Alterations in aminergic system of rat brain by the opioid analgesic tramadol in the absence of pain-induction

Background: Tramadol is an opioid analgesic used for treating moderate to severe pain. No research is available on pharmacology of tramadol without induction of pain. This study examines the effect of administration of tramadol on the levels of biogenic amines and their metabolites in the brain areas of male adult Wistar rats, without inducing pain.Methods: Tramadol was injected subcutaneously at 0, 24, and 48 hours, and changes in the levels of epinephrine (EP), norepinephrine (NE), dopamine (DA) and serotonin (5-HT), 5-hydroxyindoleacetic acid (HIAA) and homovanillic acid (HVA) were examined in cerebral cortex, cerebellum, pons-medulla, hippocampus and thalamus. The changes were recorded in the select brain areas at 3, 6, 12, 24 hours after the first injection, as well as at 24 hours after the second and third injections, respectively.Results: Administration of tramadol at 0 hours elevated the levels of DA, 5-HT and HVA in all brain areas. Changes in levels of EP, NE, and HIAA varied across the four brain areas surveyed. All parameters showed maximal changes at 3 or 6 hours following the first administration at 0 hours. For the second and third doses of tramadol at 24 and 48 hours respectively, the parameters showed variations at 48 and 72 hours that generally fluctuated around the control.Conclusions: The results indicate differential tissue responses to administered tramadol in different areas of the brain. The results suggest that the alterations in biogenic amines for the administration of tramadol are similar under both pain and no-pain conditions