GABA_B Receptors Do Not Mediate the Inhibitory Actions of Gabapentin on the Spinal Reflex in Rats

Abstract

The clinical effectiveness of gabapentin for the treatment of epilepsy, spasticity, and neuropathic pain has been established. The mechanisms responsible for those actions, however, are still not clearly understood. We have recently demonstrated that gabapentin reduces the spinal reflex in rats via mechanisms that do not involve γ-aminobutyric acid (GABA)_A receptors. In the study, we attempted to explore the involvement of GABA_B receptors in gabapentin-induced inhibition of the spinal reflexes in spinalized rats. Stimulation of the dorsal root at L5 elicited the segmental mono-(MSR) and polysynaptic reflex (PSR) in the ipsilateral ventral root. The microinjection of gabapentin (1.5 and 5 nmol) into the ventral horn reduced both MSR and PSR, whereas the injection into the dorsal horn only inhibited the PSR, indicating that systemic gabapentin inhibits the MSR at the ventral horn and it inhibits the PSR at both the ventral and dorsal horns. The GABA_B-receptor antagonist CGP35348 (0.5 nmol) injected into the ventral horn antagonized the inhibition of the spinal reflexes by the GABA_B-receptor agonist baclofen (i.v.) but not by gabapentin (i.v.). Thus, GABA_B receptors do not appear to contribute to the gabapentin-induced inhibition of the spinal reflex.