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The differential in vivo contribution of spinal α2A- and α2C-adrenoceptors in tonic and acute evoked nociception in the rat
Spinal α 2 -adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G i/o proteins can be subdivided into three functional subtypes: α 2A , α 2B, and α 2C -adrenoceptors, and current evidence on spinal analgesia supports the relevance of α 2A...
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Published in: | Frontiers in pharmacology 2022-11, Vol.13, p.1023611-1023611 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | Spinal α
2
-adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G
i/o
proteins can be subdivided into three functional subtypes: α
2A
, α
2B,
and α
2C
-adrenoceptors, and current evidence on spinal analgesia supports the relevance of α
2A
and seems to exclude the role of α
2B
, but the functional contribution of α
2C
-adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal α
2
-adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective α
2A/
α
2B/
α
2C
-adrenoceptor agonist) and/or selective subtype α
2
-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 (α
2A
-adrenoceptor antagonist) but not by imiloxan (α
2B
-adrenoceptor antagonist) or JP 1302 (α
2C
-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 GABA
A
channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic α
2A
-adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal α
2C
-adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of α
2A
and α
2C
-adrenoceptors modulating nociception. |
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ISSN: | 1663-9812 1663-9812 |
DOI: | 10.3389/fphar.2022.1023611 |