Astrocytes in the rostral ventromedial medulla mediate the analgesic effect of electroacupuncture in a rodent model of chemotherapy-induced peripheral neuropathic pain.

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 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.