Nerve injury induced microglia activation, which released inflammatory mediators and developed neuropathic pain. Picroside Ⅱ (PⅡ) attenuated neuropathic pain by inhibiting the neuroinflammation of the spinal dorsal horn; however, how it engaged in the cross talk between microglia and neurons remained ambiguous. This study aimed to investigate PⅡ in the modulation of spinal synaptic transmission mechanisms on pain hypersensitivity in neuropathic rats. We investigated the analgesia of PⅡ in mechanical and thermal hyperalgesia using the spinal nerve ligation (SNL)-induced neuropathic pain model and formalin-induced tonic pain model, respectively. RNA sequencing and network pharmacology were employed to screen core targets and signaling pathways. Immunofluorescence staining and qPCR were performed to explore the expression level of microglia and inflammatory mediator mRNA. The whole-cell patch-clamp recordings were utilized to record miniature excitatory postsynaptic currents in excitatory synaptic transmission. Our results demonstrated that the analgesic of PⅡ was significant in both pain models, and the underlying mechanism may involve inflammatory signaling pathways. PⅡ reversed the SNL-induced overexpression of microglia and inflammatory factors. Moreover, PⅡ dose dependently inhibited excessive glutamate transmission. Thus, this study suggested that PⅡ attenuated neuropathic pain by inhibiting excitatory glutamate transmission of spinal synapses, induced by an inflammatory response on microglia.
Keywords: inflammation; neuropathic pain; picroside Ⅱ; synaptic transmission.