Effects of the Co-Administration of Thyme and Tramadol on The Postnatal Development of Purkinje Neurons of The Albino Rat

Document Type : Original Article


1 Department of Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Egypt.

2 Department of Human Anatomy and Embryology, Faculty of Medicine, Assiut University, Egypt


Background:  Tramadol is a painkiller that works by acting on the central nervous system. Even though tramadol is regarded to have minimal misuse and dependence potential, it is increasingly being used in pregnant women in many countries throughout the world, notably in the Middle East, Africa, and West Asia, to relieve pain from rheumatoid arthritis, cancer, and other diseases. Aim of the work: To assess the harmful effects of tramadol on the postnatal development of the cerebellar Purkinje cells of rats and to evaluate the possible ameliorative effect of thyme if being administered with tramadol simultaneously. Material & Methods: Three sets of Forty-eight mature female albino rats were randomly organized into three equal groups; Group 1 (control), group 2 (tramadol treated) and group 3 ( tramadol+thyme treated). The rats' offspring of the fore mentioned three groups were further subdivided according to their ages into 3 subgroups (newborn, 10th, and 20th postnatal day). Group I have not received any treatment. Tramadol HCL (40 mg/Kg/day) dissolved in tab water was given orally to group B. Tramadol (40 mg/Kg/day) and thyme extract (500 mg/kg/day) were given orally to group C. From the first day of pregnancy until weaning, female rats were administered tramadol and thyme. For each of the three groups, the Purkinje cell layer of the cerebellar cortex of the rats' offspring (newborn, 10th, and 20th postnatal day) was then examined for histological, ultrastructural, immunohistochemical changes and morphometric analysis. Results: Histological, ultrastructural and immunohistochemistry studies showed that in GII there were neuronal frittering and apoptotic changes in the Purkinje neurons. In GIII, an improvement in histological, ultrastructural and immunohistochemical changes was observed. The morphometric results revealed that there was a significant statistical difference at 10th and 20th postnatal age whereas no recorded significant statistical difference at newborn age among the experimental groups. Conclusion: Tramadol use during pregnancy and breastfeeding had a neurotoxic impact on the development of Purkinje cells of the cerebellar cortex of rats. Thyme extract can ameliorate the tramadol's harmful effects; hence it may be useful in the therapy of tramadol neuronal damage if tramadol is required.