Role of muscarinic and nicotinic cholinergic receptors in an experimental model of epilepsy-induced analgesia.
The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used in the present work to induce seizures in animals. The neurotransmission in the postictal period has been the focus of many studies, and there is evidence suggesting antinociceptive mechanisms following tonic-clonic seizures in both animals and men. The aim of this work was to study the involvement of acetylcholine in the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). Analgesia was measured by the tail-flick test in eight albino Wistar rats per group. Convulsions were followed by significant increases in tail-flick latencies (TFLs) at least for 120 min of the postictal period. Peripheral administration of atropine (0.25, 1 and 4 mg/kg) caused a significant dose-dependent decrease in the TFL in seizing animals, as compared to controls. These data were corroborated by peripheral administration of mecamylamine, a nicotinic cholinergic receptor blocker, at the same doses (0.25, 1 and 4 mg/kg) used for the muscarinic cholinergic receptor antagonist. The recruitment of the muscarinic receptor was made 10 min postconvulsions and in subsequent periods of postictal analgesia, whereas the involvement of the nicotinic cholinergic receptor was implicated only after 30 min postseizures. The cholinergic antagonists caused a minimal reduction in body temperature, but did not impair baseline TFL, spontaneous exploration or motor coordination in the rotarod test at the maximal dose of 4 mg/kg. These results indicate that acetylcholine may be involved as a neurotransmitter in postictal analgesia.
de Freitas
Renato Leonardo
RL
Laboratório de Neuroanatomia e Neuropsicobiologia, Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), 14049-900, Avenida dos Bandeirantes, 3900, Ribeirão Preto (SP), Brazil.
de Oliveira
Rithiele Cristina
RC
de Carvalho
Andressa Daiane
AD
Felippotti
Tatiana Tocchini
TT
Bassi
Gabriel Shimizu
GS
Elias-Filho
Daoud Hibrahim
DH
Coimbra
Norberto Cysne
NC
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018756:GABA Antagonists / Q000633:toxicity; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000503:physiopathology*; D010147:Pain Measurement; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*
D002712:Chlorides; D003292:Convulsants; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D001285:Atropine; D010433:Pentylenetetrazole