Activation of GABAergic neurons in the dorsal raphe nucleus alleviates hyperalgesia induced by ovarian hormone withdrawal.

IF 5.9 1区医学 Q1 ANESTHESIOLOGY PAIN® Pub Date : 2025-04-01 Epub Date: 2024-08-06 DOI:10.1097/j.pain.0000000000003362

Hui Wu, Linghua Xie, Qing Chen, Fang Xu, Ange Dai, Xiaolin Ma, Shulan Xie, Hua Li, Fangfang Zhu, Cuicui Jiao, Lihong Sun, Qi Xu, Yudong Zhou, Yi Shen, Xinzhong Chen

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Abstract

Abstract: Menopausal and postmenopausal women, characterized by a significant reduction in ovarian hormones, have a high prevalence of chronic pain with great pain intensity. However, the underlying mechanism of hyperalgesia induced by ovarian hormone withdrawal remains poorly understood. Here, we report that decreases in the activity and excitability of GABAergic neurons in the dorsal raphe nucleus (DRN) are associated with hyperalgesia induced by ovariectomy in mice. Supplementation with 17β-estradiol, but not progesterone, is sufficient to increase the mechanical pain threshold in ovariectomized (OVX) mice and the excitability of DRN GABAergic (DRN GABA ) neurons. Moreover, activation of the DRN GABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRN GABA neurons and their modulation by estrogen in regulating hyperalgesia induced by ovarian hormone withdrawal, providing therapeutic basis for the treatment of chronic pain in physiological or surgical menopausal women.

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激活背侧剑突核的 GABA 能神经元可减轻卵巢激素戒断引起的痛觉减退。

摘要：绝经期和绝经后妇女的特点是卵巢激素明显减少，她们的慢性疼痛发病率高，疼痛强度大。然而，人们对卵巢激素撤退诱发痛觉减退的内在机制仍然知之甚少。在这里，我们报告了背侧剑突核（DRN）GABA能神经元活性和兴奋性的降低与卵巢切除诱导的小鼠痛觉减退有关。补充 17β-雌二醇（而非孕酮）足以提高卵巢切除（OVX）小鼠的机械痛阈值和 DRN GABA 能（DRNGABA）神经元的兴奋性。此外，激活投射到外侧脐旁核的 DRNGABA 神经元对于缓解卵巢切除小鼠的痛觉减退至关重要。这些研究结果表明，DRNGABA神经元及其受雌激素的调节作用在调节由卵巢激素撤退引起的痛觉减退中起着至关重要的作用，为治疗生理性或手术性绝经妇女的慢性疼痛提供了治疗依据。

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

PAIN® 医学-临床神经学

CiteScore

12.50

自引率

8.10%

发文量

242

审稿时长

9 months

期刊介绍： PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.