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To elucidate the underlying mechanisms of pathological pain, it is important and necessary to develop an animal model characterized by both spontaneous tonic pain and hyperalgesia with a prolonged duration post-tissue injury. In this report, we investigated whether the two animal models of spontaneous tonic pain (the formalin test and the bee venom test) could develop a hyperalgesia to mechanical and thermal stimuli in the injured area following subcutaneous (s.c.) administration of the two chemical agents into the plantar surface of one hindpaw in the conscious rats. It was found that the persistent nociceptive response (flinching and lifting/licking the injected hindpaw) was monophasic and lasted for 1–2 h followed by a 72–96 h period of reduction in mechanical threshold and heat latency of withdrawal reflex in the bee venom injection area; however, in contrast, the spontaneous pain-related response was …