Our previous studies have established the idea that different types of
pain induced by subcutaneous
bee venom (BV) injection might be mediated by different spinal signaling pathways. To further testify this hypothesis, the present investigation was designed to detect whether spinal p38 and
c-Jun N-terminal kinase (JNK) pathways are equally or differentially involved in the development of persistent spontaneous nociception (PSN), primary heat and
mechanical hyperalgesia, and mirror-image heat (MIH)
hypersensitivity in the BV model, by evaluating the effects of intrathecal (i.t.) pre-administration of a p38 inhibitor SB239063 and a JNK inhibitor
SP600125 in the conscious rat. The results showed that i.t. pre-treatment with either SB239063 or
SP600125 caused a significant prevention of BV-induced persistent paw flinching reflex in a dose-related manner, with the former exhibiting much stronger inhibition than the latter. Moreover, the same doses of SB239063 and
SP600125 also exhibited different suppressive actions on the induction of primary heat
hyperalgesia and MIH
hypersensitivity. That is,
SP600125 produced a larger increase of thermal latency than SB239063 in the injected paw, whereas SB239063 mainly affected the value measured in the non-injected paw. Pre-treatment with neither SB239063 nor
SP600125 had any effect on BV-evoked
mechanical hyperalgesia. Taken together, these data suggest that activation of p38 in the spinal cord preferentially contributes to the development of PSN and MIH
hypersensitivity under pathological state, while spinal JNK signaling pathways might play more important roles in inducing primary heat
hyperalgesia.