Antinociceptive effect of Lonchocarpus araripensis lectin: activation of L-arginine/NO/cGMP/K ⁺ ATP signaling pathway

Objective and design: The involvement of nitric oxide pathway in the antinociceptive activity of Lonchocarpus araripensis lectin (LAL) was investigated in the model of carragenan-induced hypernociception.

Methods: Swiss mice received LAL (0.01-10 mg/kg; i.v.) 30 min before s.c. injection of carragenan in the paws. For the involvement of nociceptive pathways, animals were previously treated with the blockers: NOS (L-NAME, aminoguanidine, 7-nitroindazole); soluble guanylyl cyclase (ODQ); channels of ATP-dependent K⁺ (glibenclamide); L-type Ca²⁺ (nifedipine), or Ca²⁺-dependent Cl^- (niflumic acid). Participation of lectin domain was evaluated by injection of LAL associated with N-acetyl-glucosamine (GlcNAc). nNOS gene relative expression was evaluated in the paw tissues and nNOS immunostaining in dorsal root ganglia.

Results: LAL at all doses inhibited carrageenan-induced hypernociception (4.12 ± 0.58 g), being maximal at 10 mg/kg (3 h: 59%), and reversed by GlcNAc. At this time, LAL effect was reversed by nifedipine (39%), niflumic acid (59%), L-NAME (59%), 7-nitroindazole (44%), ODQ (45%), and glibenclamide (34%), but was unaltered by aminoguanidine. LAL increased (95%) nNOS gene expression in mice paw tissues, but not its immunoexpression in the dorsal root ganglia.

Conclusion: The antinociceptive effect of Lonchocarpus araripensis lectin involves activation of the L-arginine/NO/GMPc/K⁺ATP pathway.

Keywords: Dalbergieae lectin; Hypernociception; Nitric oxide; nNOS.