Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test

Abstract

Background and objective: Gabapentin, an anticonvulsant with analgesic effect, has been reported to be an activator of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In this study, we tested the effect of intrathecal ZD7288, an HCN channel inhibitor, and its interaction with intrathecal gabapentin in the rat formalin test.

Methods: Male Sprague-Dawley rats (250-300 g) with an intrathecal catheter were intraplantarly injected with formalin (5% formaldehyde, 50 microl) in the right hindpaw. Ten minutes before formalin injection, gabapentin (100 or 200 microg) was given intrathecally. ZD7288 (50 microg) was administered intrathecally 10 min before paw formalin injection or intrathecal gabapentin. The paw flinch numbers in 1 min were counted at the first minute and every 5 min for 1 h after formalin injection.

Results: Biphasic flinching responses were induced by formalin and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin injection. Gabapentin (100 and 200 microg), given intrathecally 10 min before formalin injection, attenuated the flinching response during phase 2 of the formalin test. ZD7288 (50 microg), given intrathecally 10 min before formalin injection or intrathecal gabapentin injection, did not attenuate the formalin-induced flinching response or reverse gabapentin-induced analgesia.

Conclusion: Our data suggest that activation of spinal or dorsal root ganglion HCN channels or both is not involved in formalin-induced pain, and intrathecal gabapentin does not act as an HCN channel activator to achieve its antinociceptive effect in the formalin test.