Effects of intrathecal injection of T-type calcium channel blockers in the rat formalin test

Abstract

T-type Ca2+ channels have been implicated in the induction of long-term potentiation, a synaptic plasticity involved in the central sensitization that contributes to the generation of inflammatory pain, in spinal sensory neurons. In this study, we examined the effects of intrathecal T-type Ca2+ channel blockers, mibefradil, ethosuximide and NiCl2, in the rat formalin test, an inflammatory pain model. Biphasic characteristic nociceptive behaviors were induced by intraplantar injection of formalin (5% formaldehyde, 50 microl) in Sprague-Dawley rats and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin injection. Intrathecal pretreatment with mibefradil (50-500 microg) and NiCl2 (1-10 microg) dose-dependently decreased the flinch numbers and biting and licking time in both phases. The ID50s of mibefradil in inhibiting the phases 1 and 2 flinch responses were 74.3+/-4.6 and 100.9+/-8.7 microg, respectively, and those of NiCl2 were 2.7+/-1.1 and 3.3+/-0.1 microg, respectively. Ethosuximide, at the doses up to 1200 microg, however, did not affect the nociceptive responses in both phases. It is suggested that spinal T-type Ca2+ channels may play a role in formalin-induced inflammatory pain. The ineffectiveness of ethosuximide is discussed.