Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia.

1. Paeonol was tested for its anti-inflammatory and analgesic effects in a rat model of carrageenan-evoked thermal hyperalgesia. The possible mechanisms involved in these effects were also investigated. 2. Pre- and post-treatment with paeonol (30, 50 or 100 mg kg(-1), i.p.) dose-dependently inhibited the carrageenan-evoked thermal hyperalgesia. 3. Treatment with paeonol dose-dependently inhibited tumour necrosis factor-alpha (TNF-alpha) and interleukin-lbeta (IL-1beta) formation, but enhanced IL-10 production in the rat paw exudates both at the early (1.5 h) and late phase (4 h) after carrageenan injection. However, inhibition of IL-6 formation by paeonol was only observed at the late phase. 4. Paeonol dose-dependently decreased the formation of prostaglandin E(2) (PGE(2)) in rat paw exudates with a greater inhibition at the late phase. However, inhibition of nitrate generation was observed only during the late phase (at 4 h after carrageenan injection), accompanied by an attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in paw tissue. 5. Elevated myeloperoxidase activity, an indicator of neutrophil infiltration, in carrageenan-injected paws was also dose-dependently reduced in paeonol-treated rats. 6. Our results suggest that the mechanisms by which paeonol exerts its anti-inflammatory and analgesic effects in this inflammatory model may be associated with decreased production of proinflammatory cytokines, NO and PGE(2) and increased production of IL-10, an anti-inflammatory cytokine, in carrageenan-injected rat paws. In addition, attenuation of the elevated iNOS and COX-2 protein expression as well as neutrophil infiltration in carrageenan-injected paws may also be involved in the beneficial effects of paeonol.