Mechanisms of Impaired Inhibition in the Spinal Dorsal Horn

Current Topics in Pain: 12th World Congress on Pain edited by José Castro-Lopes IASP Press, Seattle, © 2009 53 It is a general rule that in the nervous system, all forms of activation are balanced by some kind of inactivation or inhibition. Th is principle also applies, of course, to all levels of the nociceptive system, from the activation of nociceptive Aδ or C fi bers to the excitation of nociceptive neurons in the spinal dorsal horn and the brain. Th is chapter focuses on spinal mechanisms of inhibition, but it is likely that similar fi ndings also apply to the processing of nociceptive information in the trigeminal system and to supraspinal nociception. In the dorsal horn of the spinal cord, about 30–40% of all neurons are inhibitory [51], using γ-aminobutyric acid (GABA) as their fast inhibitory neurotransmitter, which acts on ionotropic GABAA or G-protein-coupled metabotropic GABAB receptors. A signifi cant proportion of these neurons use glycine as a cotransmitter, which acts on ionotropic glycine receptors (see also Chapter 3 by Todd, this volume). Inhibitory spinal interneurons may also use endogenous opioids, and supraspinal descending fi ber systems may further use monoamines as neurotransmitters to modulate spinal nociception [30,42]. Th e peptidergic and monoaminergic systems are not considered here. Spinal Th e Role of Inhibition in the Generation and Amplifi cation of Pain