Restoring ionotropic inhibition as an analgesic strategy.
Neuronal inhibition in nociceptive relays of the spinal cord is essential for the proper processing of nociceptive information. In the spinal cord dorsal horn, the activity of synaptic and extrasynaptic GABAA and glycine receptors generates rapid, Cl(-)-dependent neuronal inhibition. A loss of this ionotropic inhibition, particularly through the collapse of the inhibitory Cl(-)-gradient, is a key mechanism by which pathological pain conditions develop. This review summarizes the roles of ionotropic inhibition in the regulation of nociception, and explores recent evidence that the potentiation of GABAA or glycine receptor activity or the enhancement of inhibitory drive can reverse pathological pain.
Unité de neurosciences cellulaires et moléculaire, Centre de recherche de l'institut universitaire en santé mentale de Québec, Québec, Canada.
Robert P
RP
Bonin
Yves
Y
De Koninck
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D059225:Nociception / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D027981:Symporters; D000096922:K Cl- Cotransporters
Analgesia; Chloride; Dorsal horn; GABA; Glycine; KCC2