The role of spinal cord extrasynaptic α5GABAA receptors in chronic pain

Autor:	Guadalupe C. Vidal-Cantú, Jorge E. Torres-López, Ricardo Felix, Rodolfo Delgado-Lezama, Mariana Bravo-Hernández, Guadalupe Raya-Tafolla, Janet Murbartián, Yarim E. De la Luz-Cuellar, Alberto Vargas-Parada, Luis A. Martínez‐Zaldivar, Úrzula Franco-Enzástiga, Vinicio Granados-Soto, Crystell Guadalupe Guzmán-Priego, Erick J. Rodríguez‐Palma, Nara S. Alvarado‐Cervantes
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	GABAA and GABAB receptors GABAA receptor business.industry Physiology musculoskeletal neural and ocular physiology Chronic pain Pain medicine.disease Spinal cord Blockade Hoffmann reflex Allodynia medicine.anatomical_structure Nociception nervous system Physiology (medical) extrasynaptic GABAA receptors Hyperalgesia medicine QP1-981 medicine.symptom Receptor business Neuroscience
Zdroj:	Physiological Reports, Vol 9, Iss 16, Pp n/a-n/a (2021)
Popis:	Chronic pain is an incapacitating condition that affects a large population worldwide. Until now, there is no drug treatment to relieve it. The impairment of GABAergic inhibition mediated by GABAA receptors (GABAA R) is considered a relevant factor in mediating chronic pain. Even though both synaptic and extrasynaptic GABAA inhibition are present in neurons that process nociceptive information, the latter is not considered relevant as a target for the development of pain treatments. In particular, the extrasynaptic α5 GABAA Rs are expressed in laminae I-II of the spinal cord neurons, sensory neurons, and motoneurons. In this review, we discuss evidence showing that blockade of the extrasynaptic α5 GABAA Rs reduces mechanical allodynia in various models of chronic pain and restores the associated loss of rate-dependent depression of the Hoffmann reflex. Furthermore, in healthy animals, extrasynaptic α5 GABAA R blockade induces both allodynia and hyperalgesia. These results indicate that this receptor may have an antinociceptive and pronociceptive role in healthy and chronic pain-affected animals, respectively. We propose a hypothesis to explain the relevant role of the extrasynaptic α5 GABAA Rs in the processing of nociceptive information. The data discussed here strongly suggest that this receptor could be a valid pharmacological target to treat chronic pain states.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::06b10a03dc3bd1c60475d762fd57481c https://doaj.org/article/eea88a491b7c426fa95383be9dcc51ba Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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