In:
Journal of Neuroscience Research, Wiley, Vol. 95, No. 6 ( 2017-06), p. 1307-1318
Abstract:
Neuronal inhibition mediated by GABA A receptors constrains nociceptive processing in the spinal cord, and loss of GABAergic inhibition can produce allodynia and hyperalgesia. Extrasynaptic α5 subunit‐containing GABA A receptors (α5GABA A Rs) generate a tonic conductance that inhibits neuronal activity and constrains learning and memory; however, it is unclear whether α5GABA A Rs similarly generate a tonic conductance in the spinal cord dorsal horn to constrain nociception. We assessed the distribution of α5GABA A Rs in the spinal cord dorsal horn by immunohistochemical analysis, and the activity and function of α5GABA A Rs in neurons of the superficial dorsal horn using electrophysiological and behavioral approaches in male, null‐mutant mice lacking the GABA A R α5 subunit ( Gabra5−/− ) and wild‐type mice (WT). The expression of α5GABA A Rs in the superficial dorsal horn followed a laminar pattern of distribution, with a higher expression in lamina II than lamina I. Similarly, the tonic GABA A current in lamina II neurons had a larger contribution from α5GABA A Rs than in lamina I, with no significant contribution of these receptors to synaptic GABA A current. In behavioural tests, WT and Gabra5−/− mice exhibited similar acute thermal and mechanical nociception, and similar mechanical sensitization immediately following intraplantar capsaicin or Complete Freund's Adjuvant (CFA). However, Gabra5−/− mice showed prolonged recovery from sensitization in these models, and increased responses in the late phase of the formalin test. Overall, our data suggest that tonically‐active α5GABA A Rs in the spinal cord dorsal horn accelerate the resolution of hyperalgesia and may therefore serve as a novel therapeutic target to promote recovery from pathological pain. © 2016 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0360-4012
,
1097-4547
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
1474904-X
SSG:
12
