The Antiallodynic Action Target of Intrathecal Gabapentin: Ca2+ Channels, KATP Channels or N-Methyl-d-Aspartic Acid Receptors?

In Brief Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, N-methyl-d-aspartic acid (NMDA) receptors, and Ca2+ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before and after incision and after intrathecal drug administration. The antiallodynic effect of gabapentin (100 μg) was not affected by intrathecal pretreatment with antagonists of KATP channels, NMDA receptors or gamma-aminobutyric acid (GABA)A receptors. KATP channel openers and GABAA receptor agonist, per se, had little effect on the postincision allodynic response. The Ca2+ channel blocker of N-type (ω-conotoxin GVIA, 0.1–3 μg), but not of P/Q-type (ω-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and ω-conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca2+ channel activator. These results provide correlative evidence to support the contention that N-type Ca2+ channels, but not KATP channels or NMDA or GABAA receptors, might be involved in the antiallodynic effect of intrathecal gabapentin. IMPLICATIONS: Using a rat model of postoperative pain, this study explored the roles of adenosine triphosphate-sensitive K+ (KATP) channels, N-methyl-d-aspartic acid NMDA receptors, and Ca2+ channels in the antinociceptive action of intrathecal gabapentin. It is suggested that spinal N-type Ca2+ channels, but not KATP channels or NMDA receptors, might be involved in the gabapentin-induced analgesic effect.