• 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, and Xinzhong Chen.
• Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
• Pain. 2024 Aug 6.

AbstractMenopausal 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 (DRNGABA) neurons. Moreover, activation of the DRNGABA neurons projecting to the lateral parabrachial nucleus was critical for alleviating hyperalgesia in OVX mice. These findings show the essential role of DRNGABA 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.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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