Involvement of Endothelin and ETAEndothelin Receptor in Mechanical Allodynia in Mice Given Orthotopic Melanoma Inoculation

• Main Authors: Masahide Fujita, Tsugunobu Andoh, Ikuo Saiki, Yasushi Kuraishi
• Format: Article
• Language: English
• Published: Elsevier 2008-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319315208

We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ETA- receptor antagonist BQ-123 (0.3 –3 nmol/site), but not the ETB-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ETA, but not ETB, receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ETAreceptor are at least partly involved in the induction of pain induced by melanoma cell inoculation. Keywords:: cancer pain, endothelin, endothelin receptor, allodynia, licking