Pain syndrome in adenomyosis. Finding new pathogenesis links and non-hormonal correction opportunities. Literature review

Adenomyosis is characterized by polymorphism of clinical manifestations and is the cause of chronic pelvic pain associated with endometriosis in 53–80% of cases. Heavy dysmenorrhea in adenomyosis is a key factor that reduces the quality of life and, moreover chronic pain reduces stress resistance and launches the rehabilitation cytokines cascade, which causes exacerbation of endometriosis. Formation of painful syndrome with adenomyosis may be due to: changes in neurohumoral regulation, stimulation of nerves and blood vessels growth and myometrium inflammatory remodeling against the background of circulatory disorders and vascular sclerosis. These processes lead to violation of neuroimmune relationships that determine the increase in the number and sensitivity of nociceptors against the background of the chronic immuno-inflammatory process in endometrials and myometry. Experimental studies have shown that the supraspinal role of the nitric oxide (NO) is to indirect mechanical nociceptive reflexes. The dose-dependent L-arginine role in the pain syndrome formation also was shown; it was found that small doses of L-arginine lead to the activation of nNO-synthase and analgesic effect. Large doses are activated by cotorphine synthase to form a dipeptide of cortorphine (L-tyrosine-L-arginine), which induces the met-enkephalin release and analgesic effect. Individual studies have demonstrated a decrease in the symptoms of urinary pain syndrome during L-arginine treatment, which made it possible to include it into the European Association of Urologists recommendations on the chronic pelvic pain treatment in 2017. Clinical comparative study (2013) of the NO donator (L-arginine) effectiveness in the treatment of endometriosis-associated intermenstrual pelvic pain and dysmenorrhea showed a high efficiency of a 3-month course of combination therapy (dienogest 2 mg + Tivortin 4.2 g). Supplement of basic therapy by NO donator (L-аrginine) has shown a faster reaching the clinical effect on reducing endometriosis-associated symptoms and sustainable maintenance of the result achieved. The multifaceted pharmacological effects of L-arginine directly affect a number of essential factors for the adenomyosis development and progression, which allows using this drug in clinical practice.