Cargando…

Neuropathic Injury–Induced Plasticity of GABAergic System in Peripheral Sensory Ganglia

GABA is a major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Inhibitory GABA(A) channel circuits in the dorsal spinal cord are the gatekeepers of the nociceptive input from the periphery to the CNS. Weakening of these spinal inhibitory mechanisms is a hallmark of chroni...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Caixue, Hao, Han, He, Kaitong, An, Yating, Pu, Zeyao, Gamper, Nikita, Zhang, Hailin, Du, Xiaona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354334/
https://www.ncbi.nlm.nih.gov/pubmed/34385921
http://dx.doi.org/10.3389/fphar.2021.702218
Descripción
Sumario:GABA is a major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Inhibitory GABA(A) channel circuits in the dorsal spinal cord are the gatekeepers of the nociceptive input from the periphery to the CNS. Weakening of these spinal inhibitory mechanisms is a hallmark of chronic pain. Yet, recent studies have suggested the existence of an earlier GABAergic “gate” within the peripheral sensory ganglia. In this study, we performed systematic investigation of plastic changes of the GABA-related proteins in the dorsal root ganglion (DRG) in the process of neuropathic pain development. We found that chronic constriction injury (CCI) induced general downregulation of most GABA(A) channel subunits and the GABA-producing enzyme, glutamate decarboxylase, consistent with the weakening of the GABAergic inhibition at the periphery. Strikingly, the α5 GABA(A) subunit was consistently upregulated. Knock-down of the α5 subunit in vivo moderately alleviated neuropathic hyperalgesia. Our findings suggest that while the development of neuropathic pain is generally accompanied by weakening of the peripheral GABAergic system, the α5 GABA(A) subunit may have a unique pro-algesic role and, hence, might represent a new therapeutic target.