Objective: Tramadol is favorably used for relief of moderate and severe pain. Over 30% of Parkinson's disease (PD) patients experience persistent pain that has a negative impact on their quality of life. However, its physiological effect in such disorder has not been studied. The current study aimed at investigating the neurochemical and histopathological changes resulting from tramadol administration to experimental PD- induced by rotenone in rats.
Methodology: Forty adult male Sprague-Dawley rats were allocated into 5 equal groups; Group 1(control) received saline p.o and DMSO, s.c., Group 2(Rotenone) received rotenone (1.5 mg/kg, s.c., every other day for 12 days), Group 3 (Tramadol) received tramadol HCl given p.o., daily at doses of 20 mg/kg, Group 4 (Rot-Trama 10) PD-induced with rotenone and treated with tramadol HCl, 10 mg/kg, p.o., daily, Group 5(Rot-Trama 20) PD-induced with rotenone and treated with tramadol HCl, 20 mg/kg, p.o., daily.
Results : PD-induced rats exhibited significantly reduced dopamine (DA) content (- 33.0%), increased serotonin ( 5-HT) content (+ 11.5%), but no change in 5-hydroxyindole acetic acid (5-HIAA) compared to vehicle-treated counterparts. Rotenone also inhibited both brain paraoxonase 1 (PON1) and acetylcholinesterase (AChE) activities and increased brain oxidative stress causing reduced glutathione depletion by 32% and increasing thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) by 43% and 81%, respectively. Rotenone caused the appearance of apoptotic neurons with cytoplasmic vacoulations. On the other hand, tramadol -treated control rats showed increased DA (74%), 5-HT (23%), 5-HIAA (50%) contents and decreased serotonin turnover (18.0%) without causing oxidative stress. In rotenone-intoxicated rats, tramadol (10 or 20 mg/kg) increased brain dopamine and at 20 mg/kg increased 5-HT and 5-HIAA. The drug increased PON-1 activity, restored AChE activity and alleviated the changes in lipid peroxidation and reduced glutathione, increased tumour necrosis factor-alpha (TNF-α) without changing the histopathological changes caused by rotenone. Conclusion: These results indicate that short-term use of tramadol in an experimentally-induced PD has dual effects that should be carefully weighed. Tramadol decreased oxidative stress and restored normal DA content and AChE activity that can help in PD. However, the drug resulted in increased proinflammatory cytokine TNF-α and 5-HT level.