Rostov State Medical University, Rostov-on-Don, Russian Federation
Inga Movlievna Kotieva , Elena M. Frantsiyants
Background: Patients with oncological pathology, especially with the progression of the disease, often have chronic pain[1]. Pain effects singly can cause dysfunction of the vascular system, which could be an additional risk of the tumor process progression. The aim of the study was to identify gender-specific chronic pain effects on some vascular endothelial growth factors and their skin receptors in the B16/F10 melanoma model. Methods: The study was conducted on mice of the C57BL/6 line (females, males; age 8 weeks, weight 21-22 g, n = 48, 12 animals in each group). Two weeks after the ligation of the sciatic nerve melanoma B16/F10 was transplanted under the skin in the back of the main groups of animals (I- females, II-males); control groups were held the same procedure without ligation (III-females, IV-males). The levels of VEGFA, sVEGFR1, VEGFC, sVEGFR3 were determined in intact skin by ELISA. All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Results: Chronic pain contributed to the accumulation of VEGF-A, sVEGF-R1, VEGF-C in the skin and the reduction of sVEGF-R3 in all animals: in females - 2.7 times, 2.9 times, 6.1 times and 6.1 times, accordingly, in males - 3.1 times, 3.7 times, 3.5 times and 7.2 times, accordingly. Consequently, in males the amplitude of fluctuations of VEGF and their receptors in the skin against the background of pain was higher than in females, except for VEGF-C, the amount of which increased in females more than in males, despite its identical initial level in the skin of animals of both sexes. As a result, the skin of males with pain contained more VEGF-A, sVEGF-R1 and sVEGF-R3, accordingly, by 1.4 times (p < 0.05), 2.0 times and 1.9 times (p < 0.05) and less VEGF-C - by 1.8 times (p < 0.05). Conclusions: Chronic neuropathic pain had different effects on changes in the level of vascular endothelial growth factors and their receptors in intact skin in females and males of melanoma B16/F10 tumor carriers. The gender characteristics of the effect of chronic pain on neoangiogenesis may be associated with different rates of growth and development of the malignant process in male and female mice in the experiment. References [1] Kotieva I.M. et al. Chronic pain and accumulation of growth factors in perifocal tissues of melanoma and impact on malignancy and early metastasis. Journal of Clinical Oncology. 2018. Т. 36. № S15. С. e21621.
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