Fiche publication
Date publication
juillet 2016
Journal
Pain
Auteurs
Membres identifiés du Cancéropôle Est :
Dr YALCIN CHRISTMANN Ipek
Tous les auteurs :
Medrano MC, Dhanasobhon D, Yalcin I, Schlichter R, Cordero-Erausquin M
Lien Pubmed
Résumé
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.
Mots clés
Acetazolamide, pharmacology, Action Potentials, drug effects, Animals, Carbonic Anhydrase Inhibitors, pharmacology, Disease Models, Animal, Mice, Neuralgia, physiopathology, Pain Threshold, drug effects, Physical Stimulation, Posterior Horn Cells, drug effects, Spinal Cord Dorsal Horn, drug effects
Référence
Pain. 2016 07;157(7):1432-1442
