Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats.

The present study was undertaken to elucidate the antinociceptive effect of intrathecal administration of huwentoxin-I (HWTX-I), a N-type calcium channel blocker from the venom of the Chinese bird spider Ornithoctonus huwena (Wang) [=Selenocosmia huwena wang], by comparison with omega-Conotoxin-MVIIA (omega-CTX-MVIIA) and morphine hydrochloride in the formalin test in conscious rats. Similar to omega-CTX-MVIIA and morphine, intrathecal pre-treatment with HWTX-I resulted in suppression of nociceptive behavior in a dose-dependent manner. The ED50 values of HWTX-I and omega-CTX-MVIIA were 0.28 and 0.19 microg/kg, respectively. It was also found that, at lower doses (0.1 and 0.5 microg/kg), the antinociceptive effect of HWTX-I was identical to that of omega-CTX-MVIIA, while omega-CTX-MVIIA acted more remarkably than HWTX-I at higher dose (1.0 microg/kg). However, the antinociception induced by omega-CTX-MVIIA were companied with motor dysfunction, and these side-effects became more evident with the doses of omega-CTX-MVIIA increasing. In contrast, HWTX-I did not show these side-effects at the doses of 0.5-1.0 microg/kg. Compared with HWTX-I and omega-CTX-MVIIA, the analgesic effect of intrathecal morphine hydrochloride was initiated faster, but lasted for a shorter time (about 2-3 h at 1.0 microg/kg) than that of HWTX-I and omega-CTX-MVIIA (about 4- 5 h at 1.0 microg/kg). Therefore, the present results show that, like omega-CTX-MVIIA, the intrathecal administration of HWTX-I is effective in antinociception in the rat model of the formalin test.