Central analgesic effect of valproate in patients with epilepsy

Clinical practitioners have often observed in the course of their daily work that the pain thresholds of epileptic patients seem to differ from those of healthy subjects. These patients can suffer from quite severe traumatic lesions without apparently experiencing any pain. Previous studies have shown that the absence of pain is due to treatment, since most antiepileptic drugs also have analgesic effects. In the present study, it was proposed to assess the pain thresholds of 15 epileptic patients (with tonic-clonic seizures generalized at outset) treated with valproate, by measuring the leg flexion nociceptive reflex (or RIII reflex) threshold: the stimulation threshold at which this reflex is triggered is known to be correlated with the pain threshold. The results were compared with 15 control subjects. The nociceptive threshold of the patients with valproate treatment was significantly higher than that of the control population. The nociceptive threshold was also in good correlation with the valproate plasma level. These data are discussed from the point of view of the gaba-ergic system and mechanisms possibly involved.