Effect of tetrahydropalmatine analogs on Fos expression induced by formalin-pain

AIM: To study the effect of tetrahydropalmatine (THP) analogs on Fos protei n expression induced by formalin-pain and elucidate analgesic mechanism of THP analogs. METHODS: The pain response to Sprague Dawley rats was induced with formalin injected sc into the plantar surface of the right hindpaw. Fo s protein expression in brain and spinal cord was investigated with immunoh istochemistry. The numbers of Fos-like immunoreactive (FLI) neurons were co unted with Leica Q570 image analyzer. RESULTS: In the groups of THP analogs and D-2 antagonist spiperone, FLI: neurons induced by intraperitoneal tip) injection of THP analogs and spiperone were mainly located in the striatum and accumbens nucleus, and a few FLI neurons were also in sensorimotor cor tex. In the D-1 antagonist, D1 agonist, D2 agonist, saline and vehicle grou ps, FLI neurons were seldom seen in the striatum and accumbens nucleus. Mor eover, the Fos protein expression induced by I-THP and spiperone could be p revented by the pretreatment of the D-2 agonist quinpirole but not D-1 agon ist SKF38393. Ln the formalin-pain group, FLI neurons were mainly distribut ed in ascending pain afferent system (APAS) and descending pain modulation system (DPMS). Following ip THP analogs, however, the numbers of FLI neuron s induced by formalin-pain in the APAS, such as dorsal horn (mainly laminae I, II, IV - VI were markedly decreased, while the numbers of FLI neurons i n the DPMS, such as periaqueductal gray ( FAG) and reticular paragigantocel lular lateral nucleus (RPLN) were significantly increased. CONCLUSION: THP analogs enhanced the activity of brainstem DPMS by the blockade of D-2 rece ptors in the striatum and accumbens nucleus, and sequentially inhibited the inputs of peripheral pain afferent message in spinal cord level.