Picroside Ⅱ attenuates neuropathic pain by regulating inflammation and spinal excitatory synaptic transmission

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 (mEPSCs) 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.PMID:37976472 | DOI:10.1139/cjpp-2023-0171
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research