P19: The toxic effect of prolonged Ultram administration on cerebral cortex of albino rats: Toxicological and histological study

Abstract

Ultram (Tramadol) is a widely used opioid analgesic effective in treating both acute and chronic pains and has acceptable adverse effects such as headache, nausea constipation and vertigo. The aim of the present study was to evaluate the cerebrocortical toxicity resulting from short term and long term Ultram administration to albino rats using biochemical and histological parameters. The study was carried out on 25 adult male albino rats divided into: control group received 0.5 ml/day saline orally by orogastric tube for 2 months, a short-term Ultram-treated group that received a dose of 30 mg/kg/day (1/10 LD50) for 1 month orally and a long-term Ultram–treated group that received the same dose for 2 months. The study revealed that Ultram administration caused a significant elevation of serotonin level in the cerebral cortical tissues of rats which was directly proportional to the duration of Ultram administration. Histologically, there were localized foci showing disorganization of the cortical layers in short term ultram treated group. While in long-term Ultram–treated one there were much disorganization of the cortical layers with vacuolated foci and cell loss. Ultrastructurally the neurons in the different layers of cerebral cortex associated with degenerative changes and damage of rough endoplasmic reticulum in the form of chromatolysis and degranulation which were more evident with the 2 months Ultram dosing than with 1 month. The correlation between the biochemical results and the histological findings proved that Ultram induced neuronal lesions could be mediated by the elevated cerebrocortical serotonin level which gives serious alarms for reconsidering the rush towards the excessive use of Ultram.