The purpose of the present study was to explore the analgesic effects of the low 
voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and 
mibefradil in persistent and acute nociceptive tests. The anticonvulsant effects 
of the compounds were also determined in the intravenous pentylenetetrazol 
seizure model. Following intraperitoneal administration, ethosuximide and 
trimethadione dose-dependently reversed capsaicin-induced mechanical 
hyperalgesia. Similarly, the highest dose of mibefradil tested (30 microg, 
intracisternal) reversed capsaicin-induced mechanical hyperalgesia. Ethosuximide 
and mibefradil produced statistically significant analgesic effects in both 
early and late phase formalin-induced behaviors and trimethadione reduced late 
phase behaviors. Additionally, ethosuximide and trimethadione produced 
antinociceptive effects in the rat-tail flick reflex test. In contrast, 
following intracisternal administration, mibefradil had no effect in the tail 
flick reflex test. In addition, the anticonvulsants ethosuximide and 
trimethadione increased the doses of pentylenetetrazol required to produce both 
first twitch and clonic seizures. In contrast however, mibefradil had no 
anticonvulsant effect. The present results demonstrate that the clinically used 
anticonvulsants ethosuximide and trimethadione provide analgesic effects at 
doses, which are anticonvulsant. Furthermore, the data further supports the idea 
that T-type Ca2+ channels may be important targets for treating persistent pain 
syndromes.