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 (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.

中文翻译：

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中缝背核中 GABA 能神经元的激活可减轻卵巢激素撤退引起的痛觉过敏。


更年期和绝经后妇女的特点是卵巢激素显着减少，慢性疼痛的患病率很高，且疼痛强度很大。然而，卵巢激素撤退引起的痛觉过敏的潜在机制仍知之甚少。在这里，我们报告说，中缝背核（DRN）中 GABA 能神经元的活性和兴奋性降低与小鼠卵巢切除引起的痛觉过敏有关。补充 17β-雌二醇（而非黄体酮）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，激活投射到臂旁核外侧核的 DRNGABA 神经元对于减轻 OVX 小鼠的痛觉过敏至关重要。这些发现表明了DRNGABA神经元及其受雌激素的调节在调节卵巢激素撤退引起的痛觉过敏中的重要作用，为治疗生理或手术绝经期妇女的慢性疼痛提供了治疗基础。