Structural myocardial catastrophe under the influence of chronic neurogenic pain due to development of B16 melanoma in female mice
Authors: Shikhlyarova A.I. , Frantsiyants E.M. , Kaplieva I.V. , Zhukova G.V. , Neskubina I.V. , Nepomnyashchaya E.M. , Trepitaki L.K. , Kozel Y.Yu. , Yengibaryan M.A. , Vereskunova A.A. , Babieva S.M. , Legostaev V.M. , Kharagezov D.A. , Volkova V.L. , Kit O.I. 
Published: June 2022

Topicality. Most of the inhabitants on the planet have directly experienced certain manifestations of pain, and in the case of chronic pain sensations, some significant changes may occur not only in the psycho-emotional sphere of a human individual, but also some functional alterations in the life maintenance systems. There are two global problems of medicine which are associated with oncology and cardiovascular pathology, and, taking into account the prevalence of pain symptoms of various etiologies, a pathological triangle is formed, each side of which affects the overall configuration thereof. There is a need to understand these pathological relationships in order to determine the real possibilities of breaking them and correcting such common complex life situations. Any attempt to create a concept and visually verify the real pathological changes in the heart, when modeling a combination of chronic neurogenic pain and a malignant process, is relevant that is the aim of this research work. We targeted the morphological picture of the heart in female mice with chronic neurogenic pain (CNP) and the growth of B16 melanoma and found a rather tough scenario of unfolded events. Materials and methods. We used female mice of the C57BL/6 line with a normal genotype. Chronic neurogenic pain (CNP) was produced by bilateral ligation of the sciatic nerve. Against that background, all animals were subcutaneously transplanted with melanoma B16/F10. After decapitation, the isolated heart preparations were carried out according to the stages of morphological preparation for staining sections with hematoxylin-eosin, followed by morphological examination of the structure with the Leica DM LS2 microscope furnished with an Olympus optical.C-5050 Zoom video camera and Morfotest software. Photographing was conducted with magnifications x10, x40, x100. Results. A pronounced pro-oncogenic effect of pain stimulation of the neurogenic nature was revealed, which consisted in an earlier manifestation of the tumor growth, large-scale metastasizing even to atypical target organs, and the formation of a pre-terminal state at an earlier time. At the same time, morphological correlates of prolonged damage to the heart at the level of the valves and the ventricular wall were determined, the key elements of which were ischemia, total longitudinal splitting of muscle fiber bundles, blood filling of large vessels, hemorrhages, deep cell dystrophy of cardiomyocytes, myolysis, macrofocal necrosis (myomalacia), an accumulation of necrotic masses, fibrosis and eosinophilic infiltration. Visualization of the nuclei of cardiomyocytes indirectly indicated the switch of the death program to the non-apoptotic pathway, i.e. necrosis as a result from the “tumor-caused” depletion of the energy reserves of cardiomyocytes. Conclusion. The simulated hypertrophied manifestations of myocardial catastrophe in the experiment expand the concept of a prolonged infarction and provide a basis for predicting and preventing a negative course of events in difficult patients with persistent pain syndromes and comorbid pathology against the background of the development of a malignant process.