Infl uence of neurogenic chronic pain on indicators of kallikreinkinin system in skin of female mice in dynamics of В16/F10 melanoma development

Abstract

Objective: determination of levels of the kallikrein-kinin system (KKS) indicators in cutaneous melanoma and in the skin not associated with tumor in female mice with chronic neurogenic pain in the dynamics of В16/F10 melanoma growth. Materials and methods: the study included 8 weeks old female С57ВL/6 mice weighing 24-26 g (n=132). Th e animals were divided into 4 groups: 64 – В16/F10 melanoma with chronic neurogenic pain (main group), 22 – chronic neurogenic pain without melanoma, 27 – В16/F10 melanoma only (comparison group), 19 – intact mice. KKS parameters were determined by ELISA. Statistical processing of results was performing using the Statistica 10 program and the Wilcoxon test. Results: chronic pain infl uenced the development of transplantable В16/F10 melanoma: tumors in animals of the main group appeared 1 week aft er the transplantation and were bifocal; 100% metastasis to the liver, lungs and to non-typical sites (the heart and uterus). Tumors in mice of the comparison group appeared in 2 weeks, and metastases in 4 weeks. Th e mean survival was 19.17±1.35 days in the main group and 30.25±1.67 days in the comparison group. In the skin of mice of the main group, we observed progressive kininogen consumption, KLK-1 depletion from the second week of the tumor growth, and its accumulation in the tumor with its maximum by the end of week 3. KLK-14 signifi cantly increased in the skin; in the tumor it stabilized aft er an increase in week 1. KKS parameters diff ered signifi cantly in the skin and tumor tissues of mice in compared groups. Conclusions : Chronic neurogenic pain causes a radical reorganization of KKS metabolism in the skin of intact mice: an increase in kininogen and prekallikrein and a decrease in KLK-1. B16/F10 melanoma transplantation with chronic neurogenic pain preserves the increase of prekallikrein in the skin, but increases as well its consumption in tumor tissue simultaneously with the activation of KLK-1 (in the skin until its exhaustion) and KLK-14.