Tramadol exposure upregulated apoptosis, inflammation and autophagy in PC12 cells and rat's striatum: An in vitro- in vivo approach.

Aim And Background: Tramadol is a synthetic analogue of codeine, mostly prescribed for the alleviation of mild to moderate pains. It bears several side effects including emotional instability and anxiety. In this study, we focused on the alteration in expression of autophagic and apoptotic genes in PC-12 cells for our in vitro and structural and functional changes of striatum for our in vivo under chronic exposure of tramadol.

Methods: For in vitro side of the study, PC12 cells were exposed to tramadol (50 μM) and expression of apoptosis and autophagy genes were determined. In parallel, rats were daily treated with tramadol at doses of 50 mg/kg for three weeks for the in vivo side. Motor coordination, EMG, histopathology and gene expression were done.

Results: Our in vitro findings revealed that tramadol increased expression of apoptosis and autophagy genes in PC12 cells. Moreover, our in vivo results disclosed that tramadol not only provoked atrophy of rats' striatum, but also triggered microgliosis along with neuronal death in the striatum. Tramadol also reduced motor coordination and muscular activity.

Conclusion: Altogether, our data indicated that tramadol induced neurotoxicity in the PC12 cells via apoptosis and autophagy and in striatum chiefly through activation of neuroinflammatory and apoptotic responses.