Publication: Sıçanlarda intraserebroventriküler tramadol uygulanımının nörotoksik etki açısından araştırılması
Abstract
Bu çalışmanın amacı, sıçanlarda intraserebroventriküler yoldan verilen tramadolün, spinal korddaki etkisinin histopatolojik açıdan incelenmesidir. Ağırlıkları 200-300 g arasında değişen, her iki cinsten, 18 erişkin sıçan çalışmaya dahil edildi. Intraperitoııeal yoldan 100 mg/kg ketamin hidroklorür ve 0.75 mg/kg klorpromazin ile anestezileri sağlanan sıçanlara, stereotaksik olarak, sol pariyetal ventrikül üzerine gelecek şekilde kılavuz kanül yerleştirildi. Uç gruba ayrılan sıçanlardan I. gruba (n=7) 10 uL 0.9 SF içerisinde 6 ug tramadol tek doz olarak, H. gruba (n=7) 10 uL 0.9 SF içerisinde 6 mg tramadol bir ve ikinci günlerde birer kez olmak üzere, III. gruba (n=4) ise 10 uL 0.9 SF tek doz olarak kanüllerden enjekte edildi. Sıçanlar genel davranış, motor koordinasyon ve tonus açısından değerlendirildi ve son dozdan 48 st sonra sakrifiye edilerek beyin ve spinal koraları ışık mikroskobunda incelendi. Tramadol verilen her iki gruptaki yedi sıçanın üç tanesinin spinal koralarında glial hücre reaksiyonuna; Grup Fde beş, Grup Il'de altı, Grup IU'de ise dört sıçanın hem serebellum hem de spinal koralarında kırınızı nörona rastlanıldı. Ancak bu bulgular arasında fark bulunamadı (p>0.05). Sonuç olarak; sıçanlarda analjezik dozda tramadolün, spinal kordda tek ve tekrarlanan kullanımının nörotoksik bir etki oluşturmadığı, ancak farklı doz ve konsantrasyonların elektron mikroskopisi ile değerlendirileceği çalışmalar yapılması gerektiği kanısına varıldı.
The aim of this study was to carry out behavioural and histological examinations in rats to determine whether intracerebroventricular administration of tramadol produces spinal cord lesions. Eighteen Sprague-Dawley rats, weighing 200-300 g were implanted with an intracerebroventricular cannula after anaesthetizing with ketamine hydrochloride (100 mg/kg) and chlorpromazine (0.75 mg/kg) intraperitoneally. They were assigned into three groups, receiving either a single injection of 6 ug tramadol (n=7), two repetitive injections On consecutive days of 6 jj,g tramadol (n=7) or saline (n=4) in 10 uL volumes. Neurobehavioural changes were examined until the day of killing. Animals were killed 48 hours after the last injection and brain and spinal cord section slides were examined with light microscopy. Gliosis was seen in the spinal cords of three of seven rats in group I and II. Five rats in group I, six in group II, and four in group III had red neurons in cerebellum and spinal cord sections. There was no dif-ference between the groups (p>0.05). In conclusion, intracerebroventricular administration of tramadol in rat produced no abnormal behavioural and histopathologic results. But further studies with different doses and with the examination of the sections under electron microscopy should be done before using in humans.
The aim of this study was to carry out behavioural and histological examinations in rats to determine whether intracerebroventricular administration of tramadol produces spinal cord lesions. Eighteen Sprague-Dawley rats, weighing 200-300 g were implanted with an intracerebroventricular cannula after anaesthetizing with ketamine hydrochloride (100 mg/kg) and chlorpromazine (0.75 mg/kg) intraperitoneally. They were assigned into three groups, receiving either a single injection of 6 ug tramadol (n=7), two repetitive injections On consecutive days of 6 jj,g tramadol (n=7) or saline (n=4) in 10 uL volumes. Neurobehavioural changes were examined until the day of killing. Animals were killed 48 hours after the last injection and brain and spinal cord section slides were examined with light microscopy. Gliosis was seen in the spinal cords of three of seven rats in group I and II. Five rats in group I, six in group II, and four in group III had red neurons in cerebellum and spinal cord sections. There was no dif-ference between the groups (p>0.05). In conclusion, intracerebroventricular administration of tramadol in rat produced no abnormal behavioural and histopathologic results. But further studies with different doses and with the examination of the sections under electron microscopy should be done before using in humans.