The role of spinal cord extrasynaptic α
            <sub>5</sub>
            GABA
            <sub>A</sub>
            receptors in chronic pain

Delgado‐Lezama, Rodolfo; Bravo‐Hernández, Mariana; Franco-Enzástiga, Úrzula; Luz-Cuellar, Yarim Elideth De la; 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 Guadalupe; Torres-López, Jorge Elías; Murbartián, Janet; Felix, Ricardo; Granados‐Soto, Vinicio

doi:10.14814/phy2.14984

Cited by 9 publications

(7 citation statements)

References 57 publications

(94 reference statements)

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“…Distinct DNA methylation and hormonal adaptations are associated with these observations. These results suggest the α5-containing GABAARs putative targets of chronic pain in females ( Delgado-Lezama et al, 2021 ; Franco-Enzástiga et al, 2021 ).…”

Section: Emerging Roles Of Cys-loop Receptors In the Target Space Of ...mentioning

confidence: 71%

“…However, they may play a pro-nociceptive role at late stages of inflammation and are putative targets for chronic and neuropathic pain. Blocking of α5-containing GABAARs has been found to reduce chronic pain in animal models ( Delgado-Lezama et al, 2021 ). Interestingly, sex-dependent effects have been observed in the reduction of stress-induced behaviors, and in chronic pain, both linked to α5-containing GABAARs modulation.…”

Section: Emerging Roles Of Cys-loop Receptors In the Target Space Of ...mentioning

confidence: 99%

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Cys-loop receptors on cannabinoids: All high?

et al. 2022

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Endocannabinoids (eCBS) are endogenously derived lipid signaling molecules that serve as tissue hormones and interact with multiple targets, mostly within the endocannabinoid system (ECS). The ECS is a highly conserved regulatory system involved in homeostatic regulation, organ formation, and immunomodulation of chordates. The term “cannabinoid” evolved from the distinctive class of plant compounds found in Cannabis sativa, an ancient herb, due to their action on CB1 and CB2 receptors. CB1/2 receptors are the primary targets for eCBs, but their effects are not limited to the ECS. Due to the high interest and extensive research on the ECS, knowledge on its constituents and physiological role is substantial and still growing. Crosstalk and multiple targeting of molecules are common features of endogenous and plant compounds. Cannabimimetic molecules can be divided according to their origin, natural or synthetic, including phytocannabinoids (pCB’s) or synthetic cannabinoids (sCB’s). The endocannabinoid system (ECS) consists of receptors, transporters, enzymes, and signaling molecules. In this review, we focus on the effects of cannabinoids on Cys-loop receptors. Cys-loop receptors belong to the class of membrane-bound pentameric ligand gated ion channels, each family comprising multiple subunits. Mammalians possess GABA type A receptors (GABAAR), glycine receptors (GlyR), serotonin receptors type 3 (5-HT3R), and nicotinic acetylcholine receptors (nAChR). Several studies have shown different modulatory effects of CBs on multiple members of the Cys-loop receptor family. We highlight the existing knowledge, especially on subunits and protein domains with conserved binding sites for CBs and their possible pharmacological and physiological role in epilepsy and in chronic pain. We further discuss the potential for cannabinoids as first line treatments in epilepsy, chronic pain and other neuropsychiatric conditions, indicated by their polypharmacology and therapeutic profile.

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Section: Emerging Roles Of Cys-loop Receptors In the Target Space Of ...mentioning

confidence: 71%

Section: Emerging Roles Of Cys-loop Receptors In the Target Space Of ...mentioning

confidence: 99%

Cys-loop receptors on cannabinoids: All high?

et al. 2022

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“…6,12,19,27,41,43,60 It has been widely reported that GABA A receptors expressed in the spinal cord regulate sensory information. 13,19,27,29,80 Previous work has shown that the a 6 subunit is expressed in lamina II of the spinal dorsal horn. 13 However, we detected it throughout all laminae, ranging from lamina II to lamina V. Other studies have reported the expression of the a 6 subunit in the trigeminal ganglion of rats.…”

Section: Discussionmentioning

confidence: 99%

“…19,27,29,51 It has been hypothesized that restoring GABAergic tone by modulating the function of extra synaptic GABA A receptors may be beneficial for pain management. 13,66,67,79 GABA A receptors are ligand-dependent channels. There are 19 GABA A subunits up to date, and each one confers classical pharmacological or biophysical properties.…”

Section: Introductionmentioning

confidence: 99%

Activation of α6-containing GABAA receptors induces antinociception under physiological and pathological conditions

Rodríguez‐Palma

Luz-Cuellar

Islas-Espinoza

et al. 2022

PAIN

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“…Finally, GABA is the main inhibitory neurotransmitter, and its receptors are found in the thalamus, spinal cord and cortex [ 29 ]. A decrease in GABA levels by selectively activating GABA(B)-receptor-bearing rostral agranaular insular cortex neurons at the insula increases pain through projections to the amygdala, while preventing its degradation by using an enzyme inhibitor or gene transfer mediated by a viral vector relieves it by enhancing the descending inhibition of spinal nociceptive neurons, suggesting its key role in the pathophysiology of some chronic pain conditions [ 28 ].…”

Section: Cortical Changes In Chronic Low Back Painmentioning

confidence: 99%

Structural, Functional and Neurochemical Cortical Brain Changes Associated with Chronic Low Back Pain

Medrano-Escalada

Plaza-Manzano

Fernández‐de‐las‐Peñas

et al. 2022

Tomography

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Chronic low back pain (CLBP) is one of the most prevalent musculoskeletal disorders, being one of the leading contributors to disability worldwide and involving an important economic and social burden. Up to 90% of CLBP is non-specific (not associated with specific injuries), with a chronicity expectation estimated at 10%. Currently, motivational and emotional central circuits are being investigated due to their role in CLBP persistency and chronification. Therefore, this narrative review aimed to summarize the evidence regarding the cortical brain changes described for proposing novel multidisciplinary approaches. Novel advances in neuroimaging techniques demonstrated structural (e.g., decrease in the grey matter located at the dorsolateral prefrontal cortex), functional (e.g., connectivity impairments in those areas involved in pain processing), and neurochemical changes (e.g., decrease in cerebral metabolites). In addition, significant changes were found in the primary somatosensory and motor cortex, contributing to the alteration of low back muscles activation and function.

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The role of spinal cord extrasynaptic α ₅ GABA _A receptors in chronic pain

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 57 publications

Cys-loop receptors on cannabinoids: All high?

Cys-loop receptors on cannabinoids: All high?

Activation of α6-containing GABAA receptors induces antinociception under physiological and pathological conditions

Structural, Functional and Neurochemical Cortical Brain Changes Associated with Chronic Low Back Pain

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The role of spinal cord extrasynaptic α 5 GABA A receptors in chronic pain

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 57 publications

Cys-loop receptors on cannabinoids: All high?

Cys-loop receptors on cannabinoids: All high?

Activation of α6-containing GABAA receptors induces antinociception under physiological and pathological conditions

Structural, Functional and Neurochemical Cortical Brain Changes Associated with Chronic Low Back Pain

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Product

Resources

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The role of spinal cord extrasynaptic α ₅ GABA _A receptors in chronic pain