延髓腹侧髓质中的星形胶质细胞介导电针中的电针的镇痛作用，在化学疗法诱导的周围神经性疼痛
Astrocytes in the rostral ventromedial medulla mediate the analgesic effect of electroacupuncture in a rodent model of chemotherapy-induced peripheral neuropathic pain
影响因子:5.50000
分区:医学1区 Top / 麻醉学2区 临床神经病学2区 神经科学2区
发表日期:2025 Apr 01
作者:
Xuejiao Chen, Wenli Mi, Tianchi Gao, Fengfei Ding, Wei Wang
摘要
化学疗法引起的周围神经性疼痛加剧了癌症幸存者的生活负担。在先前的研究中，电针仪（EA）对神经性疼痛表现出了有希望的镇痛作用。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神经性疼痛以及EA的止痛作用的过程中，星形胶质细胞在腹侧髓质髓质（RVM）中的功能作用。我们发现，紫杉醇会在RVM和脊髓中诱导机械性异常性钙，星形钙信号传导和神经元激活，可以通过EA治疗抑制。电针有效地缓解了紫杉醇诱导的机械性异常性疾病，并且通过RVM中星形胶质细胞的化学遗传激活减轻了效果。此外，通过使用IP 3 R2敲除（IP 3 R2 KO）小鼠或将AAV介导的HPMCA2 W/B的显微注射抑制星形钙钙活性，以减少星形胶质细胞中星形胶质细胞中非IP 3 R2依赖性Ca 2+信号的降低对神经性疼痛表现出对神经病变疼痛的效果，从而对效应产生了仿制。当前的研究揭示了RVM星形胶质细胞在介导EA对化学疗法诱导的周围神经性疼痛的镇痛作用中的关键作用。
Abstract
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 IP 3 R2 knockout (IP 3 R2 KO) mice or microinjection of AAV-mediated hPMCA2 w/b into the RVM to reduce non-IP 3 R2-dependent Ca 2+ 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.