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

Rodríguez‐Palma, Erick J.; Luz-Cuellar, Yarim Elideth De la; Islas-Espinoza, Ana M.; Félix-Leyva, Adalberto E.; Shiers, Stephanie; García, Guadalupe; Torres-López, Jorge Elías; Delgado‐Lezama, Rodolfo; Murbartián, Janet; Price, Theodore J.; Granados‐Soto, Vinicio

doi:10.1097/j.pain.0000000000002763

Cited by 5 publications

(1 citation statement)

References 80 publications

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“…Numerous differences in pain mechanisms in males vs. females have emerged over recent years ( 10 ). For example loss of GABA A receptors containing the α6 subunit plays a predominant role in female rodents ( 557 ). The relative importance of CGRP in females ( 323 ), the role of macrophage derived IL-23 ( 368 ), and the absence of functional P2X receptors on microglia of female rodents have already been alluded to ( 364 ).…”

Section: Improved Basic Science Approachesmentioning

confidence: 99%

Neuropathic pain; what we know and what we should do about it

Smith

2023

Front. Pain Res.

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Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve injury promotes Schwann cell activation and invasion of immunocompetent cells into the site of injury, spinal cord and higher sensory structures such as thalamus and cingulate and sensory cortices. Various cytokines, chemokines, growth factors, monoamines and neuropeptides effect two-way signalling between neurons, glia and immune cells. This promotes sustained hyperexcitability and spontaneous activity in primary afferents that is crucial for onset and persistence of pain as well as misprocessing of sensory information in the spinal cord and supraspinal structures. Much of the current understanding of pain aetiology and identification of drug targets derives from studies of the consequences of peripheral nerve injury in rodent models. Although a vast amount of information has been forthcoming, the translation of this information into the clinical arena has been minimal. Few, if any, major therapeutic approaches have appeared since the mid 1990's. This may reflect failure to recognise differences in pain processing in males vs. females, differences in cellular responses to different types of injury and differences in pain processing in humans vs. animals. Basic science and clinical approaches which seek to bridge this knowledge gap include better assessment of pain in animal models, use of pain models which better emulate human disease, and stratification of human pain phenotypes according to quantitative assessment of signs and symptoms of disease. This can lead to more personalized and effective treatments for individual patients. Significance statement: There is an urgent need to find new treatments for neuropathic pain. Although classical animal models have revealed essential features of pain aetiology such as peripheral and central sensitization and some of the molecular and cellular mechanisms involved, they do not adequately model the multiplicity of disease states or injuries that may bring forth neuropathic pain in the clinic. This review seeks to integrate information from the multiplicity of disciplines that seek to understand neuropathic pain; including immunology, cell biology, electrophysiology and biophysics, anatomy, cell biology, neurology, molecular biology, pharmacology and behavioral science. Beyond this, it underlines ongoing refinements in basic science and clinical practice that will engender improved approaches to pain management.

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