丘脑前腹外侧核星形胶质细胞介导电针治疗在啮齿动物化疗引起的周围神经病理性疼痛模型中的镇痛作用
Astrocytes in the rostral ventromedial medulla mediate the analgesic effect of electroacupuncture in a rodent model of chemotherapy-induced peripheral neuropathic pain
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影响因子:5.5
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
DOI:
10.1097/j.pain.0000000000003433
摘要
化疗引起的周围神经病理性疼痛加重了癌症幸存者的生活负担。电针（EA）在先前的研究中显示出对神经病理性疼痛具有良好的镇痛效果。我们探讨了电针在紫杉醇诱导的神经病理性疼痛小鼠模型中的有效性，并进一步研究了丘脑前腹外侧核（RVM）中星形胶质细胞在神经病理性疼痛过程及电针镇痛作用中的功能作用。研究发现，紫杉醇诱导机械性异位痛、星形胶质细胞钙信号和神经元激活，均可被电针治疗所抑制。电针有效缓解紫杉醇引起的机械性异位痛，其效应在通过化学遗传激活RVM中的星形胶质细胞后减弱。此外，使用IP3 R2敲除（IP3 R2 KO）小鼠或微注射AAV介导的hPMCA2 w/b进入RVM，以减少星形胶质细胞中非IP3 R2依赖的Ca2+信号，表现出神经病理性疼痛的镇痛作用，类似于电针的效果。本研究揭示了RVM星形胶质细胞在调节电针对化疗引起的周围神经病理性疼痛的镇痛作用中的关键角色。
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.