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Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Division of Endocrinology, Diabetes and Metabolism (J.M.G.), Michael E. DeBakey Veterans Affairs Medical Center, and Huffington Center on Aging (J.M.G., R.G.S.), Baylor College of Medicine, Houston, Texas 77030; and Department of Anesthesiology and Pain Medicine (J.P.C., P.M.D.), University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77002

Address all correspondence and requests for reprints to: José M. Garcia, M.D., Division of Endocrinology, Diabetes and Metabolism, Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Building 100, Room 3B-243, Houston, Texas 77030. E-mail: jgarcia1{at}bcm.edu.

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.

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