Mechanisms of cancellation by pain of genetically determined inhibition of a malignant tumor growth in experiment

Abstract

Aims are to study the nature of the processes of carcinogenesis of experimental B16/F10 melanoma in uPA gene knockout mice modified by chronic neurogenic pain and investigate some electrophysiological mechanisms of melanoma development. Materials and methods. We used 48 C57BL/6-PlautmI. IBug-ThisPlau6FDhu/GFDhu mice of both genders with urokinase gene knockout and 102 C57BL/6 mice of both genders with the normal genotype. Chronic neurogenic pain (CNP) was produced due to bilateral ligation of the sciatic nerve. Against the above background, all animals were transplanted with B16/F10 melanoma. To study the mechanism of CNP, studies of the intracellular electrophysiological activity of neurons of the central nervous system of the snail Helix pomatia in the body in vivo were carried out. CNP was reproduced by dosed pressing of four main nerves with Fresnel hairs that with time turned into increasing pain. Membrane potential (MP), action potential (AP) and firing rate (FR) parameters of intracellular bio-potentials of the command neuron RPaG3, continuously recorded using an ultrathin glass microelectrode for 4-5 days, were analyzed. Results. It was detected that an activation of cancerogenesis during the modification of the progression of experimental B16/ F10 melanoma in C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice with uPA gene knockout using CNP is accompanied by a 2-fold acceleration in the time of tumor production, stimulation of the growth of the primary tumor nodes from 1.05±0.08 cm3 to 9.50±0.98 cm3 (p<0.001) and multiple metastasizing to the lungs, a reduction in the life span from 34.67±0.67 to 21.33±2.19 days (p<0.001) <0.05) in the genetically modified mice, by changing some gender-specific characteristics of the progression of the malignant process. The neuropathic nature of pain resulting from command neuron compression or ligation of the sciatic nerves is essentially identical to the implementation of genetic programs responsible for the control of life and death, reproducing events in carcinogenesis with the progression of a malignant tumor. Conclusion. The initiation and chronization of pain at the local level of the nervous system can lead to generalization of the pain syndrome and contribute to the cancellation of genetically predetermined programs of carcinogenesis.