Contralateral Heat Hyperalgesia Induced by Unilaterally Intraplantar Bee Venom Injection is Produced by Central Changes: a Behavioral Study in the Conscious Rat

In a previous study, we found that subcutaneous (s.c.) intraplantar injection of bee venom unilaterally could produce bilateral heat hyperalgesia. However, the bee venom-induced heat hyperalgesia identified in the injection site was presumed to be different from that identified in the contralateral hindpaw, since the former co-existed with the mechanical hyperalgesia while the latter did not. The aim of the present study was to testify whether the contralateral heat hyperalgesia identified in the bee venom model was a consequence of central changes. The radiant heat and von Frey-type filaments were applied to both the injection site and the contralateral pawpad of conscious rats prior to and 4 h after s.c. bee venom injection. After confirmation of the development of primary heat and mechanical hyperalgesia and contralateral heat hyperalgesia following s.c. bee venom, the sciatic nerve of the injection side was transected. After axotomy, the bee venom-induced heat hyperalgesia in the non-injected hindpaw was not altered at all compared with that prior to axotomy. Moreover, intrathecal pre-treatment with either N-methyl-D-aspartate (NMDA) or non-NMDA receptor antagonist could prevent the development of the contralateral heat hyperalgesia. The present results suggest that central sensitization contributes to development of the bee venom-induced contralateral heat hyperalgesia and activation of both NMDA and non-NMDA receptors in the spinal cord is involved in the processing.