Fujita Masahide, Andoh Tsugunobu, Saiki Ikuo, Kuraishi Yasushi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Japan.
J Pharmacol Sci. 2008 Feb;106(2):257-63. doi: 10.1254/jphs.fp0072051. Epub 2008 Feb 9.
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 ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-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 ET(A), but not ET(B), 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 ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.
我们研究了内皮素（ET）是否参与小鼠皮肤癌疼痛。将B16 - BL6黑色素瘤细胞原位接种到后爪足底区域可使C57BL / 6小鼠产生明显的机械性异常性疼痛。足底注射ET（A）受体拮抗剂BQ - 123（0.3 - 3 nmol/部位）可抑制已发生黑色素瘤的小鼠的机械性异常性疼痛，而ET（B）受体拮抗剂BQ - 788（1和3 nmol/部位）则无此作用。在未接触过肿瘤的小鼠中，足底注射从爪部生长的黑色素瘤制备的肿瘤提取物（1和3 mg/部位）可产生机械性异常性疼痛，该疼痛可被3和10 nmol/部位剂量的BQ - 123和BQ - 788抑制。足底注射ET - 1（1和10 pmol/部位）可引发舔舐行为，在荷瘤后爪中这种行为增强。BQ - 123（3和10 nmol/部位）可抑制ET - 1（10 pmol/部位）诱导的舔舐行为。接种侧背根神经节中ET（A）受体而非ET（B）受体的mRNA水平显著升高。培养的B16 - BL6细胞含有ET，黑色素瘤肿块随着生长而使ET浓度增加。这些结果表明，ET - 1和ET（A）受体至少部分参与黑色素瘤细胞接种诱导的疼痛。
