RESUMO
Tramadol is a centrally acting analgesic agent used in the treatment of mild to moderate pain. It has a low affinity to opioid receptors and inhibits the reuptake of nor epinerphrine and serotonin producing an analgestic action by blocking nociceptive impulses in the spine. This work aimed to clarify toxic effects of tramadol hydrochloride on the brain and the possible protective role of naloxone hydrochloride. The study was carried out on 40 adult male albine rats that divided randomly into four equal groups: control; tramadol treated; naloxone treated and protective [tramadol and naloxone treated]. The regime of treatment was given daily for one month. Cerebral cortex of each animal was processed for histological, histochemical and immunohistochemical studies. The obtained results were analyzed morphometrically and statistically. Histologically and histochemically, cerebral cortex of tramadol treated rats showed many foci of degenerated cortical neurons with areas of vacuolations denoting cell loss. The degenerated neurons exhibited shrunken appearance with pyknotic nuclei. There were areas of haemorrhage in the superficial layers of cerebral cortex surrounded by glial cells and congestion of capillaries. Degenerated cortical neurons showed weak PAS reaction and pale staining with tuluodine blue. Immunohistochemically, glial cells showed positive immunoreactivity for GFAP in the form of intense react ion. On the other hand, histological, histochemical and immunohistochemical examination of the prophylactic group displayed normal appearance of most nerve cells and few cells appeared distorted. Area persent of GFAP immunoreactions in astrocytes in all groups showed significant increase in the treated group when compared with the control or prophylactic group. Toxic effects of tramadol should be kept in mind during chronic usage and general supportive treatment is recommended in over dosage beside naloxone as it could ameliorate some [not all] tramadol induced toxic effects