Laboratory study The effect of exogenous melatonin administration on trabecular width, ligament thickness and TGF-b 1 expression in degenerated intervertebral disk tissue in the rat Mehmet Turgut a, * , Gu ¨lperi O ¨ ktem b , Serap Uslu b , Mine Ertem Yurtseven b , Hu ¨ seyin Aktug ˘ b , Ays ßegu ¨l Uysal b a Department of Neurosurgery, Adnan Menderes University School of Medicine, Aydın, Turkey b Department of Embryology & Histology, Ege University School of Medicine, Izmir,Turkey Received 28 February 2005; accepted 3 March 2005 Abstract Intervertebral disk (IVD) degeneration, a complex pathological condition of varying origins, causes low back pain. Degenerative changes in IVD tissue affect the adjacent vertebral structure, resulting in a decreased vertebral trabecular width. It has been suggested that transforming growth factor-beta 1 (TGF-b 1 ) may have a role in the repair of connective tissue, as it occurs in the IVD degen- eration process. In this study, we investigated the effects of exogenous melatonin (MEL) administration on vertebral trabecular width, ligament thickness and TGF-b 1 expression in degenerated IVD tissue. Fifteen adult male Swiss Albino rats were divided randomly into three groups; nonoperated control, operated degeneration, and MEL treatment groups. In the operated degeneration and MEL treatment groups, cuts were made parallel to the end plates in the posterior annulus fibrosus at the fifth and tenth vertebral segments of the tail to induce IVD degeneration. In each group, TGF-b 1 immunoreactivity and morphometry of vertebral trabecular width and anterior and posterior ligament thickness were evaluated. Histologically, disorganisation and irregularity of collagen fibres was seen in the degenerated (operated) IVD. Increased TGF-b 1 expression in multinuclear chondrocytes was also observed as was decreased vertebral trabecular width. Importantly, the reduction of trabecular width observed in the operated degenerated group was reversed after MEL administration (p < 0.0001). Similarly, TGF-b 1 expression in multinuclear chondrocytes was dramatically increased after exogenous MEL application. Thus, there was a regression in histopathological changes after MEL treatment, with disk appearances similar to those of the control group. Based on our findings, we suggest that MEL activates the recovery process in the degenerated IVD tissue, possibly by stimulating TGF-b 1 activity. This is the first report investigating the involvement of the pineal hormone MEL in the repair of rat IVD. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Melatonin; TGF-b 1 ; Degeneration; Intervertebral disk; Vertebral trabecula; Rat 1. Introduction Morphologically, the intervertebral disk (IVD) consists of three parts: the nucleus pulposus, containing amorphous substance rich in proteoglycans; the annulus fibrosus, com- posed of concentric lamellae rich in collagen; and the car- tilage endplate at the cranial and caudal vertebral interface of the disk. 1,2 In both animals and humans, the IVD characteristically consists largely of extracellular ma- trix (ECM), particularly proteoglycan, with a low cell den- sity. In many respects, this leaves the IVD prone to degeneration, as ECM lacks nociceptive feedback to detect and limit damage. 1 It is well known that degeneration and age-related changes are characterised by biochemical and structural changes of the components of the IVD. 1,3 As a 0967-5868/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2005.03.037 * Corresponding author. Present address: Cumhuriyet Mahallesi, Cumhuriyet Caddesi, No: 6, Daire: 7, TR-09020 Aydın, Turkey. Tel.: +90 256 2134874; fax: +90 256 2120146/32172. E-mail address: drmturgut@yahoo.com (M. Turgut). www.elsevier.com/locate/jocn Journal of Clinical Neuroscience 13 (2006) 357–363