{"paper_id":"ecdc13b0-8cea-4281-9fd0-72f344e48032","body_text":"МЕДИЦИНСКИЙ ВЕСТНИК СЕВЕРНОГО КАВКАЗА \n2016. Т. 11. № 2\nMedical news of north caucasus\n2016. Vоl. 11. iss. 2\n189189189189\nexplants by inflammatory mediators. J Soc Gynecol In-\nvestig 2000;7(5):291-296.\n18. Segerer S. E., M üller N., van den Brandt J., Kapp M., \nDietl J., Reichardt H. M. et al. The glycoprotein-hor-\nmones activin A and inhibin A interfere with dendritic cell \nmaturation. Reproductive Biology and Endocrinology. \n2008;6:17.\n19. Zygmunt M., Herr F ., Munstedt K., Lang U., Liang O. D. \nAngiogenesis and vasculogenesis in pregnancy. Eur J \nObstet Gynecol Reprod Biol. 2003;110:S10-S18.\n20. Zhang E. G., Smith S. K., Baker P . N., Char-\nnock-Jones D. S. The regulation and localization of an-\ngiopoietin-1, -2, and their receptor Tie2 in normal and \npathologic human placentae. Mol Med. 2001;7:624-635.\n21. Plaiser M., Dennert I., Rost E., Koolwijk P ., van Hins-  \nbergh V . W. et al. Decidual vascularization and the ex-\npression of angiogenic growth factors and proteases in \nfirst trimester spontaneous abortions. Human reproduc-\ntion. 2009;24:1:185-197.\n22. Gravanis A., Margioris A. N. The corticotropin-releasing \nfactor (CRF) family of neuropeptides in inflammation: \npotential therapeutic applications. Curr Med Chem.  \n2005;12:1503-1512.\n23. Kalantaridou S. N., Makrigiannakis A., Zoumakis E., \nChrousos G. P . Stress and the female reproductive sys-\ntem. J Reprod Immunol. 2004;62:61-68.\n24. Makrigiannakis A., Zoumakis E., Kalantaridou S., Couti-\nfaris C., Margioris A. N. et al. Corticotropin-releasing \nhormone promotes blastocyst implantation and early \nmaternal tolerance. Nat Immunol. 2001;2:1018-1024.\n25. Bamberger C. M., Minas V ., Bamberger A. M., Charalam-\npopoulos I., Fragouli Y . et al. Expression of urocortin in \nthe extravillous human trophoblast at the implantation \nsite. Placenta. 2007;28:127-132.\nabout\tauthors:\nDubrovina Svetlana, MD, PhD, Professor, main researcher;  \ntel.: +7(863)2504200; e-mail: s.dubrovina@gmail.com\nMakluk Aliya, MD, gynecologist of Scientific Research Institute  \nof Obstetrics and Pediatrics» of Ministry of Health of Russian Federation;  \ntel.: +7(863)2993542; e-mail: secretary@rniiap.ru\nGimbut Vitaliy, MD, gynecologist of Scientific Research Institute; \ntel.: +7(863)2993542; e-mail: secretary@rniiap.ru\nKrasilnikova Liliya, MD, postgraduated student;  \ntel.: +7(863)2504200; e-mail: cool.dalida2014@yandex.ru\n© Group of authors, 2016\nUDC 618.14-002:616.718.19\nDOI – http://dx.doi.org/10.14300/mnnc.2016.11033\nISSN – 2073-8137\npeculiariTies\tof\tThe\tDeVelopmenT\tof\tchronic\tpelVic\t  \npain\trelaTeD\tcomponenTs\tin\tperiToneal\tenDomeTriosis\nKutsenko\ti.\ti.,\tKravtsova\te.\ti.,\tmusolyants\tr.\ta.,\tnazarenko\te.\ti.\nKuban\tstate\tmedical\tuniversity,\tKrasnodar,\trussian\tfederation\nОСОБЕННОСТИ\tФОРМИРОВАНИЯ\tКОМПОНЕНТОВ\tХРОНИчЕСКОй\t  \nТАзОВОй\tБОЛИ\tПРИ\tПЕРИТОНЕАЛЬНОМ\tЭНДОМЕТРИОзЕ\t\nИ.\tИ.\tКуценко,\tЕ.\tИ.\tКравцова,\tР.\tА.\tМусольянц,\tЕ.\tИ.\tНазаренко\nКубанский\tгосударственный\tмедицинский\tуниверситет,\tКраснодар,\t \nРоссийская\tФедерация\nThe article includes the results of the complex study of cytokine and serotonin status as pathogenic chronic \npelvic pain related factors in peritoneal endometriosis. The distinctive features of the development of the syndrome \nassociated with the severity and character of the pelvic pain due to peritoneal endometriosis have been revealed. \nKey words: chronic pelvic pain, peritoneal endometriosis, cytokines, serotonin\nПредставлены результаты комплексного исследования цитокинового и серотонинового статусов как фак-\nторов, участвующих в формировании патогенетических