Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats

• Published in: Neuroscience letters Vol. 479; no. 3; pp. 226 - 230
• Main Authors: Guneli, Ensari, Onal, Aytul, Ates, Mehmet, Bagriyanik, Hüsnü Alper, Resmi, Halil, Orhan, Cahide Elif, Kolatan, Hatice Efsun, Gumustekin, Mukaddes
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 02.08.2010; Elsevier
• Subjects: Analgesics - pharmacology; Analgesics - therapeutic use; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Chronic Disease; Constriction, Pathologic; Cytokines - metabolism; Fundamental and applied biological sciences. Psychology; Ghrelin; Ghrelin - pharmacology; Ghrelin - therapeutic use; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Interleukin-1beta - metabolism; Male; Neuropathic pain; Pain - drug therapy; Pain - metabolism; Pain - physiopathology; Proinflammatory cytokines; Rats; Rats, Wistar; Sciatic Nerve - drug effects; Sciatic Nerve - injuries; Sciatic Nerve - pathology; Spinal Cord - metabolism; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: nervous system and sense organs; Rats; Proinflammatory cytokines; Ghrelin; Neuropathic pain; Rat; Rodentia; Cytokine; Inflammation; Vertebrata; Chronic; Mammalia; Pain; Animal; Lesion; Sciatic nerve
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.05.066

Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CCI-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100 μg/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-α, IL-1β and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-α and IL-1β levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-α and IL-1β. Thus ghrelin may be a promising peptide in the management of neuropathic pain.