Abstract: Objective To investigate the analgesic effect of lappaconitine (LA) on burned rats and its supraspinal analgesic mechanism. Methods Male Sprague-Dawley rats were divided into 6 groups: normal, burn, burn LA，burn LA plus antisense oligodeoxynucleotide (A-ODN)，burn LA plus A317491 and burn LA plus ATP. The later 4 groups had LA (6mg/kg) administered intraperitoneally. The pain threshold was characterized by the mechanical withdrawal threshold (MWT) testing; The expression of P2X3 receptor protein in the midbrain periaqueductal gray (PAG) was assessed by Western blot analysis. Observation the intra-PAG injection of P2X3 A-ODN, selective antagonist and agonist of P2X3 receptor on the analgesic effect of LA. Results In burn group, the MWT was decreased while increased in burn LA group. LA induced a significantly up-regulated P2X3 receptor protein expression in PAG. The antinociceptive effect of LA was attenuated significantly by P2X3 A-ODN. The α,β-meATP or A317491 significantly enhanced or attenuated analgesic effect of LA, respectively. Conclusions LA produces an antinociceptive effect on burn pain via increases expression and function of P2X3 receptors in the PAG.

Key words: lappaconitine, burn pain, P2X3 receptor, midbrain periaqueductal gray