Antinociceptive effects of bethanechol or dimethylphenylpiperazinium in models of phasic or incisional pain in rats.
The mechanism by which muscarinic or nicotinic agonists produce antinociception has been the subject of several studies. In the present investigation, we used intrathecal administration of drugs to rats to show that muscarinic or nicotinic agonists such as bethanechol (BCh) and dimethylphenylpiperazinium (DM), respectively, dose-dependently increased the tail flick latency and reduced the pain produced by a surgical incision performed on the plantar aspect of a hind paw. The effects of BCh in both tests were inhibited by the previous intrathecal administration of atropine, but not mecamylamine (muscarinic and nicotinic antagonists, respectively). Mecamylamine significantly reduced the effects of DM in both tests. Atropine significantly reduced the effect of DM in the tail flick test and inhibited the effect of DM against the incisional pain. Intrathecal hemicholinium-3 (HC-3), a reversible inhibitor of choline transporter, did not change the effect of BCh in the tail flick test but produced a non-significant reduction of the effect of BCh against incisional pain. In contrast, HC-3 produced a non-significant reduction of the effect of DM in the tail flick test but fully inhibited the effect of DM against incisional pain. Therefore, the BCh-induced antinociception depends on a direct activation of muscarinic receptors, whereas DM-induced antinociception results in drug interaction with nicotinic receptors to activate the further release of acetylcholine from intrinsic spinal cholinergic terminals. The acetylcholine released by DM in turn induces antinociception via activation of muscarinic receptors.
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP, Brazil. wadprado@fmrp.usp.br
Wiliam A
WA
Prado
Daniel K
DK
Segalla
D000109:Acetylcholine / Q000502:physiology; D000700:Analgesics / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol / Q000008:administration & dosage*; D018679:Cholinergic Agonists / Q000008:administration & dosage*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006426:Hemicholinium 3 / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D015999:Multivariate Analysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D014947:Wounds and Injuries / Q000150:complications
D000700:Analgesics; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D018723:Bethanechol; D006426:Hemicholinium 3; D004246:Dimethylphenylpiperazinium Iodide; D008464:Mecamylamine; D001285:Atropine; D000109:Acetylcholine