E.M. Frantsiyants, I.M. Kotieva, V.A. Bandovkina, E.I. Surikova, I.V. Kaplieva, I.V. Neskubina, N.D. Cheryarina
National Medical Research Center of Oncology, Rostov-on-Don
Surikova Ekaterina I. ― Cand. Biol. Sc., senior researcher at Laboratory of Malignant Tumor Pathogenesis Study of National Medical Research Center of Oncology,
63 14th line, Rostov-on-Don, Russian Federation, 344037, tel.: (863) 200-10-00 ext. 482 or -483, +7-904-501-83-62, e-mail: firstname.lastname@example.org
Abstract. Despite significant progress in understanding the neurophysiology and psychology of pain, fundamental and clinical aspects of the problem of chronic pain remain largely unresolved. Tumor development and chronic pain are pronounced stress factors with the mechanisms involving many growth factors, hormones and neurotransmitters.
The aim of the study was to reveal mechanisms of the condition formation for stimulating tumor growth and activating angiogenesis under the influence of chronic neuropathic pain (CNP).
Material and methods. The study included 56 female С57BL/6 mice. Animals of the main group underwent transplantation of В16/F10 melanoma 2 weeks after bilateral sciatic nerve ligation, in the comparison group ― only melanoma transplantation. Levels of VEGF (A and C) and their soluble receptors (R1 and R3), sex hormones and their receptors, prolactin, biogenic amines and components of the NO-system were measured by standard ELISA and RIA methods in the skin (intact animals and with only CNP) and tumor tissues (comparison and main groups). Statistical analysis of results was performed in the Statistica 6.0 program, the significance of differences was assessed by the Student’s t-test and the Mann ― Witney criterion. Differences were considered significant at p<0.05.
Results. The main group demonstrated lower survival of mice, earlier metastasis onset and atypical metastatic sites. Tumor levels of VEGF-A and VEGF-C, NOS-3, NOS-2, citrulline and ADMA were elevated. Increased concentrations of estrone, progesterone, prolactin and receptors to estrogens, androgens and progesterone were found. The balance of biogenic amines was changed: adrenaline and serotonin levels increased, while noradrenaline and dopamine decreased.
Conclusions. The results can confirm the systemic CNP influence that significantly changes the functions of vasoactive NO- and neurohumoral systems leading to the formation of conditions for angiogenesis activation and tumor growth.
Key words: mice, B16/F10 melanoma, chronic pain, pathogenesis of tumor growth, skin, tumor, growth factors, angiogenesis, sex hormones, biogenic amines, nitric oxide.