Eucalyptol Alleviates Inflammation and Pain Responses in a Mouse Model of Gout Arthritis.

Gout arthritis, which is provoked by monosodium urate (MSU) crystal accumulation in the joint and periarticular tissues, induces severe pain and affects life quality of the patients. Eucalyptol (1, 8-cineol), the principal component in the essential oils of eucalyptus leaves, has been known to possess anti-inflammatory and analgesic properties. We aimed to examine the therapeutic effects of eucalyptol on gout arthritis and related mechanisms.A mouse model of gout arthritis was established via MSU injection into the ankle joint. Ankle edema, mechanical allodynia, neutrophil infiltration, oxidative stress, NLRP3 inflammasome and TRPV1 expression were examined.Eucalyptol attenuated MSU-induced mechanical allodynia and ankle edema in dose-dependent manners, with effectiveness similar to indomethacin. Eucalyptol reduced inflammatory cell infiltrations in ankle tissues. Eucalyptol inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine productions induced by MSU in ankle tissues in vivo. Eucalyptol reduced oxidative stress induced by MSU in RAW 264.7 cells in vitro as well as in ankle tissues in vivo, indicated by an increase in activities of antioxidant enzymes and reduction of reactive oxygen species. Eucalyptol attenuated MSU-induced upregulation of TRPV1 expression in ankle tissues and dorsal root ganglion neurons innervating the ankle. The in vivo effects of eucalyptol on ankle edema, mechanical allodynia, NLRP3 inflammasome, IL-1β and TRPV1 expression were mimicked by treating MSU-injected mice with anti-oxidants.Eucalyptol alleviates MSU-induced pain and inflammation via mechanisms possibly involving anti-oxidative effect. Eucalyptol and other anti-oxidants may represent promising therapeutic options for gout arthritis.