title: Loss of inhibitory tone on spinal cord dorsal horn spontaneously and nonspontaneously active neurons in a mouse model of neuropathic pain.
abstract: Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed to be a key mechanism responsible for pain hypersensitivity in neuropathic pain syndromes. We evaluated this plasticity by recording responses to mechanical stimuli in silent neurons (nonspontaneously active [NSA]) and neurons showing ongoing activity (spontaneously active [SA]) in the SDH of control and nerve-injured mice (cuff model). The SA and NSA neurons represented 59% and 41% of recorded neurons, respectively, and were predominantly wide dynamic range (WDR) in naive mice. Nerve-injured mice displayed a marked decrease in the mechanical threshold of the injured paw. After nerve injury, the proportion of SA neurons was increased to 78%, which suggests that some NSA neurons became SA. In addition, the response to touch (but not pinch) was dramatically increased in SA neurons, and high-threshold (nociceptive specific) neurons were no longer observed. Pharmacological blockade of spinal inhibition with a mixture of GABAA and glycine receptor antagonists significantly increased responses to innocuous mechanical stimuli in SA and NSA neurons from sham animals, but had no effect in sciatic nerve-injured animals, revealing a dramatic loss of spinal inhibitory tone in this situation. Moreover, in nerve-injured mice, local spinal administration of acetazolamide, a carbonic anhydrase inhibitor, restored responses to touch similar to those observed in naive or sham mice. These results suggest that a shift in the reversal potential for anions is an important component of the abnormal mechanical responses and of the loss of inhibitory tone recorded in a model of nerve injury-induced neuropathic pain.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Medrano
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Dhanasak
authors.initials: D
authors.lastname: Dhanasobhon
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.
authors.forename: Ipek
authors.initials: I
authors.lastname: Yalcin
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.|Université de Strasbourg, Strasbourg, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Schlichter
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.|University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.
authors.forename: Matilde
authors.initials: M
authors.lastname: Cordero-Erausquin
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D009437:Neuralgia / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide