To elucidate neurophysiological mechanisms of persistent pain induced by tissue injury, the present study was designed to investigate the effects of s.c. bee venom injection on responses of the dorsal horn nociceptive neurons and those of behavior in anesthetized and awake cats, respectively. A parallel comparative study was also performed to compare the effects of s.c. bee venom and formalin injections on neuronal responses by using an extracellular single-unit recording technique. The present results showed that s.c. bee venom injection into the peripheral cutaneous receptive field resulted in a protracted, tonic monophase of increase in spike responses of wide-dynamic-range (WDR) neurons for more than 1 h, while injection of the same volume of vehicle did not have such an effect. The mean number of spikes during the 60-min period after bee venom was 6.74+/-2.58 spikes/s (n=10), which showed a significant increase in firing rate over the background activity (2.23+/-0.96 spikes/s). Behavioral observations showed that s.c. bee venom injection into the dorsum of a hind paw also produced a prolonged, tonic single phase of response indicative of pain, suggesting that central neuronal changes may contribute to development of bee venom-induced prolonged, tonic pain in cats. The increased neuronal firing induced by s.c. bee venom could be suppressed by a single dose of i.v. morphine and resumed by naloxone. Blockade of the sciatic nerve with lidocaine resulted in a complete suppression of the bee venom-induced neuronal firing, suggesting that the central neuronal changes following s.c. bee venom are peripherally-dependent. Comparative studies showed that the duration and frequency of the bee venom-induced neuronal responses were comparable to those induced by s.c. formalin; however, responses of WDR neurons to mechanical stimuli applied to the injection site of the two chemical agents were quite different. Bee venom produced a significant enhancement of mechanical responses of WDR neurons, while, on the contrary, formalin produced a desensitization of sensory receptors in the injection site, suggesting that the two tonic pain models may have different underlying mechanisms. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.