CHRONIC NEUROGENIC PAIN PROMOTES DEVELOPMENT AND GROWTH OF M1 SARCOMA CHANGING LOCAL LEVELS OF GROWTH FACTORS

Abstract

Introduction. The influence of chronic neurogenic pain on local levels of growth factors in the lung and the risk of lung cancer development has been little studied.The purpose of the study was to analyze the levels of VEGF, TGF-β, IGF-I, IGF-II, FGF-21 and receptors of VEGFR2, TGF-βR2 in the lungs of white outbred rats with chronic neurogenic pain after intravenous injection of M1 sarcoma.Material and Methods. A total of 28 white outbred male rats weighing 200–250 g were divided into 4 groups: 1 – sham-operated animals (control group) (n=7); 2 – animals with chronic neurogenic pain (n=7); 3 – sham-operated animals with intravenous injection of M1 sarcoma (n=7); 4 – rats with intravenous injection of M1 sarcoma in presence of chronic neurogenic pain (n=7). Animals were decapitated, the lungs were harvested on ice; 10 % cytosolic fractions were prepared in 0.1 M potassium phosphate buffer pH 7.4 containing 0.1 % Tween-20 and 1 % BSA. Levels of VEGFR2, TGF-β and receptors of TGF-βR2, IGF-I, IGF-II (CUSABIO BIOTECH Co., Ltd., China) and FGF21 (BioVender, Czech Republic) were determined by ELISA. The data were statistically processed using Statistica 10.0 software.Results. Multifocal tumors of sarcoma in the lungs were determined only in the group of rats with chronic neurogenic pain after intravenous transplantation of M1 sarcoma. In the lungs of sham-operated animals, tumor foci were not detected after M1 sarcoma transplantation. Lung tissues with M1 growth and presence of chronic neurogenic pain demonstrated decreased VEGF-А levels with increased concentrations of TGFβ, IGF-I, IGF-II and FGF-21. Chronic neurogenic pain directly or indirectly influenced levels of some growth factors in the lung, and altered cell homeostasis making possible transplantation of M1 sarcoma into the lung.