title: Dorsal raphe nucleus acetylcholine-mediated neurotransmission modulates post-ictal antinociception: The role of muscarinic and nicotinic cholinergic receptors.
abstract: The dorsal raphe nucleus (DRN) is a key structure of the endogenous pain inhibitory system. Although the DRN is rich in serotoninergic neurons, cholinergic neurons are also found in that nucleus. Both ictal and inter-ictal states are followed by post-ictal analgesia. The present study investigated the role of cholinergic mechanisms in postictal antinociceptive processes using microinjections of atropine and mecamylamine, muscarinic and nicotinic cholinergic receptor antagonists, respectively, in the DRN of rats. Intraperitoneal injection of pentylenetetrazole (PTZ) (at 64mg/kg) caused tonic and tonic-clonic seizures. The convulsive motor reactions were followed by an increase in pain thresholds, a phenomenon known as post-ictal analgesia. Pre-treatment of the DRN with atropine or mecamylamine at 1µg, 3µg and 5µg/0.2µL decreased the post-ictal antinociceptive phenomenon. The present results showed that the post-ictal analgesia was mediated by muscarinic and nicotinic cholinergic receptors in the DRN, a structure crucially involved in the neural network that organises post-ictal hypoalgesia.
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-900, Brazil.
authors.forename: Rithiele Cristina
authors.initials: RC
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-900, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-900, Brazil.
authors.forename: Audrey Francisco
authors.initials: AF
authors.lastname: Biagioni
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-900, Brazil.
authors.forename: Luiz Luciano
authors.initials: LL
authors.lastname: Falconi-Sobrinho
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, School of Medicine of Ribeirão Preto of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, SP 14040-900, Brazil. Electronic address: nccoimbr@fmrp.usp.br.
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000503:physiopathology*; D004830:Epilepsy, Tonic-Clonic / Q000378:metabolism / Q000503:physiopathology; D059330:GABAergic Neurons / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D059326:Serotonergic Neurons / Q000502:physiology; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000700:Analgesics; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D001285:Atropine; D000109:Acetylcholine
keywords: Dorsal raphe nucleus; Muscarinic cholinergic receptor; Nicotinic cholinergic receptor; Post-ictal antinociception; Tonic-clonic seizure