► P2X7 receptor antagonist inhibited BV-induced persistent spontaneous nociception and mechanical allodynia. ► P2X7 receptor antagonist had no effect on BV-induced inflammatory edema. ► Spinal P2X7 receptors contribute to BV-induced nociception, but not inflammation. Recently, P2X7 receptor (P2X7R) has been found to contribute to the development of inflammatory pain, however, the role of spinal P2X7R is not clear. The present study was designed to determine the roles of spinal P2X7R in the bee venom (BV) model, characterized by multiple pain-related behaviors and obvious inflammatory edema. We determined the effects of P2X7R antagonist A438790 on BV-induced PSN, mechanical allodynia and inflammatory swelling. Pre-treatment with intrathecal administration of A438079 significantly inhibited BV-induced PSN and mechanical allodynia in a dose-dependent manner, but had no effect on BV-induced inflammatory swelling. These data suggest that the activation of spinal P2X7Rs may play a key role in BV-induced nociception, but not inflammation.