title: µ1-Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post-ictal antinociception.
abstract: Generalised tonic and tonic-clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ1-opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA-mediated Cl-influx antagonist, was intraperitoneally (IP) administered to induce tonic-clonic seizures in Wistar rats. The tail-flick test was used to measure the nociceptive threshold. Microinjections of naltrexone (5.0 µg/0.2 µL), which is a non-selective opioid receptor antagonist, in both dmPAG and vlPAG decreased the tonic-clonic seizure-induced antinociception in seizing animals from 10 to 120 min after seizures. Furthermore, microinjections of the µ1-opioid receptor-selective antagonist naloxonazine (5.0 µg/0.2 µL) into the dmPAG decreased post-ictal antinociception immediately after convulsive reactions and from 10 to 90 min after seizures. However, vlPAG-pretreatment with naloxonazine at the same concentration decreased the post-ictal antinociception 30 min after the onset of tonic-clonic seizures and the nociceptive threshold returned to basal values 120 min after seizures. These findings indicate that µ1-opioid receptor-signalling mechanisms in both dmPAG and vlPAG play a relevant role in the organisation of post-ictal antinociception. In addition, µ1-opioid receptors in the dmPAG rather than in vlPAG seem to be more critically recruited during the antinociception induced by generalised tonic-clonic seizures.
authors: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.|Department of Surgery and Anatomy, Multiuser Centre of Neurophysiology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.|Laboratory of Pain and Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.|Behavioural Neurosciences Institute, Av. do Café, 2450, Ribeirão Preto, São Paulo, 14050-220, Brazil.
authors: Renato Leonardo
authors: RL
authors: de Freitas
authors: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.|Laboratory of Pain and Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors: Priscila
authors: P
authors: Medeiros
authors: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.|Department of Eastern Medicine and Surgery, School of Medical and Health Sciences of the University of Poonch Rawalakot, Azad Jammu and Kashmir, Pakistan.
authors: Asmat Ullah
authors: AU
authors: Khan
authors: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil. nccoimbr@fmrp.usp.br.|Laboratory of Pain and Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil. nccoimbr@fmrp.usp.br.|Behavioural Neurosciences Institute, Av. do Café, 2450, Ribeirão Preto, São Paulo, 14050-220, Brazil. nccoimbr@fmrp.usp.br.
authors: Norberto Cysne
authors: NC
authors: Coimbra
mesh_terms: D000818:Animals; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D059225:Nociception; D017288:Pain Threshold; D010433:Pentylenetetrazole / Q000633:toxicity; D010487:Periaqueductal Gray / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000503:physiopathology
chemical_list: D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; C034643:naloxonazine; D010433:Pentylenetetrazole
keywords: GABAergic neurotransmission; dorsomedial and ventrolateral columns of PAG; endogenous opioid peptides; post-ictal antinociception; tonic-clonic seizures; µ1-opioid receptors