Effects and Mechanisms of Paeoniflorin in Relieving Neuropathic Pain: Network Pharmacological Analysis and Experimental Validation

Neuropathic pain (NP) is a prevalent condition that can lead to a variety of complications, significantly impacting patients' quality of life. Previous studies have confirmed that paeoniflorin (PF) demonstrates both therapeutic pain relief and neuroprotective effects. However, its therapeutic efficacy in managing NP remains to be thoroughly investigated. We conducted a systematic study to explore the underlying mechanisms of PF in the treatment of NP through combining network pharmacological analysis with experimental validation. Our studies revealed that PF alleviates NP through a multifaceted approach, mainly involving protein kinase C (PKC), serotonin receptors, calcium signaling pathways, inflammatory mediator regulation of transient receptor potential (TRP) channels, and G-protein coupled receptor signaling pathways. Additionally, our animal experiments indicated that PF reduces pain-related behavior on spinal nerve ligation-induced NP in rats by modulating the PKCε-TRPV1 pathway. PF was found to inhibit the expression of inflammatory factors such as interleukin 6 and tumor necrosis factor α, as well as the activation of microglia, thereby alleviating NP. These findings suggest a potential therapeutic role for PF in the treatment of NP, providing a valuable reference for clinical applications.