Scorpion Buthus martensi Karch (BmK) venom could induce severe ongoing pain,inflammation and burning sensation in human.In the present study,the extracellular signaling-regulated kinases (ERK) in spinal cord activated by intraplantar injection of BmK venom and the time course were investigated to clarify the central signal pathway involved in pain responses induced by the experimental scorpion BmK sting in rats.After the administration of BmK venom,p-ERK was found to express mainly in the superficial layers at the ipsilateral spinal cord LA-L5 segments.P-ERK began to appear at 2 min,reached a peak level at 30 min,maintained at 1 hour and decreased at 2 h and returned toward basal level at 4 h.To further test whether ERK activation contribute to persistent pain hypersensitivity,three doses of U0126 (0.1 pg,1 μg and 10 μg),a widely used specific MAP kinase kinase (MEK) inhibitor,were intrathecally injected by direct lumbar puncture at the L5-L6 spinal levels before intraplantar injection of BmK venom.It was found that tonic spontaneous pain,unilateral heat hypersensitivity and bilateral mechanical hypersensitivity induced by BmK venom could be partially suppressed by U0126.Therefore,activation of spinal ERK pathway was involved in pain-related behaviors induced by BmK venom.