Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation of ATP-sensitive K+ channels.

Aims: The effects of several potassium (K(+)) channel blockers were studied to determine which K(+) channels are involved in peripheral antinociception induced by the cannabinoid receptor agonist, anandamide.

Main Methods: Hyperalgesia was induced by subcutaneous injection of 250 μg carrageenan into the plantar surface of the hind paw of rats. The extent of hyperalgesia was measured using a paw pressure test 3 h following carrageenan injection.

Central antinociception induced by mu-opioid receptor agonist morphine, but not delta- or kappa-, is mediated by cannabinoid CB1 receptor.

Background And Purpose: It has been demonstrated that cannabinoids evoke the release of endogenous opioids to produce antinociception; however, no information exists regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids are involved in central antinociception induced by activation of mu-, delta- and kappa-opioid receptors.

Experimental Approach: Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice.

Opioid receptor and NO/cGMP pathway as a mechanism of peripheral antinociceptive action of the cannabinoid receptor agonist anandamide.

Aims: In this study, we investigated whether the opioid system and the nitric oxide pathway were involved in the peripheral antinociception induced by a cannabinoid receptor agonist anandamide.

Main Methods: Hyperalgesia was induced by a subcutaneous injection of carrageenan (250 microg) into the plantar surface of the rat's hindpaw and measured by the paw pressure test 3h after injection. The weight in grams (g) required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold.

Involvement of chloride channel coupled GABA(C) receptors in the peripheral antinociceptive effect induced by GABA(C) receptor agonist cis-4-aminocrotonic acid.

We investigated the effect of chloride and potassium channel blockers on the antinociception induced by GABA(C) receptor agonist CACA (cis-4-aminocrotonic acid) using the paw pressure test, in which pain sensitivity was increased by an intraplantar injection (2 microg) of prostaglandin E(2) (PGE(2)). CACA administered locally into the right hindpaw (25, 50 and 100 microg/paw) elicited a dose-dependent antinociceptive effect which was demonstrated to be local, since only higher doses produced an effect when injected in the contralateral paw. The GABA(C) receptor antagonist (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA; 5, 10 and 20 microg/paw) antagonized, in a dose-dependent manner, the peripheral antinociception induced by CACA (100 microg), suggesting a specific effect.

delta-Opioid receptor agonist SNC80 elicits peripheral antinociception via delta(1) and delta(2) receptors and activation of the l-arginine/nitric oxide/cyclic GMP pathway.

In this study, we characterized the role of delta(1) and delta(2) opioids receptors, as well the involvement of the l-arginine/NO/cGMP pathway in the peripheral antinociception induced by delta-opioid receptor agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). The paw pressure test was utilized, in which pain sensitivity is increased by intraplantar injection of prostaglandin E(2) (2 microg). Administration of SNC80 (20, 40 and 80 microg/paw) decreased the hyperalgesia induced by prostaglandin E(2) in a dose-dependent manner.