Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat: a comparative study with the formalin test.

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 biphasic followed by a permanent hypoalgesia or analgesia in the formalin injection area although the duration and response intensity of spontaneous pain was comparable with those following bee venom treatment. Subcutaneous. bee venom injection also produced a distinct reduction of heat latency on the contralateral hindpaw, while s.c. formalin did not. On the other hand, s.c. bee venom injection produced a striking edema and redness of the plantar surface for nearly the same period as the development of hyperalgesia, while the edema and redness could not be obviously observed after the formalin treatment. In the control study, repetitive suprathreshold mechanical or heat stimuli applied to the plantar surface with or without saline treatment did not significantly influence the mechanical threshold or heat latency, suggesting that the phenomena of mechanical and heat hyperalgesia were not the effects of vehicle treatment or those of the stimulus modalities themselves. Taken together, our present results showed that in contrast to s.c. formalin injection, subcutaneous. bee venom injection produced little tissue damage but a striking inflammation accompanied by a prolonged spontaneous pain and a pronounced primary hyperalgesia to mechanical and heat stimuli in the treated hindpaw and a heat, but not mechanical, hyperalgesia in the contralateral hindpaw, implicating that bee venom model may have more advantages over the formalin test and probably other chemoirritants to study the neural mechanisms underlying pathological pain and, especially, the relationship between spontaneous pain and development of hyperalgesia.