source: https://www.nature.com/articles/s41586-025-08875-6