Paeoniflorin relieves LPS-induced inflammatory pain in mice by inhibiting NLRP3 inflammasome activation via transient receptor potential vanilloid 1.

Abstract:

: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 Ca2+ levels, 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 Ca2+ concentration, 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 Ca2+ levels, 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.

journal_name

J Leukoc Biol

authors

Yin N,Gao Q,Tao W,Chen J,Bi J,Ding F,Wang Z

doi

10.1002/JLB.3MA0220-355R

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

229-241

issue

1

eissn

0741-5400

issn

1938-3673

journal_volume

108

pub_type

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