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The differential in vivo contribution of spinal α 2A - and α 2C -adrenoceptors in tonic and acute evoked nociception in the rat

Spinal α -adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G proteins can be subdivided into three functional subtypes: α , α and α -adrenoceptors, and current evidence on spinal analgesia supports the relevance of α and seems to exclu...

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Bibliographic Details
Published in:Frontiers in pharmacology 2022, Vol.13, p.1023611
Main Authors: López-Córdoba, Gustavo, Martínez-Lorenzana, Guadalupe, Lozano-Cuenca, Jair, Condés-Lara, Miguel, González-Hernández, Abimael
Format: Article
Language:English
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Summary:Spinal α -adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G proteins can be subdivided into three functional subtypes: α , α and α -adrenoceptors, and current evidence on spinal analgesia supports the relevance of α and seems to exclude the role of α , but the functional contribution of α -adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal α -adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective α α α -adrenoceptor agonist) and/or selective subtype α -adrenoceptor antagonists on: 1) tonic nociception induced by subcutaneous formalin (flinching behavior) or 2) acute nociception induced by peripheral electrical stimulus in 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 (α -adrenoceptor antagonist) but not by imiloxan (α -adrenoceptor antagonist) or JP 1302 (α -adrenoceptor antagonist). Similarly, spinal BRL 44408 reversed the clonidine-induced inhibition of nociceptive WDR activity. Interestingly, spinal JP 1302 produced behavioral antinociception (an effect blocked by bicuculline, a preferent GABA channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic α -adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal α -adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of α and α -adrenoceptors modulating nociception.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.1023611