Influence of Chronic Neurogenic Pain on the Dynamics of the No-System Functioning During Melanoma B16/F10 Growth in Male Mice

Abstract

Since B16/F10 melanoma demonstrated gender differences in its growth in the presence of chronic neuropathic pain (cnp) and changes in the system of proangiogenic growth factors, the aim of the study was to analyze levels of components of the no-system in male mice during the growth of transplantable B16/F10 melanoma in the presence of cnp.Material and Methods. 66 male mice С57Вl/6 were used in the experiment. A model of subcutaneous growth of B16/F10 melanoma (during 3 weeks) was created in the cnp presence (sciatic nerve ligation). Concentrations of nos-2, nos-3, l-arginine, citrulline, total nitrite, nitrotyrosine and adma were determined by elisa in intact and tumor tissues.Results. A significant increase in levels of no-synthases was revealed in the skin and tumor tissues in the tumor growth with cnp from week 1, as well as a decrease in the level of total nitrite in the skin, multidirectional dynamics of adma and arginine levels, a steadily increased level of citrulline in the skin and tumor in the dynamics of tumor growth with cnp.Conclusions. Male mice with B16 melanoma growing in the presence of cnp demonstrated a more active functioning of the no-system already from week 1, compared to standard tumor growth, which might result in a greater rate of growth of melanoma with cnp. Significantly higher skin and tumor levels of citrulline in males were a distinctive feature, in contrast to melanoma with standard growth, which could be the result of inhibition of arginine synthesis and formation of a tumor auxotrophic for arginine.