Cerebral cortical changes in adult albino rats under the effect of tramadol and its withdrawal: Histological and morphometric study

Abstract

Introduction: Analgesics are the most commonly used drugs worldwide. Tramadol hydrochloride (opioid) is a synthetic centrally acting analgesic agent used for treating moderate to severe pain with less side effects than traditional opioid medications. Aim of the Work: To study the histological and morphometric changes of the cerebral cortex in adult albino rats after tramadol hydrochloride administration and the effect of its withdrawal. Materials and Methods: Twenty four adult albino rats were used regardless sex, divided into 3 groups: a control group: consisted of 8 rats and were furtherly subdivided into two equal subgroups: a subgroup, rats were kept without any medication for 4 weeks and another where rats received saline daily by intraperitoneal injection for 4 weeks. Tramadol Group included 8 rats received the therapeutic dose of tramadol intraperitoneally for 4 weeks. Withdrawal group included 8 rats received the same dose as tramadol group then kept for 4 weeks later without treatment to study the effect of its withdrawal. The obtained specimens were examined by both light and electron microscopy. Results: The control group showed the normal histological picture of the cerebral cortex. The Tramadol group revealed loss of organization of cerebral cortex layers, some pyramidal and granular cells with pyknotic nuclei and surrounded by haloes. Astrocytes showed hypertrophy of their cell bodies with increased thickening of their processes. Ultrastructurally, the pyramidal cells showed heterochromatic nuclei with marked indentations of their membranes and the myelinated axons showed splitting of myelin sheaths with swollen mitochondria in their axoplasm. Withdrawal group showed evidence of improvement as compared to the tramadol group. Conclusion: Opioid analgesics (Tramadol hydrochloride) when the therapeutic dose is used for a long time led to marked damaging effect on the cerebral cortex, However, its withdrawal resulted in improvement to a lesser extent of their damaging effects.