The differential in vivo contribution of spinal a2A- and a2C-adrenoceptors in tonic and acute evoked nociception in the rat
Por:
Lopez-Cordoba, Gustavo, Martinez-Lorenzana, Guadalupe, Lozano-Cuenca, Jair, Condes-Lara, Miguel, Gonzalez-Hernandez, Abimael
Publicada:
1 ene 2022
Resumen:
Spinal a2-adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to Gi/o proteins can be subdivided into three functional subtypes: a2A, a2B, and a2C-adrenoceptors, and current evidence on spinal analgesia supports the relevance of a2A and seems to exclude the role of a2B, but the functional contribution of a2C-adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal a2-adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective a2A/a2B/a2C-adrenoceptor agonist) and/or selective subtype a2-adrenoceptor antagonists on: 1) tonic nociception induced by subcutaneous formalin (flinching behavior) or 2) acute nociception induced by peripheral electrical stimulus in in vivo extracellular recordings of spinal dorsal horn second-order wide dynamic range (WDR) neurons. Clonidine inhibited the nocifensive behavior induced by formalin, an effect blocked by BRL 44408 (a2A-adrenoceptor antagonist) but not by imiloxan (a2B-adrenoceptor antagonist) or JP 1302 (a2C-adrenoceptor antagonist). Similarly, spinal BRL 44408 reversed the clonidine-induced inhibition of nociceptive WDR activity. Interestingly, spinal JP 1302 per se produced behavioral antinociception (an effect blocked by bicuculline, a preferent GABAA channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic a2A-adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal a2C-adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of a2A and a2C-adrenoceptors modulating nociception. Copyright © 2022 López-Córdoba, Martínez-Lorenzana, Lozano-Cuenca, Condés-Lara and González-Hernández.
Filiaciones:
Lopez-Cordoba, Gustavo:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
Martinez-Lorenzana, Guadalupe:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
Lozano-Cuenca, Jair:
Departamento de Biología Celular, Secretaría de Salud, Instituto Nacional de Perinatología, Mexico City, Mexico
Condes-Lara, Miguel:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
Gonzalez-Hernandez, Abimael:
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, Mexico
Green Published, gold, All Open Access; Gold
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