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.