Background
Pain-associated depression is a symptom of many diseases such as cancer, and postoperative and myocardial infarction. Tramadol (TRM) is a centrally acting synthetic opioid, similar to an analgesic, used worldwide to treat severe pain with an anti-depressant-like effect. TRM is more popular abused among adults in most countries to relive pain and increase sexual activities. Thymoquinone (TQ), a volatile oil, is one of the main constituents of seeds. It has anti-inflammatory, antioxidant, anticonvulsant, antitussive, and anti-tumor effects.
The aim of work
The present study was designed to evaluate the effects of TRM on the structure of cerebral cortex of the adult male albino rats and the possible impact of using TQ to improve these changes and to test the analgesic, anti-depressant, and antioxidant effects of TRM and/or TQ.
Materials and methods
Forty-eight male albino rats weighting 180–200 g were used in the present study. The rats were divided into four groups: control group (GI): 12 rats received food and water. TQ group (GII): 12 rats received an oral dose of TQ (20 mg/kg) for 4 weeks. TRM group (GIII): 12 rats received an oral dose of TRM HCl (50 mg/kg) for 4 weeks. Combined group (GIV): 12 rats received both TRM (50 mg/kg) and TQ (20 mg/kg) for 4 weeks.
Results
TQ supplementation significantly increased the analgesic effect of TRM after acute and chronic treatment by the thermal and chemical methods and attenuated the development of tolerance. TQ also significantly improved the anti-depressant effect of TRM. Furthermore, TQ significantly increased the suppressed levels of glutathione content and activities of superoxide dismutase, catalase, and glutathione peroxidase induced by TRM. It also significantly reduced the elevated levels of malondialdehyde and nitric oxide caused by TRM. Histological examination of TRM-treated cerebral cortex showed distortion of its layers, increased vascularity, and cellularity, with a significantly increased number of apoptotic cells. TRM also induced a significant increase in the mean area percentage of both apoptotic index and the optical density of BAX immune-stain compared with the control group. These changes were improved in TQ-treated rats.
Conclusion
TQ supplementation improved the analgesic, anti-depressant effects of TRM, with an improvement in the cerebral cortex structure and antioxidant markers and amelioration of oxidative stress markers. Furthermore, it attenuated TRM tolerance and neurotoxic effects.