Wang Shumin, Ren Shuting, Lv Siting, Liu Yuankun, Xing Keke, Zhang Ting, Jin Xiaohang, Shi Juan
Department of Human Anatomy, Histology and Embryology & K. K. Leung Brain Research Centre, Preclinical School of Medicine, The Fourth Military Medical University, Xi'an, China.
Medical School of Yan'an University, Yan'an, China.
J Neuroendocrinol. 2025 Aug;37(8):e70045. doi: 10.1111/jne.70045. Epub 2025 May 12.
Neuropathic pain is the debilitating chronic pain frequently comorbid with anxiety and depression. The mechanism and treatment strategy of neuropathic pain are to be elucidated. Oxytocin (OXT)-containing neurons (simplified as OXT neurons) in the hypothalamic paraventricular nucleus (PVN) have been highlighted recently in the field of pain regulation and social function. But so far, the adaptive change and endogenous function of the neurons in neuropathic pain remain unclear. By immunofluorescent staining, we investigated the changes in FOSB expression in OXT neurons in the PVN with the development of neuropathic pain induced by spared nerve injury (SNI). The effect of neuronal activation on pain, as well as comorbid anxiety and depression, was subsequently assessed by chemogenetic manipulation. FOSB expression in the OXT neurons was significantly increased at 1 day and then gradually decreased at 7, 28, and 49 days after SNI. Activation of OXT neurons in the PVN by the OXT promoter-directed hM3Dq virus or by the Cre-loxP system in OXT-Cre mice significantly improved the mechanical pain, cold pain, and depressive-like behaviors in male and female mice, but exerted weak anxiolytic effects in female mice. These results demonstrate the altered activational status and the analgesic/antidepressant role of the OXT neurons in the PVN, thus providing a cellular-based strategy for the comprehensive treatment of neuropathic pain.
神经性疼痛是一种使人衰弱的慢性疼痛，常与焦虑和抑郁并存。神经性疼痛的机制和治疗策略有待阐明。下丘脑室旁核（PVN）中含催产素（OXT）的神经元（简称为OXT神经元）最近在疼痛调节和社会功能领域受到关注。但迄今为止，神经性疼痛中这些神经元的适应性变化和内源性功能仍不清楚。通过免疫荧光染色，我们研究了在 spared nerve injury（SNI）诱导的神经性疼痛发展过程中，PVN中OXT神经元FOSB表达的变化。随后通过化学遗传学操作评估神经元激活对疼痛以及共病焦虑和抑郁的影响。SNI后1天，OXT神经元中的FOSB表达显著增加，然后在7天、28天和49天时逐渐下降。通过OXT启动子导向的hM3Dq病毒或在OXT-Cre小鼠中通过Cre-loxP系统激活PVN中的OXT神经元，可显著改善雄性和雌性小鼠的机械性疼痛、冷痛和抑郁样行为，但对雌性小鼠的抗焦虑作用较弱。这些结果证明了PVN中OXT神经元激活状态的改变及其镇痛/抗抑郁作用，从而为神经性疼痛的综合治疗提供了一种基于细胞的策略。
