µ1-Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post-ictal antinociception

• Published in: Synapse (New York, N.Y.) Vol. 70; no. 12; pp. 519 - 530
• Main Authors: de Freitas, Renato Leonardo, Medeiros, Priscila, Khan, Asmat Ullah, Coimbra, Norberto Cysne
• Format: Journal Article
• Language: English
• Published: Hoboken Blackwell Publishing Ltd 01-12-2016; Wiley Subscription Services, Inc
• Subjects: dorsomedial and ventrolateral columns of PAG; endogenous opioid peptides; GABAergic neurotransmission; post-ictal antinociception; tonic-clonic seizures; µ1-opioid receptors
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.21926

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.
Pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic–clonic seizures and post‐ictal antinociception. Microinjections of the µ1‐opioid receptor‐selective antagonist naloxonazine (5.0 µg/0.2 µL) in both the dmPAG and vlPAG decreased post‐ictal antinociception. These findings indicate that PAG µ1‐opioid receptor signalling mechanisms are involved in the organisation of post‐ictal antinociception.