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CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain.

Abstract：

:Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1 cannabinoid receptor in in vitro functional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1 antagonist/inverse agonist AM251, but not by the CB2 antagonist AM630. In contrast, in post-operative pain model and phase I of formalin test, intracerebroventricular administration of mouse VD-Hpα induced dose-related analgesia in mice, which were markedly reduced by pretreatment with the CB1 neutral antagonist AM4113, but not AM251, AM630 and the selective antagonists of opioid and Transient Receptor Potential Vanilloid Type 1 (TRPV1) receptors. Furthermore, in the acetic acid-induced visceral pain model, supraspinal administration of mouse VD-Hpα dose-dependently produced analgesic activities and the effects were significantly antagonized by both AM4113 and the TRPV1 receptor antagonist SB366791, but not AM251, AM630 and naloxone. In addition, central injection of mouse VD-Hpα did not have significant effect in phase II of formalin test. Taken together, the present work suggests that the CB1 receptor peptidic agonist mouse VD-Hpα produces supraspinal analgesia in preclinical pain models via a novel CB1 receptor-mediated mechanism, in a manner pharmacologically dissociable from WIN 55,212-2. In addition, TRPV1 receptor might also be involved in mouse VD-Hpα-induced analgesia in a visceral pain model.

journal_name

Brain Res

journal_title

Brain research

authors

Zheng T,Zhang R,Zhang T,Zhang MN,Xu B,Song JJ,Li N,Tang HH,Wang P,Wang R,Fang Q

doi

10.1016/j.brainres.2017.12.013

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

155-164

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(17)30547-4

journal_volume

1680

pub_type

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CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain.