Chronic neurogenic pain is responsible for changes in concentrations of biogenic amines in the brain in urokinase knockout mice with melanoma B16/F10

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 C57BL/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 (n= 6) as follows: the intact animals, the chronic neurogenic pain mice (CNP), the mice with the growth of inoculated melanoma (B16/F10) and the mice with combination melanoma growth plus chronic neurogenic pain (B16/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 inoculatedmelanoma B16/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 B16/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 B16/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.