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 CC-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 mu g/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1 beta 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-alpha and IL-1 beta 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-alpha and IL-1 beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain. (C) 2010 Elsevier Ireland Ltd. All rights reserved.