Acetylcholine-mediated neurotransmission within the nucleus raphe magnus exerts a key role in the organization of both interictal and postictal antinociception

The role of the acetylcholine-mediated system in the organization of postictal antinociception was investigated. For this purpose, nicotinic and muscarinic cholinergic receptor antagonists were microinjected into the nucleus raphe magnus (NRM), a key structure of the endogenous pain inhibitory system. After the tail-flick test baseline recording, male Wistar rats (N=8 per group) were submitted to stereotaxic surgery for the introduction of a guide cannula aiming at the NRM. Five days after surgery, atropine or mecamylamine (1 µg/0.2 µL, 3 µg/0.2 µL, or 5 µg/0.2 µL) was microinjected into the NRM. The tail-flick withdrawal latency was recorded immediately after peripheral treatment with pentylenetetrazole (PTZ) (64 mg/kg), in two different interictal time windows, and for 130 minutes after the last seizure evoked by intraperitoneal injection of PTZ. The blockade of GABA-mediated Cl(-) influx caused tonic-clonic convulsions in all animals followed by sustained postictal antinociception lasting 110 minutes after seizures; the nociceptive threshold was also found to be high in interictal periods. Pretreatment of the NRM with either atropine or mecamylamine antagonized both interictal and postictal antinociception, suggesting the involvement of cholinergic mechanisms recruiting muscarinic and nicotinic cholinergic receptors of the NRM in the organization of tonic-clonic seizure-induced antinociception.