Lamotrigine effectively blocks synaptic transmission between nociceptive primary afferents and secondary sensory neurons in the rat superficial spinal dorsal horn

Abstract It has been demonstrated that in the superficial spinal dorsal horn, Lamotrigine, which is known to block voltage-sensitive Na+ and Ntype Ca2+ channels, depresses neural activities evoked by sustained activation of nociceptive primary afferent fibres. In the present experiments, we study how Lamotrigine exerts its inhibitory effect on spinal nociceptive information-processing mechanisms. We show that Lamotrigine in an in vitro slice preparation effectively blocks synaptic transmission between primary afferents and secondary sensory neurons. Together with the robust increase in the failure rate and reduction in the amplitude of excitatory post-synaptic potentials (EPSPs) evoked by stimulation of nociceptive primary afferents, Lamotrigine causes a marked decrease in the number and amplitude of spontaneous EPSPs and a gradual shift of the resting membrane potential towards hyperpolarization. In addition, Lamotrigine treatment also changes the intrinsic firing pattern of superficial dorsal horn neurons. The results suggest that the effect of Lamotrigine on spinal nociceptive information-processing mechanisms is multiple: it depresses synaptic inputs from nociceptive primary afferents to secondary spinal sensory neurons and also weakens the intrinsic activities of nociceptive spinal neural circuits in the superficial spinal dorsal horn.