This study investigated the intrinsic connections of a key‐structure of the endogenous pain inhibitory system, the pedunculopontine tegmental nucleus (PPTN), in post‐ictal antinociceptive process through synaptic inactivation of the PPTN with cobalt chloride. Male Wistar rats (n = 6 or 7 per group), weighing 250–280 g, had the tail‐flick baseline recorded and were submitted to a stereotaxic surgery for the introduction of a guide‐cannula aiming at the PPTN. After 5 days of postoperative recovery, cobalt chloride (1 mM/0.2 µL) or physiological saline (0.2 µL) were microinjected into the PPTN and after 5 min, the tail‐withdrawal latency was measured again at 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 min after seizures evoked by intraperitoneal injection of pentylenetetrazole (64 mg/kg). The synaptic inactivation of PPTN decreased the post‐ictal antinociceptive phenomenon, suggesting the involvement of PPTN intrinsic connections in the modulation of pain, during tonic‐clonic seizures. These results showed that the PPTN may be crucially involved in the neural network that organizes the post‐ictal analgesia. Synapse 68:369–377, 2014. © 2014 Wiley Periodicals, Inc.