GABAA receptor-mediated excitation of nociceptive afferents in the rat isolated spinal cord-tail preparation.
Algogens such as capsaicin, bradykinin, acetylcholine, 5-hydroxytryptamine and potassium ions applied to exposed tail skin of the rat isolated spinal cord-tail preparation evoke a ventral root response consisting of depolarization and spiking activity. L-glutamate and kainate also evoke similar reflexes. All these compounds evoke depolarization of afferent axons or dorsal root ganglion cells. Since GABA depolarizes unmyelinated afferent fibers, the ability of GABA receptor agonists to activate cutaneous nociceptive afferents has been examined. GABA superfused over exposed tail skin evoked a ventral root reflex essentially identical to that produced by capsaicin (3 microM). The EC50 was 27 microM. Muscimol, 3-aminopropane sulphonate, isoguvacine and beta-alanine had effects comparable to GABA, with EC50 values of 9.6, 26, 56 and 870 microM respectively. Baclofen (100 microM) or glycine (10 mM) had no effect. Bicuculline applied to the tail competitively antagonized GABA (Schild slope = -1.03) with a pA2 of 5.8. Spinal application of 1 microM morphine blocked the actions of GABA and capsaicin. These data indicate that GABAA receptors can depolarize and excite nociceptive afferents. GABA could be involved in nociception by contributing to firing of C-fibres, or by analogy to presynaptic inhibition in the spinal cord, may act to decrease neuropeptide transmitter release in cutaneous tissue.
Ault
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Department of Neurosciences, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426-0900.
Hildebrand
L M
LM
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D004566:Electrodes; D018756:GABA Antagonists; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017459:Receptors, Amino Acid / Q000037:antagonists & inhibitors / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013623:Tail / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D017459:Receptors, Amino Acid; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D002211:Capsaicin