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. 2008 Feb;149(2):455-60.
doi: 10.1210/en.2007-0828. Epub 2007 Oct 25.

Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia

José M Garcia  1 , Juan P Cata, Patrick M Dougherty, Roy G Smith
Affiliations

Ghrelin prevents cisplatin-induced mechanical hyperalgesia and cachexia

José M Garcia et al. Endocrinology. 2008 Feb.

Abstract

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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Figures

Figure 1
Figure 1
A, Fifty percent mechanical threshold per group. *, P < 0.05 for cisplatin vs. saline group. §, P < 0.05 for cisplatin vs. cisplatin-ghrelin (Cisp-Ghrel) group.¶, P < 0.05 for cisplatin-ghrelin vs. saline group. B, Fifty percent mechanical threshold AUC per group. *, P < 0.05 for cisplatin vs. all other groups. §, P < 0.05 for cisplatin-ghrelin vs. all other groups.
Figure 2
Figure 2
Body weight gain per group. *, P < 0.05 for cisplatin vs. all other groups. **, P < 0.05 for cisplatin vs. ghrelin and cisplatin-ghrelin (Cisp-ghrelin)-treated animals, not vs. saline-treated animals.
Figure 3
Figure 3
Cumulative food intake per group divided in d 0–3 and 3–13. *, P < 0.05 compared with cisplatin-treated animals. Cisp-Ghr, Cisplatin-ghrelin.
Figure 4
Figure 4
A, Correlation between food intake and body weight changes (d 0–3). B, Correlation between food intake and body weight changes (d 3–13). C, Correlation between mechanical threshold and IGF-I changes at 24 h. D, Correlation between mechanical threshold and food intake (d 0–3). E, Correlation between mechanical threshold and weight change (d 0–3). Cisp-Ghr, Cisplatin-ghrelin; Ghrel, ghrelin.
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