Neurotoxicity of Tramadol

tramadol is a centrally acting opioid analgesic with a dual mode of action. The most serious and significant adverse effects of tramadol are those of the central nervous system including dizziness, headache, seizures manifested as generalized seizures especially in young abusers with longer duration of tramadol abuse.The aim of this work was to study the neurotoxic effect of tramadol clinically& experimentally. This study was done in emergency departement, ICU, Toxicology unit and neurology departement in Zagazig university hospital. The clinical design included 60 patients. They were equally divided into 2 groups: group I (tramadol alone) and group II ( control group).They were all chosen according to inclusion and exclusion criteria.All patients were subjected to history taking, physical & neurological examination. The experimental design included fourty male albino rats weighting 180-220g. Rats were divided into control groups and gradual increasing doses group received tramadol at doses of 20,30&40 mg /kg/day on the first, second and third ten days of the study respectivelly intraperitoneally.Rats’ brains were removed and subjected to histopathological study. In tramadol abuse alone group, physical and neurological examination revealed that of the 30 patients included , (40%) had headache, (60%) had dizziness and (76.7%) had seizures. (78.3%) of them experienced seizures within 24 hrs after tramadol intake while (21.7%) had seizures after 24hrs of tramadol abuse. About (65.2%) patients had generalized seizures while (34.8%) had focal seizures. At doses <500 mg/day; (33.3%) had seizures while at larger doses about 77.7%-87.5.% had seizures.Of patients abused tramadol for a period ranged from 1-3 yrs (63.6%) had seizures while about 83-85.7% had seizures after abusing tramadol for more than 3 yrs. Experimental results revealed large amount of apoptotic neurons with pyknotic nuclei and many glial cells. The most common neurotoxic manifestations of tramadol abuse are headache, Dizziness and seizures.Seizures induced by tramadol abuse alone are dose and duration dependent, usually of generalized type and occur within 24hrs of ingestion.Histopathological changes in rats’ brains due to use of tramadol revealed increased apoptotic neurons and glial cells in the hippocampal areas of the brain.