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Original research

Chronic neurogenic pain is responsible for changes in concentrations of biogenic amines in the brain in urokinase knockout mice with melanoma В16/F10

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Abstract

Our aim is to study special features of actions and effects of chronic neurogenic pain on concentrations of biogenic amines in the brain in tumor-bearing urokinase knockout mice (uPA).

Materials and methods

Our research work has been conducted in female/male mice line С57ВL/6 (uPA+/+) n=48 and line C57BL/6-Plautm1.1Bug-ThisPlauGFDhu/GFDhu (uPA) -/-) n = 48 with targeted mutation of protein incapable of binding to receptor of the urokinase-type plasminogen activator, i.e. in the urokinase knockout (uPA) mice. The animals of each line have been divided into subgroups (п= 6) as follows: the intact animals, the chronic neurogenic pain mice (CNP), the mice with the growth of inoculated melanoma (В16/F10) and the mice with combination melanoma growth plus chronic neurogenic pain (В16/F10 + CNP). In 10% of the brain homogenates, with the use of standard analysis system method ELISA (Cusabio. China), we have determined concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine, serotonin (5HT) and 5-hydroxyindoleacetic acid (5-HIAA). Obtained statistic data have been processed using the Statistica 10.0 package.

Results

The concentration of biogenic amines in the brain in the intact uPA-/- mice has been found to be higher than in the intact uPA+/+ animals, and the response to the growth of inoculated melanoma В16/F10 and CNP under single-factor action and combined-action variants depends both on the sex and the condition of the urokinase gene. In the uPA-/- female/male mice in response to the only CNP and the only В16/F10 growth the serotonergic system in the brain has been activated. In contrast thereto, in case of the melanoma growth against the CNP background, we have revealed a decrease in the level of 5HT, DA in the female/male mice and NA in the female animals.

Conclusion

One of the factors resulting in cancellation of the genetically determined inhibition of the growth of inoculated melanoma В16/F10 under its combination with developing CNP in the uPA-/- mice is suppression of their noradrenergic, serotonergic and dopaminergic systems, initially activated in the intact uPA-/- animals to compensate their urokinase deficit.

Imprint

Elena М. Frantsiyants, Valeriya А. Bandovkina, Irina V. Kaplieva, Ekaterina I. Surikova, Irina V. Neskubina, Natalia D. Cheryarina, Viktoria V. Pozdnyakova, Oleg I. Kit. Chronic neurogenic pain is responsible for changes in concentrations of biogenic amines in the brain in urokinase knockout mice with melanoma В16/F10. Cardiometry; Issue 17; November 2020; p.49-57; DOI: 10.12710/cardiometry.2020.17.49-57; Available from: http://www.cardiometry.net/issues/no17-november-2020/chronic-neurogenic-pain

Keywords

С57/В16 mice line,  UPA,  Brain biogenic amines,  Chronic neurogenic pain,  Inoculated melanoma В16/F10
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