A parabrachial hub for need-state control of enduring pain.

IF 48.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Pub Date : 2025-10-08 DOI:10.1038/s41586-025-09602-x

Nitsan Goldstein,Amadeus Maes,Heather N Allen,Tyler S Nelson,Kayla A Kruger,Morgan Kindel,Albert T M Yeung,Nicholas K Smith,Jamie R E Carty,Lavinia Boccia,Niklas Blank,Emily Lo,Rachael E Villari,Ella Cho,Erin L Marble,Michelle Awh,Yasmina Dumiaty,Melissa J Chee,Rajesh Khanna,Christoph A Thaiss,Bradley K Taylor,Ann Kennedy,J Nicholas Betley

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Abstract

Long-term sustained pain following acute physical injury is a prominent feature of chronic pain conditions1. Populations of neurons that rapidly respond to noxious stimuli or tissue damage have been identified in the spinal cord and several nuclei in the brain2-4. Understanding the central mechanisms that signal ongoing sustained pain, including after tissue healing, remains a challenge5. Here we use spatial transcriptomics, neural manipulations, activity recordings and computational modelling to demonstrate that activity in an ensemble of anatomically and molecularly diverse parabrachial neurons that express the neuropeptide Y (NPY) receptor Y1 (Y1R neurons) is increased following injury and predicts functional coping behaviour. Hunger, thirst or predator cues suppressed sustained pain, regardless of the injury type, by inhibiting parabrachial Y1R neurons via the release of NPY. Together, our results demonstrate an endogenous analgesic hub at pain-responsive parabrachial Y1R neurons.

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一个控制疼痛需要状态的臂旁中枢。

急性身体损伤后的长期持续疼痛是慢性疼痛的一个显著特征。对有害刺激或组织损伤迅速作出反应的神经元群已经在脊髓和大脑的几个核中被发现2-4。了解持续疼痛（包括组织愈合后）信号的中心机制仍然是一个挑战。在这里，我们使用空间转录组学、神经操作、活动记录和计算模型来证明，在解剖学和分子上多样化的臂旁神经元中，表达神经肽Y （NPY）受体Y1 （Y1R神经元）的活动在损伤后增加，并预测功能性应对行为。无论损伤类型如何，饥饿、口渴或捕食者线索都能通过释放NPY抑制臂旁Y1R神经元，从而抑制持续疼痛。总之，我们的研究结果表明，在疼痛反应的臂旁Y1R神经元中存在内源性镇痛中枢。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature 综合性期刊-综合性期刊

CiteScore

90.00

自引率

1.20%

发文量

3652

审稿时长

3 months

期刊介绍： Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.