Chemotherapy-induced peripheral neuropathic pain aggravates cancer survivors' life burden. Electroacupuncture (EA) has exhibited promising analgesic effects on neuropathic pain in previous studies. We investigated whether EA was effective in a paclitaxel-induced neuropathic pain mouse model. We further explored the functional role of astrocytes in the rostral ventromedial medulla (RVM), a well-established pain modulation center, in the process of neuropathic pain as well as the analgesic effect of EA. We found that paclitaxel induced mechanical allodynia, astrocytic calcium signaling, and neuronal activation in the RVM and spinal cord, which could be suppressed by EA treatment. Electroacupuncture effectively alleviated paclitaxel-induced mechanical allodynia, and the effect was attenuated by the chemogenetic activation of astrocytes in the RVM. In addition, inhibiting astrocytic calcium activity by using either IP3R2 knockout (IP3R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non-IP3R2-dependent Ca2+ signaling in astrocytes exhibited an analgesic effect on neuropathic pain, which mimicked the EA effect. The current study revealed the pivotal role of the RVM astrocytes in mediating the analgesic effects of EA on chemotherapy-induced peripheral neuropathic pain.

中文翻译：

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喙腹内侧延髓中的星形胶质细胞在化疗诱导的周围神经性疼痛的啮齿动物模型中介导电针的镇痛作用。


化疗引起的周围神经性疼痛加重了癌症幸存者的生活负担。电针 （EA） 在以前的研究中对神经性疼痛显示出有希望的镇痛作用。我们研究了 EA 在紫杉醇诱导的神经性疼痛小鼠模型中是否有效。我们进一步探讨了星形胶质细胞在脑腹内侧延髓 （RVM） 中的功能作用，这是一个成熟的疼痛调节中心，在神经性疼痛过程中以及 EA 的镇痛作用。我们发现紫杉醇诱导了 RVM 和脊髓中的机械异常性疼痛、星形胶质细胞钙信号传导和神经元激活，这可以通过 EA 治疗来抑制。电针有效缓解紫杉醇诱导的机械性异常性疼痛，并且 RVM 中星形胶质细胞的化学发生激活减弱了这种影响。此外，通过使用 IP3R2 敲除 （IP3R2 KO） 小鼠或将 AAV 介导的 hPMCA2 w/b 显微注射到 RVM 中以减少星形胶质细胞中非 IP3R2 依赖性 Ca2 + 信号传导来抑制星形胶质细胞钙活性，对神经性疼痛表现出镇痛作用，这模拟了 EA 效应。目前的研究揭示了 RVM 星形胶质细胞在介导 EA 对化疗引起的周围神经性疼痛的镇痛作用中的关键作用。