Loading…
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...
Saved in:
Published in: | Frontiers in pharmacology 2022, Vol.13, p.1023611 |
---|---|
Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
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 |