title: Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II.
abstract: Nociceptive processing is tuned by GABAA receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 3α5α-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the contribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Measured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABAA IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5α-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABAA tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 3α5α-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds.
authors: Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, F-67084 Strasbourg, France; Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, 162A, avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors: Vivien
authors: V
authors: Zell
authors: Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, 162A, avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors: Ulrike
authors: U
authors: Hanesch
authors: Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, F-67084 Strasbourg, France.
authors: Pierrick
authors: P
authors: Poisbeau
authors: Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, 162A, avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors: Fernand
authors: F
authors: Anton
authors: Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, F-67084 Strasbourg, France. Electronic address: pdarbon@inci-cnrs.unistra.fr.
authors: Pascal
authors: P
authors: Darbon
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000097:blood*; D053444:Inhibitory Postsynaptic Potentials; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D066148:Spinal Cord Dorsal Horn / Q000254:growth & development*
chemical_list: D005938:Glucocorticoids; D011963:Receptors, GABA-A
keywords: GABA extrasynaptic transmission; GABA synaptic transmission; Glucocorticoids; Mechanical pain sensitivity; Spinal dorsal horn