Abstracts

Rationale: Previous studies have demonstrated that patients with intractable temporal lobe epilepsy present enhanced mu-opioid and nociceptin receptor binding in the neocortex surrounding the epileptic focus, an area proposed to play an important role in the seizure expression and propagation. According with this group of evidence, it has been suggested an enhanced opioidergic transmission in the epileptic neocortex, a situation that may constrain the propagation of seizure activity to other brain areas. However, at the present it is unknown if the opioid receptor coupling efficiency is modified in the epileptic human neocortex. The main purpose of the present study was to evaluate the mu opioid and nociceptin receptor-activated G-protein binding in the temporal neocortex of patients with pharmacoresistant temporal lobe epilepsy. Methods: We used (35S)-guanylyl-5-o-(γ-thio)-triphosphate (GTPγS) binding which provides a measure of functional receptor activity. Temporal cortices were surgically obtained from epileptic patients with temporal lobe epilepsy associated with mesial sclerosis (n=11) or tumors (n=14). Correlations between (35S)GTPγS binding and clinical data were carried out. Autopsy material acquired from subjects without epilepsy (n=6) was used as control. Results: The neocortex from patients with temporal lobe epilepsy demonstrated reduced mu (64%) and nociceptin (65%)-stimulated (35S)GTPγS-binding, when compared with control tissue. No significant differences were detected between data obtained from patients with mesial sclerosis and tumors. A significant correlation was found between nociceptin-stimulated(35S)GTPγS-binding and epilepsy duration (r=0.5951, p<0.05) in patients with temporal lobe epilepsy with mesial sclerosis. Conclusions: In contrast with previous studies using Positron Emission Tomography and in vitro autoradiography, the present results support an impaired opioidergic transmission in the neocortex surrounding the epileptic focus of patients with pharmacoresistant temporal lobe epilepsy. This situation could be involved in the mechanisms of propagation of seizure activity to other brain areas. Study supported by CONACyT, Mexico (grants J110.342/2007, 45943-M) and Hungarian grants (TET 09/2005, ETT577/2006, RET67/2005, OTKA T46434).