The present study found that EA pre-treatment effectively attenuated both spinal ERK activation and hyperalgesia against carrageenan-induced inflammation, whereas EA co-treatment with carrageenan injection unexpectedly elevated ERK activation in a synergistic manner and virtually had no analgesic effect. Therefore, we have concluded that the molecular mechanism of EA anagesia may be related to the inhibition of spinal ERK activation. Further experiments are required to find the intermediate candidates which transmits the pain-alleviating signals on the way of inhibiting ERK activation by EA.