Mechanisms for the Anti-nociceptive Actions of the Descending Noradrenergic and Serotonergic Systems in the Spinal Cord

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The sensation of pain plays a critical role as an alert and as a protection system against tissue damage from mechanical, chemical, and thermal stimuli. Despite the protective role of pain, the severity of pain sensation is markedly attenuated by the endogenous pain inhibitory systems that predominantly originate at the brain stem. Both behavioral and in vivo extracellular recording studies have sought the loci producing analgesia and clarification of the anti-nociceptive actions. Among those loci, the main descending systems to the spinal dorsal horn are noradrenergic and serotonergic. Although, in vivo studies have provided basic knowledge of these systems, the precise synaptic mechanisms underlying the analgesic actions have not yet been elucidated until recently. The newly developed in vitro slice and in vivo patch-clamp recordings have disclosed the synaptic mechanisms of the noradrenergic and serotonergic effects at the level of spinal dorsal horn. This paper reviews the anti-nociceptive action of these systems, while particularly focusing on the electrophysiological aspects of the systems at the single neuron level in the spinal dorsal horn as well as their origins and responsible receptor subtypes.