DIRECT EVIDENCE OF AN EXTENSIVE GABAERGIC INNERVATION OF THE SPINAL DORSAL HORN BY FIBERS DESCENDING FROM THE ROSTRAL VENTROMEDIAL MEDULLA

A long line of studies emphasizes the contribution of serotonergic fib res descending from the rostral ventromedial medulla in the control of spinal nociceptive information processing. A growing body of evidence , however, suggests that the relative contribution of serotonin to the mediation of spinal neuronal activity from the rostral ventromedial m edulla may require re-evaluation. It has recently been substantiated t hat, in addition to the serotonergic fibres, the spinal dorsal horn re ceives an abundant non-serotonergic projection from the rostral ventro medial medulla. Furthermore, stimulation in the rostral ventromedial m edulla could result in a powerful inhibition of nociceptive spinothala mic tract cells without any detectable serotonin release in the dorsal horn. After labelling raphe-spinal axons and axon terminals in the ra t by iontophoretic injections of the anterograde axonal tracer Phaseol us vulgaris leucoagglutinin into the central region of the rostral ven tromedial medulla (nucleus raphe magnus) and revealing GABA and glycin e immunoreactivites of the labelled raphe-spinal terminals and their p ostsynaptic targets by postembedding immunocytochemical methods, here we demonstrate an extensive GABAergic projection from the rostral vent romedial medulla to the spinal dorsal horn. We show that the majority of the labelled raphe-spinal terminals in laminae I-IIo and IV-V conta in GABA and some of the GABA-immunoreactive terminals are also immunor eactive for glycine. We also disclose that GABA-immunoreactive raphe-s pinal terminals establish synaptic contacts primarily with GABA- and g lycine-negative, presumably excitatory, spinal neurons, including Calb indin-D-28k- as well as parvalbumin-immunoreactive cells in both lamin ae I-IIo and IV-V. The results suggest that volleys in fibres descendi ng from the rostral ventromedial medulla may evoke GABA release from r aphe-spinal terminals, and the released GABA, in some cases probably a cting together with glycine, might play a crucial, as yet mostly unide ntified, role in the inhibition of nociceptive information processing in the dorsal horn of the spinal cord. Copyright (C) 1996 IBRO.