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

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. Pre‐ and post‐treatment with paeonol (30, 50 or 100 mg kg −1 , i.p.) dose‐dependently inhibited the carrageenan‐evoked thermal hyperalgesia. Treatment with paeonol dose‐dependently inhibited tumour necrosis factor‐ α (TNF‐ α ) and interleukin‐l β (IL‐1 β ) 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. 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. Elevated myeloperoxidase activity, an indicator of neutrophil infiltration, in carrageenan‐injected paws was also dose‐dependently reduced in paeonol‐treated rats. 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.British Journal of Pharmacology (2003) 139 , 1146–1152. doi: 10.1038/sj.bjp.0705360