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Dexmedetomidine and ST-91 analgesia in the formalin model is mediated by alpha2A-adrenoceptors: a mechanism of action distinct from morphine.

Abstract：

BACKGROUND AND PURPOSE:Intrathecal administration of alpha(2)-adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal alpha(2)-adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST-91 in the formalin behavioural model and their effects on primary afferent substance P (SP) release and spinal Fos activation. EXPERIMENTAL APPROACH:The analgesic effects of i.t. dexmedetomidine and ST-91 (alpha(2) agonists) were tested on the formalin behavioural model. To determine the subtype of alpha(2)-adrenoceptor involved in the analgesia, i.t. BRL44408 (alpha(2A) antagonist) or ARC239 (alpha(2B/C) antagonist) were given before dexmedetomidine or ST-91. Moreover, the ability of dexmedetomidine and ST-91 to inhibit formalin-induced release of SP from primary afferent terminals was measured by the internalization of neurokinin(1) (NK(1)) receptors. Finally, the effects of dexmedetomidine on formalin-induced Fos expression were assessed in the dorsal horn. KEY RESULTS:Intrathecal administration of dexmedetomidine or ST-91 dose-dependently reduced the formalin-induced paw-flinching behaviour in rats. BRL44408 dose-dependently blocked, whereas ARC239 had no effect on the analgesic actions of dexmedetomidine and ST-91. Dexmedetomidine and ST-91 had no effect on the formalin-induced NK(1) receptor internalization, while morphine significantly reduced the NK(1) receptor internalization. On the other hand, both dexmedetomidine and morphine diminished the formalin-induced Fos activation. The effect of dexmedetomidine on formalin-induced Fos activation was reversed by BRL44408, but not ARC239. CONCLUSION AND IMPLICATIONS:These findings suggest that alpha(2A)-adrenoceptors mediate dexmedetomidine and ST-91 analgesia. This effect could be through a mechanism postsynaptic to primary afferent terminals, distinct from that of morphine.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Nazarian A,Christianson CA,Hua XY,Yaksh TL

doi

10.1038/bjp.2008.341

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

1117-26

issue

eissn

0007-1188

issn

1476-5381

pii

bjp2008341

journal_volume

155

pub_type

杂志文章

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Dexmedetomidine and ST-91 analgesia in the formalin model is mediated by alpha2A-adrenoceptors: a mechanism of action distinct from morphine.