Investigation into atropine‐induced antinociception

1 The effect of atropine on the nociceptive system was examined in mice and rats by use of the hot‐plate, writhing and tail‐flick tests. 2 Atropine dose‐dependently produced analgesia, no effect and hyperalgesia. Analgesia was observed in both species with doses ranging from 1 to 100 μg kg−1 while hyperalgesia was obtained with 5 mg kg−1. 3 Atropine antinociception was prevented by pirenzepine (0.1 μg per mouse, i.c.v.), dicyclomine (10 mg kg−1, i.p.), atropine‐methylbromide (0.5 μg per mouse, i.c.v.) and hemicholinium‐3 (1 μg per mouse, i.c.v.). Naloxone (1 mg kg−1, i.p.), α‐methyl‐p‐tyrosine (100 mg kg−1, s.c.) and reserpine (2 mg kg−1, i.p.) were ineffective. 4 The site of atropine analgesia is in the CNS since it exerts its antinociceptive effect also when injected i.c.v. (1–10 ng per mouse). Moreover drugs which do not cross the blood‐brain barrier, such as hemicholinium‐3, pirenzepine and atropine methylbromide, were unable to antagonize atropine analgesia if administered i.p. 5 Atropine also in vitro, showed a biphasic action on electrically‐evoked guinea‐pig ileum contractions. Concentrations between 10−14 and 10−12m increased electrically and nicotine‐evoked contractions but did not affect acetylcholine‐ and oxotremorine‐evoked contractions. Concentrations above 10−9m inhibited both electrically‐ and drug (acetylcholine, nicotine and oxotremorine)‐evoked contractions while they were ineffective on unstimulated ileum. 6 On the basis of the above findings, amplification of cholinergic transmission by very low doses of atropine is postulated, through a selective blockade of presynaptic muscarinic autoreceptors, as the likely mechanism of action. 7 Atropine antinociception, unlike oxotremorine antinociception, was obtained without any impairment of mouse rota‐rod performance. 8 The antagonism by pirenzepine and dicyclomine of oxotremorine and atropine antinociception suggests that M1 muscarinic receptor subtypes are responsible for cholinergic analgesia.