title: Modulation of peripheral inflammatory pain thresholds by M(1) and nicotinic receptor antagonists.
abstract: The study used the paw withdrawal test to investigate the role of the cholinergic system on the modulation of inflammatory pain induced by carrageenan (Cg) at the peripheral level, through activation of muscarinic and nicotinic receptors. Intraplantar administration of the specific M(1) receptor antagonist telenzepine (TEL; 6, 12 and 24 μg/paw) caused a dose-dependent reduction in the nociceptive threshold induced by Cg (125 μg/paw). This effect was not observed with increasing doses (4, 10 and 40 μg) of other specific receptor antagonists: M(2) (dimethindene), M(3) (4-DAMP) and M(4) (tropicamide). The nicotinic antagonist mecamylamine (MEC; 25, 50 and 100 μg/paw) also caused a dose-dependent reduction in the nociceptive threshold induced by Cg (125 μg). To exclude a non-local effect, Cg (125 μg) was injected into both hind paws, while TEL (12 μg) and MEC (50 μg) were administered only in the right paw. At these doses, the muscarinic antagonists increased inflammatory pain only in the treated right paw, suggesting a peripheral effect. In the presence of prostaglandin E(2) (1 μg/paw), TEL (12 μg) and MEC (50 μg) did not reduce the nociceptive threshold, suggesting that this hyperalgesic agent does not induce the release of endogenous acetylcholine. These data suggest that muscarinic M(1) and nicotinic receptors participate in the modulation of endogenous cholinergic inflammatory pain at the peripheral level.
authors: Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.
authors: Patrícia G
authors: PG
authors: Motta
authors: Andrea C
authors: AC
authors: Perez
authors: Daniela P
authors: DP
authors: Alves
authors: Igor D G
authors: ID
authors: Duarte
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan; D015232:Dinoprostone; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors*
chemical_list: D018733:Nicotinic Antagonists; D043643:Receptor, Muscarinic M1; C046338:telenzepine; D010890:Pirenzepine; D008464:Mecamylamine; D002351:Carrageenan; D015232:Dinoprostone; D000109:Acetylcholine