Peripheral antinociceptive effect of exogenous acetylcholine seems to be mediated by M1 and nicotinic receptors

The purpose of this study is to identify the cholinergic receptor subtype that mediates the peripheral antinociceptive effect of acetylcholine. To induce hyperalgesia, rat paws were treated with intraplantar prostaglandin E 2 (PGE 2 , 2 μ g). The nociceptive thresholds to pressure (grams) were measured by paw flexion reaction using an algesimeter apparatus 3 h following injection. Intraplantar administration of acetylcholine (ACh; 50, 100, 200 and 400 μ g) caused dose-dependent antinociception in PGE 2 induced hyperalgesia. The subtype-selective muscarinic receptor antagonists for M 1 (telenzepine; 3, 6 and 12 μ g), M 2 (dimethindene; 40 and 80 μ g), M 3 (4-DAMP, 40 and 80 μ g), and M 4 (tropicamide; 40 and 80 μ g) as well as the nicotinic antagonist (mecamylamine; 25, 50 and 100 μ g) were all co-administered with acetylcholine (200 μ g). Only telenzepine and mecamylamine antagonized the antinociceptive effect of ACh. These data suggest the presence of M 1 and nicotinic cholinergic receptors at the peripheral level and that exogenous acetylcholine induces receptor activation with consequent antinociception.