Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1.
J Leukoc Biol. 2020 Feb 21. Epub 2020 Feb 21. PMID: 32083340
LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analgesic effect of PF on an inflammatory pain mouse model and explore the underlying mechanisms. LPS-induced inflammatory pain model was established in C57BL/6J mice after PF treatment. Then, thermal hyperalgesia, neutrophil infiltration, inflammatory cytokine production, intracellular Calevels, PKC activity, transient receptor potential vanilloid 1 (TRPV-1) expression, NF-κB transcription, and NLPR3 inflammasome activation were assessed by thermal withdrawal latency, histopathology, ELISA, intracellular Caconcentration, immunohistochemistry, and Western blot, separately. PF significantly relieved inflammatory pain and paw edema in mice with LPS-induced inflammatory pain. Additionally, PF inhibited neutrophil infiltration, inflammatory cytokine production (IL-1β, TNF-α, and IL-6), intracellular Calevels, and PKC activity as well as suppressed TRPV-1 expression, NF-κB transcription, and NLPR3 inflammasome activation in the footpad tissue samples. Importantly, capsaicin (TRPV-1 agonists) obviously reversed the pain-relieving effect of PF, suggesting the involvement of TRPV-1 in the analgesic activity of PF. Our results indicated PF ameliorated LPS-induced inflammation and pain in mice by inhibiting TRPV-1-mediated NLRP3 inflammasome activation. These findings suggest that PF can be as a potential pharmacological agent for inflammatory pain and thus deserves more attention and further investigation.