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 µ -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 µ -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 µ -opioid receptor-signalling mechanisms in both dmPAG and vlPAG play a relevant role in the organisation of post-ictal antinociception. In addition, µ -opioid receptors in the dmPAG rather than in vlPAG seem to be more critically recruited during the antinociception induced by generalised tonic-clonic seizures.

Distribution of alpha‐neoendorphin, ACTH (18–39) and beta‐endorphin (1–27) in the alpaca brainstem

“…Here, we have reported a moderate/low density of immunoreactive fibres containing beta‐endorphin (1–27) in the area postrema, locus coeruleus, reticular formation, nucleus of the solitary tract, dorsal nucleus of the raphe and the periaqueductal gray. This means that the peptide could be involved in the control of pain transmission, sleep–waking cycle, taste, feeding, respiratory, cardiovascular, vigilance and stress mechanisms (Cerritelli, Hirschberg, Hill, Balthasar, & Pickering, ; de Freitas, Medeiros, & Khan, ; Li et al., ; Lima, Leite, Bethea, & Anselmo‐Franci, ).…”

Modelos neuropsicobiológicos para estudo da dor e das emoções

“…garantido as boas práticas éticas em experimentação animal. De fato, caso o animal não retire a cauda, o experimento é interrompido para não correr o risco de lesões (Freitas et al, 2014a(Freitas et al, , 2014bFreitas et al, 2016) (Figura 1D).…”

GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation

“…Intraperitoneal (ip) injections of the noncompetitive GABA A receptor antagonist pentylenetetrazole (PTZ) induce tonic‒clonic seizures in laboratory animals The convulsive effect of PTZ is due to GABA-mediated Cl - influx blockade. In addition, although pain sensitivity after PTZ varies according to the age of laboratory animals 1 , seizures caused by PTZ in young adult rodents are followed by significant antinociception 2 , 3 , a postictal and interictal phenomenon that recruits endogenous opioids 4 – 8 , norepinephrine 2 , 9 , serotonin 2 , 7 , 10 – 13 , and acetylcholine 14 – 19 . Indeed, neurochemical lesions of brainstem nuclei rich in indolamines 2 , such as the dorsal raphe nucleus; in norepinephrine 2 , such as the locus coeruleus; and in acetylcholine 19 , such as the pedunculopontine tegmental nucleus, impair the postictal antinociception that follows acute tonic‒clonic seizures caused by a single intraperitoneal injection of PTZ.…”