학술논문
The role of spinal cord extrasynaptic α5GABAA receptors in chronic pain
Document Type
Report
Author
Delgado‐Lezama, Rodolfo; Bravo‐Hernández, Mariana; Franco‐Enzástiga, Úrzula; De La Luz‐Cuellar, Yarim E.; Alvarado‐Cervantes, Nara S.; Raya‐Tafolla, Guadalupe; Martínez‐Zaldivar, Luis A.; Vargas‐Parada, Alberto; Rodríguez‐Palma, Erick J.; Vidal‐Cantú, Guadalupe C.; Guzmán‐Priego, Crystell G.; Torres‐López, Jorge E.; Murbartián, Janet; Felix, Ricardo; Granados‐Soto, Vinicio
Source
Physiological Reports. August 2021, Vol. 9 Issue 16
Subject
Language
English
Abstract
INTRODUCTION The circuit processing nociceptive information located mainly in laminae I–III of the spinal cord's dorsal horn contains, among other cells, projection neurons, GABAergic, glycinergic, and glutamatergic interneurons, Aβ, Aδ, [...]
: 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 GABA[sub.A] receptors (GABA[sub.A]R) is considered a relevant factor in mediating chronic pain. Even though both synaptic and extrasynaptic GABA[sub.A] 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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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.
: 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 GABA[sub.A] receptors (GABA[sub.A]R) is considered a relevant factor in mediating chronic pain. Even though both synaptic and extrasynaptic GABA[sub.A] 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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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 α[sub.5]GABA[sub.A]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.