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 E2 (PGE2, 2 μg). 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 μg) caused dose-dependent antinociception in PGE2-induced hyperalgesia. The subtype-selective muscarinic receptor antagonists for M1 (telenzepine; 3, 6 and 12 μg), M2 (dimethindene; 40 and 80 μg), M3 (4-DAMP, 40 and 80 μg), and M4 (tropicamide; 40 and 80 μg) as well as the nicotinic antagonist (mecamylamine; 25, 50 and 100 μg) were all co-administered with acetylcholine (200 μg). Only telenzepine and mecamylamine antagonized the antinociceptive effect of ACh. These data suggest the presence of M1 and nicotinic cholinergic receptors at the peripheral level and that exogenous acetylcholine induces receptor activation with consequent antinociception.
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