компонентов хронической тазовой боли при перито-\nнеальном эндометриозе. Выявлены особенности формирования данного синдрома в зависимости от интен-\nсивности и характера течения тазовой боли при перитонеальном эндометриозе. \nКлючевые слова: хроническая тазовая боль, перитонеальный эндометриоз, цитокины, серотонин\n\n190190190\noriginal  research\n obstetriсs  and  gynecology\nОригинальные  исследОвания\nАкушерство и гинекология190\nE\nndometriosis is one of the most common \ngynecologic disorders and is found in \napproximately 70 % of patients with chronic \npelvic pain [1]. Approximately 25 % of women with \npelvic pain were diagnosed peritoneal endometriosis \nby laparoscopy. Numerous investigations of \ndifferent aspects of chronic pain due to peritoneal \nendometriosis were performed but none of the \ndeveloped methods resulted in complete regression \nof chronic pelvic pain or allowed avoiding recurrence \nof the disease [3, 4]. This can be referred to a complex \nstructure of the chronic pain which is heterogeneous \nin nature as a rule and is presented as a combination of \nsymptomatic complex, demonstrating the presence \nof nociceptive, nuerogenic and psychogenic \nconstituents [2, 5]. Though different chronic pain \nrelated factors in peritoneal endometriosis have \nbeen studied. C omplex studies of its pathogenic \ncomponents, especially in different bodily pain and \ncharacter of pain syndrome are not still available. \nAt the same time registration of these pathogenic \npeculiarities allows developing more effective \nmedical suppression for different stages of chronic \npelvic pain due to peritoneal endometriosis.\nThe aim of the study was to assess the peculiarities \nof the cytokine and serotonin status as factors providing \nformation of the components of chronic pelvic pain \ncaused by peritoneal endometriosis of different intensity \nand character of the painful syndrome.\nMaterial and Methods. We studied 195 female \npatients with chronic pelvic pain due to peritoneal \nendometriosis and 30 practically healthy women (control \ngroup) between 25–42 years of age. The groups were \ncomparable regarding the main indexes. Laparoscopy \nperformed for pelvic pain syndrome revealed stage II \nand III peritoneal endometriosis in all the patients. The \ndata were confirmed by histological examination. 109 \n(55.9 %) patients were diagnosed primary peritoneal \nendometriosis, 86 (44.1 %) had the recurrent pelvic \npains due to peritoneal endometriosis. \nThe severity of pain was determined by \nvisual analog scale (VAS).\nAccording to the severity of \ndiagnosed pain syndrome and according \nto the character of the disease (primary \nor recurrent) the patients were divided \ninto four clinical groups. The patients of \nthe group 1 (n=53, VAS 4–6 grades) and \nthe group 2 (n=56, VAS 7–10 grades) \nwere revealed primary peritoneal \nendometriosis. The patients of the \ngroup 3 (n=45, VAS 4–6 grades) and \nthe group 4 (n=41, VAS 7–10 grades) \ndemonstrated recurrent chronic pelvic \npain. The fifth group was a control \none (n=30). All patients underwent \ncomplex clinical studies of their cytokine \nprofile, serotonin antinociceptive \nneurotransmitter in the peripheral blood \nas well as their psychic and emotional \nstatus using Spilburg – Hanin tests and \nquestionnaire SF-36.\nThe statistical processing was \ncarried out using the descriptive statistics. The difference \nof central parameters was made using the criterion of \nMann – Whitney or there was applied the criterion χ\n2 \nto compare  the frequencies. There was used the add-\nin in the program EXCEL «Analysis package» and the \nstatistical program package STATISTICA V .8 as well as. \nThe differences at р<0.05 were authentic. \nResults and Discussion. Among the patients with \nthe primary peritoneal endometriosis the cases with \nchronic pelvic pain of 1–2 year duration were the most \ncommon and accounted for 63.3 %. The high incidence of \nrecurrent peritoneal endometriosis was revealed among \nthe patients with 3–5 year (52.3 %) and 6–8 year (47.7 %) \nduration of this syndrome. Besides chronic pelvic pain \n57 (29.2 %) patients were revealed dysmenorrhea and \n30 (15.4 %) demonstrated dyspareunia. All patients had \nsuch emotional disturbances as sleeplessness, fatigue, \nchangeable mood, irritability, emotional instability, \nanxiety, phobias, and others. Our studies didn’t reveal \nany association of marked chronic pelvic pain with the \nstage of the peritoneal endometriosis, its location, the \ntype of heterotopias, as well as the character of the \ndisease (primary or recurrent). \nSumming up the data on the changes of cytokine \nforce in peripheral blood it is possible to suggest the \npresence of inflammatory component in the pathogenesis \nof chronic pelvic pain of different severity and character \n(Fig. 1). At the same time the patients with primary disease \ndemonstrated statistically significant increase (p<0.05) \nof anti-inflammatory interleukin concentration when the \npain got worse (group 1 and 2). It was compensated to a \ngreat extend by the turn of anti-inflammatory force with \ndelayed increase. It shows the anti-inflammatory index \nthat represents the correlation in the interleukin-1β family. \nIn case of mild recurrent chronic pelvic pain maximum \npermissible domination of inflammatory cytokine level \n(p<0.05) and some inhibition of anti-inflammatory level was \nrevealed in the peripheral blood of patients with peritoneal \nendometriosis of various stages. These data have been \nconfirmed by anti-inflammatory index. The fourth group \nof patients with recurrent severe pelvic pain demonstrated \nstatistically significant depression of pro- and anti-\ninflammatory cytokine force (p<0.05) with the decrease in \nabsolute index of interleukin level that indicates «the false \nstabilization» determined by anti-inflammatory index and \nis the evidence of failure in adaptive capacity as well. \nIn all groups of patients the level of serotonin in \nperipheral blood was reduced as compared with the \ncontrol group (p<0.05). In spite of the fact that the \npatients considered their pain as mild it should be \nmentioned that the serotonin level in patients of the third \nclinical group with median 150.1±1.8 ȵg/ml as well as in \nthe patients of the first group with median 164.0±1.2 ȵg/\nFig. 1. Cytokine status in patients with various chronic  \npelvic pains due to peritoneal endometriosis\n\n\nМЕДИЦИНСКИЙ ВЕСТНИК СЕВЕРНОГО КАВКАЗА \n2016. Т. 11. № 2\nMedical news of north caucasus\n2016. Vоl. 11. iss. 2\n191191191191\nml (p<0.05). was reliably different. The \nmean level of serotonin in the peripheral \nblood of patients in the second and \nfourth groups was 110.41±1.4 ȵ g/ml, \nMe – 109 and 96.1±1.7 ȵg/ml, Me – 95, \nrespectively. The level of serotonin in \ngroups 2 and 4 was significantly low as \ncompared with the clinical groups 1 and \n3 (p<0.05). At the same time the quantity \nof serotonin in patients of the group 4 \nwas reliably lower (p<0.05) than in group \n2. However according to VAS the pain in \nthese groups was objectively identical \n(7.7±0.1 and 7.7±0.1 respectively). \nOur studies have demonstrated the \nimpairment of serotonin status as the \nindex of pain intensity in all the patients \nwith chronic pelvic pain. The reduction \nof serotonin level worsened in pain \nreinforcement. In recurrent identical \npains serotonin synthesis is significantly \ndepressed. This is associated with \ncytokine misbalance and can be the \nevidence of analgetic system depletion \nand development of psychogenic component of pain \nsyndrome in recurrent chronic pelvic pain due to \nperitoneal endometriosis.\nThe dynamic of the psychic and emotional status \nimpairment was identical. The levels of reactionary and \npersonal anxiety, as well as the quality of life assessment \ndepend on the pain syndrome severity; but these indices \nwere noted to be significantly low in group 3 and 4 with \nrecurrent chronic pelvic pain (p<0.05) that is in chronic \npersistent pain syndrome. It should be mentioned that \npsychosomatic disorders are closely associated with \ncytokine and serotonin status (Fig. 2). \nConclusions. Our studies have demonstrated that in \npain syndrome caused by peritoneal endometriosis in-\ntractable immune inflammation initiating chronic inflam-\nmatory process leads to persistent painful symptoms \nand promotes prolonged hyperexcitability of nociceptive \nsystem that causes serotonin level reduction. At the same \ntime in the patients with recurrent chronic pelvic pain due \nto peritoneal endometriosis the disease was found to \nhave a reliably long course with aggravated nociceptible, \nneurogenic and psychogenic pain related components. \n«Relation» of chronic pain and psychoemotional disor-\nders can be referred to general pathogenic mechanisms \nas well as to the failure of the neurotransmitter exchange \nin the central nervous system. It is serotonin that controls \nsuch function of the transmitter system of the brain as: \nopiate, dopaminergic, and adrenoceptive. Insufficiency \nof serotonin energetic system of the brain is evident both \nin chronic pelvic pain and in psychosomatic disorders. \nThus the study of the chronic pelvic pain related factors \nin primary peritoneal endometriosis is characterized by \nsuch distinctive features as intensification of nocicepti-\nble and neuropathic pain related components depend-\ning on the bodily pain. However , only marked duration of \nthe pain syndrome (recurrence) results in development \nof dominant psychogenic pain related component that is \nmedically resistent.\nReferences\n1.  Adamyan L. V . Endometriosis: Diagnoses, Management \nand Rehabilitation. Federal clinical recommendation for \ntreatment. Moscow; 2013. 86 р.\n2.  Chernuha G. E. Chronic pelvic pain: exciting cause and \ncomplications. Problems of reproduction. 2011;5:83-89.\n3.  Gormsen L., Jensen T . S., Bach F . W., Rosenberg R. Pain \nand depression. Ugeskr Laeger. 2012;168(20):1967-1999.\n4.  Flor H., Turk D. C. Chronic pain: An Integrated Biobeha-  \nvioral Approach. London: Informa Healthcare Publishing \nGroup. 2011.\n5.  Leonard B. Clinical implications of mechanisms of action \nof antidepressants. Advances in Psychiatric Treatment. \n2012;6:178-186.\nabout\tauthors:\nKutsenko Irina, DM, PhD, Head of Chair of Obstetrics, Gynecology and Perinatology;  \ntel.: +79882420460; e-mail: iikucenko@mail.ru\nKravtsova Elena, PhD, Associate Professor of Chair of Obstetrics, Gynecology and Perinatology;  \ntel.: +79183915973; e-mail: luzum69@mail.ru\nMusolyants Rusanna, Post-graduate student of Chair of Obstetrics, Gynecology and Perinatology;  \ntel.: +79189357729; e-mail: musolyants87@mail.ru\nNasarenko Elena, PhD, Associate Professor of Chair of Obstetrics, Gynecology and Perinatology;  \ntel.: +79882454518; e-mail: elenanazarenko_kgmu@mail.ru\nFig. 2. Correlation of serotonin level index in peripheral blood with severity  \nof pelvic pains and proinflammatory index in various chronic pelvic pains due  \nto peritoneal endometriosis","source_license":"CC0","license_restricted":false}