Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception

Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0 μg/0.2 μL) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0 min) and subsequently at 10-min intervals until 130 min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130 min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity. [Display omitted] •The GABAA-receptor Cl− influx ionophore blockade causes tonic-clonic seizures.•Tonic-clonic seizures are followed by postictal hypoalgesia.•Ibotenic acid-induced PPTN lesions did not reduce the PTZ-induced seizure duration and severity.•PPTN neurotoxic lesions diminished the postictal antinociception.•Postictal antinociception depends on the PPTN neuronal cells integrity.