Participation of K(ATP) Channels in the Antinociceptive Effect of Pregabalin in Rat Formalin Test

Abstract

BACKGROUND: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-Ca(2+)-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with K(ATP) channels in the rat formalin test.

METHODS: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250-300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) 20 µl (CON group); pregabalin 0.3, 1, 3 and 10 µg in NS 10 µl (PGB group); glibenclamide 100 µg in DMSO 5 µl with pregabalin 0.3, 1, 3 and 10 µg in NS 5 µl (GBC group). All the drugs were flushed with NS 10 µl. Immunohistochemistry for the K(ATP) channel was done with a different set of rats divided into naïve, NS and PGB groups.

RESULTS: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the K(ATP) channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test.

CONCLUSIONS: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the K(ATP) channel. However, pregabalin did not induce K(ATP) channel expression in the spinal cord dorsal horn.