Involvement of the NO/cGMP/PKG/KATP pathway and endogenous opioids in the antinociceptive effect of a sulphated-polysaccharide fraction extracted from the red algae, Gracilaria caudata

We investigated the antinociceptive activity of a sulphated-polysaccharide (PLS) fraction extracted from the sea algae Gracilaria caudata against carrageenan-induced hypernociception in mice and the mechanism underlying the antinociceptive activity. Mechanical inflammatory hypernociception was measured with an electronic version of the Von Frey® test. Mice were treated with PLS (2.5, 5.0, and 10 mg/kg, 0.5 mL, p.o.) 1 h before carrageenan treatment. l-Noarg (100 ng/paw; 50 μL) was administered 1 h before carrageenan administration. l-Arg (l-Arginine; 200 mg/kg; 0.5 mL, p.o.) was administered 10 min before l-Noarg injection. ODQ (8 μg/paw), KT 5823 (1.5 μg/paw), glibenclamide (160 μg/paw), and naloxone (1.0 μg/paw) were administered 30 min before carrageenan administration. PLS reduced carrageenan-induced hypernociception (300 μg/paw, 50 μL, intraplantar injection). PLS-induced analgesia was reversed by l-Noarg, and the effect of l-Noarg was prevented by l-Arg. The soluble guanylyl cyclase inhibitor ODQ, the protein kinase G inhibitor KT 5823, the KATP blocker glibenclamide, and the opioid receptor antagonist naloxone, significantly reversed (P < 0.05) the antinociceptive effect of PLS. The present study showed an intrinsic peripheral antinociceptive action of PLS administration in mice. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP/PKG pathway followed by the opening of KATP channels, and depended on endogenous opioids.