Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

• Published in: Endocrinology (Philadelphia) 2008-02, Vol.149 (2), p.455-460
• Main Authors: Garcia, José M, Cata, Juan P, Dougherty, Patrick M, Smith, Roy G
• Format: Article
• Language: English
• Subjects: Animals; Anorexia; Antineoplastic Agents - toxicity; Attenuation; Behavior, Animal - drug effects; Biological and medical sciences; Body weight; Body Weight - drug effects; Brief Communication; Cachexia; Cachexia - chemically induced; Cachexia - prevention & control; Chemotherapy; Cisplatin; Cisplatin - toxicity; Drug Interactions; Eating - drug effects; Eating disorders; Food intake; Fundamental and applied biological sciences. Psychology; Ghrelin; Ghrelin - blood; Ghrelin - pharmacology; Growth hormones; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - prevention & control; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Male; Mechanical properties; Medical sciences; Neoplasms - drug therapy; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropathy; Neuroprotection; Pain perception; Prevention; Quality of life; Rats; Rats, Sprague-Dawley; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2007-0828

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coadministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications.