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BioMed Research International
Volume 2014, Article ID 238780, 9 pages
Research Article

Biochemical and Neurotransmitters Changes Associated with Tramadol in Streptozotocin-Induced Diabetes in Rats

1Drug Bioavailability Laboratory, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2National Organization for Drug Control and Research, P.O. Box 29 Cairo, Egypt
3Pharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al Azhar University, Cairo, Egypt
4Pharmacognosy Department, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

Received 2 February 2014; Accepted 23 March 2014; Published 26 May 2014

Academic Editor: George Perry

Copyright © 2014 Essam Ezzeldin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed.