β-Adrenoreceptors types 1 and 2 in the diagnosis of pain syndrome in patientswith various forms of adenomyosis

Close metadata

OBJECTIVE

Analysis of immunohistochemical expression of β1- and β2-adrenergic receptors (ADRB1 and ADRB2) in adenomyotic tissues in reproductive-age patients.

MATERIAL AND METHODS

The study included histological preparations and paraffin blocks from 30 patients with diffuse adenomyosis, 30 patients with nodular adenomyosis and 30 patients from the comparison group. Histological and immunohistochemical studies of excised adenomyosis tissue were performed in the 1st pathological anatomy department of the Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.

RESULTS

The study showed increased expression of β1- and β2-adrenergic receptors in adenomyosis foci compared to the control group, while a direct relationship was established when assessing the relationship between ADRB2 expression and ADRB1 expression. A direct relationship was also established between the severity of pain syndrome (assessed by the VAS scale) in patients with various forms of adenomyosis and the expression of β1- and β2-adrenergic receptors in the tissue of adenomyosis.

CONCLUSION

The data obtained by us allow us to objectify the severity of pain syndrome in patients with various forms of adenomyosis, since the level of expression of β1- and β2-adrenergic receptors positively correlates with the severity of pain syndrome. These findings make it possible to optimize the tactics of drug treatment of patients with adenomyosis and clarify the pathogenesis of pain syndrome in adenomyosis.

Keywords:

adenomyosis

pain syndrome

β-adrenergic receptors

Authors:

Adamyan L.V.

Russian Medical University;
Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology

SPIN RSCI: 9836-2713
Scopus AuthorID: 7006372422
ResearcherID: Q-1722-2018
ORCID: 0000-0002-3253-4512

Sokolov A.D.

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation

ORCID: 0000-0001-6558-0761

Arakelyan A.S.

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation

ORCID: 0000-0002-3217-1141

Badlaeva A.S.

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation

ORCID: 0000-0001-5223-9767

Asaturova A.V.

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation

ORCID: 0000-0001-8739-5209

Received:

01.02.2025

Accepted:

17.02.2025

List of references:

Vercellini P, Viganò P, Somigliana E, Daguati R, Abbiati A, Fedele L. Adenomyosis: epidemiological factors. Best Practice and Research Clinical Obstetrics and Gynaecology. 2006;20(4):465-477. https://doi.org/10.1016/j.bpobgyn.2006.01.017
Harada T, Khine YM, Kaponis A, Nikellis T, Decavalas G, Taniguchi F. The Impact of Adenomyosis on Women’s Fertility. Obstetrical and Gynecological Survey. 2016;71(9):557-568. https://doi.org/10.1097/OGX.0000000000000346
Adamyan LV, Sokolov AD, Avetisyan JuS, Shapovalenko RA. Methods of diagnostics of adenomyosis: a systematic review. Russian Journal of Human Reproduction. 2023;29(3):81-90. (In Russ.). https://doi.org/10.17116/repro20232903181
Smith SK. Prostaglandins and growth factors in the endometrium. Bailliere’s Clinical Obstetrics and Gynaecology. 1989;3(2):249-270. https://doi.org/10.1016/s0950-3552(89)80021-5
Struble J, Reid S, Bedaiwy MA. Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition. The Journal of Minimally Invasive Gynecology. 2016;23(2):164-185. https://doi.org/10.1016/j.jmig.2015.09.018
Huang FJ, Kung FT, Chang SY, Hsu TY. Effects of short-course buserelin therapy on adenomyosis. A report of two cases. The Journal of Reproductive Medicine. 1999;44(8):741-744.
Liu X, Shen M, Qi Q, Zhang H, Guo SW. Corroborating evidence for platelet-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis. Human Reproduction. 2016;31(4):734-749. https://doi.org/10.1093/humrep/dew018
Dzhamalutdinova KM, Kozachenko IF, Gus AI, Adamyan LV. Modern aspects of pathogenesis and diagnostics of adenomyosis. Akusherstvo i ginekologiya. 2018;1:29-34. (In Russ.). https://doi.org/10.18565/aig.2018.1.29-34
Shen M, Liu X, Zhang H, Guo SW. Transforming growth factor β1 signaling coincides with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the development of adenomyosis in mice. Human Reproduction. 2016;31(2):355-369. https://doi.org/10.1093/humrep/dev314
Zhang Q, Duan J, Liu X, Guo SW. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. Molecular and Cellular Endocrinology. 2016;428:1-16. https://doi.org/10.1016/j.mce.2016.03.015
Guo SW. Fibrogenesis resulting from cyclic bleeding: the Holy Grail of the natural history of ectopic endometrium. Human Reproduction. 2018;33(3):353-356. https://doi.org/10.1093/humrep/dey015
Marjoribanks J, Proctor ML, Farquhar C. Nonsteroidal anti-inflammatory drugs for primary dysmenorrhoea. The Cochrane Database of Systematic Reviews. 2003;(4):CD001751. https://doi.org/10.1002/14651858.CD001751
Etrusco A, Barra F, Chiantera V, Ferrero S, Bogliolo S, Evangelisti G, Oral E, Pastore M, Izzotti A, Venezia R, Ceccaroni M, Laganà AS. Current Medical Therapy for Adenomyosis: From Bench to Bedside. Drugs. 2023;83(17):1595-1611. https://doi.org/10.1007/s40265-023-01957-7
Orazov MR, Chaika AV, Nosenko EN. Possibilities of non-hormonal pathogenetic treatment of chronic pelvic pain in women with adenomyosis. Mediko-social`ny`e problemy` sem`i. 2013;1:33-37. (In Russ.).
Zairat’yants OV, Andreeva EN, Adamyan LV, Sonova MM, Urumova LT, Bolotnikov AI, Ilyichev AV, Maldov DG. Endometriosis: new experience of non-hormonal treatment. Russian Journal of Human Reproduction. 2018;24(6):113-120. (In Russ.). https://doi.org/10.17116/repro201824061113
Vannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo SW, Petraglia F. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reproductive Biomedicine Online. 2017;35(5):592-601. https://doi.org/10.1016/j.rbmo.2017.06.016
Shklyar AA, Adamyan LV, Kogan EA, Paramonova NB, Kozachenko IPh, Gavrilova TYu. The clinical and morphological features of nodular and diffuse forms of adenomyosis. Russian Journal of Human Reproduction. 2015;21(1):74-79. (In Russ.). https://doi.org/10.17116/repro20152174-79
Guo SW, Mao X, Ma Q, Liu X. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertility and Sterility. 2013;99(1):231-240. https://doi.org/10.1016/j.fertnstert.2012.08.038
Nie J, Liu X, Guo SW. Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis. American Journal Of Obstetrics and Gynecology. 2010;202(4):346.e1-346.e3468. https://doi.org/10.1016/j.ajog.2009.11.035
Brainard AM, Korovkina VP, England SK. Potassium channels and uterine function. Seminars in Cell and Developmental Biology. 2007;18(3):332-339. https://doi.org/10.1016/j.semcdb.2007.05.008
Mechsner S, Grum B, Gericke C, Loddenkemper C, Dudenhausen JW, Ebert AD. Possible roles of oxytocin receptor and vasopressin-1α receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri. Fertility and Sterility. 2010;94(7):2541-2546. https://doi.org/10.1016/j.fertnstert.2010.03.015
Shi H, Li R, Qiang J, Li Y, Wang L, Sun R. Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model. PloS One. 2016;11(7):e0160102. https://doi.org/10.1371/journal.pone.0160102
Krantz KE. Innervation of the human uterus. Annals of the New York Academy of Sciences. 1959;75:770-784. https://doi.org/10.1111/j.1749-6632.1959.tb44589.x
Carrarelli P, Luddi A, Funghi L, Arcuri F, Batteux F, Dela Cruz C, Tosti C, Reis FM, Chapron C, Petraglia F. Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions. Reproductive Biomedicine Online. 2016;33(4):476-483. https://doi.org/10.1016/j.rbmo.2016.07.009
Cheretsova AS, Adamyan LV, Sharov MN, Murvatov KD, Kiselev SI, Yarotskaya EL, Prokofieva YuS. Objectification of chronic pelvic pain in patients with endometriosis. Russian Journal of Human Reproduction. 2023;29(6):102-105. (In Russ.). https://doi.org/10.17116/repro202329061102
Apfel SC. Neurotrophic factors and pain. The Clinical Journal of Pain. 2000;16(2 Suppl):S7-S11. https://doi.org/10.1097/00002508-200006001-00003
Zhang X, Lu B, Huang X, Xu H, Zhou C, Lin J. Endometrial nerve fibers in women with endometriosis, adenomyosis, and uterine fibroids. Fertility and Sterility. 2009;92(5):1799-1801. https://doi.org/10.1016/j.fertnstert.2009.05.016
Zhang X, Lu B, Huang X, Xu H, Zhou C, Lin J. Innervation of endometrium and myometrium in women with painful adenomyosis and uterine fibroids. Fertility and Sterility. 2010;94(2):730-737. https://doi.org/10.1016/j.fertnstert.2009.03.026
Choi YJ, Chang JA, Kim YA, Chang SH, Chun KC, Koh JW. Innervation in women with uterine myoma and adenomyosis. Obstetrics and Gynecology Science. 2015;58(2):150-156. https://doi.org/10.5468/ogs.2015.58.2.150
Li Y, Zhang SF, Zou SE, Xia X, Bao L. Accumulation of nerve growth factor and its receptors in the uterus and dorsal root ganglia in a mouse model of adenomyosis. Reproductive Biology and Endocrinology: RB&E. 2011;9:30. https://doi.org/10.1186/1477-7827-9-30
Chen Y, Zhu B, Zhang H, Liu X, Guo SW. Epigallocatechin-3-gallate reduces myometrial infiltration, uterine hyperactivity, and stress levels and alleviates generalized hyperalgesia in mice induced with adenomyosis. Reproductive Sciences. 2013;20(12):1478-1491. https://doi.org/10.1177/1933719113488455
Adamyan LV, Murvatov KD, Obelchak IS, Chernetsova AS, Zherebuov AI, Mareev AV. Modern aspects of diagnostics and treatment of chronic pelvic pain in gynecology. Vestnik medicinskogo instituta neprery`vnogo obrazovaniya. 2023;4:93-98. (In Russ.).
Wang F, Shi X, Qin X, Wen Z, Zhao X, Li C. Expression of CD56 in patients with adenomyosis and its correlation with dysmenorrhea. European journal of obstetrics, gynecology, and reproductive biology. 2015;194:101-105. https://doi.org/10.1016/j.ejogrb.2015.08.027
Nie J, Liu X, Zheng Y, Geng JG, Guo SW. Increased immunoreactivity to SLIT/ROBO1 and its correlation with severity of dysmenorrhea in adenomyosis. Fertility and Sterility. 2011;95(3):1164-1167. https://doi.org/10.1016/j.fertnstert.2010.09.027
Chen Y, Li D, Zhang Z, Takushige N, Kong BH, Wang GY. Effect of siRNA against β-NGF on nerve fibers of a rat model with endometriosis. Reproductive Sciences. 2014;21(3):329-339. https://doi.org/10.1177/1933719113497279
Lertvikool S, Sukprasert M, Pansrikaew P, Rattanasiri S, Weerakiet S. Comparative study of nerve fiber density between adenomyosis patients with moderate to severe pain and mild pain. Journal of the Medical Association of Thailand. 2014;97(8):791-797.
Xu X, Cai X, Liu X, Guo SW. Possible involvement of neuropeptide and neurotransmitter receptors in Adenomyosis. Reproductive Biology and Endocrinology: RB&E. 2021;19(1):25. https://doi.org/10.1186/s12958-021-00711-6
Remmele W, Stegner HE. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Der Pathologe.1987;8(3):138-140.
Jana B, Całka J. Effect of blocking of alpha1-adrenoreceptor isoforms on the noradrenaline-induced changes in contractility of inflamed pig uterus. PloS One. 2023;18(2):e0280152. https://doi.org/10.1371/journal.pone.0280152
Long Q, Liu X, Qi Q, Guo SW. Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2. Human Reproduction. 2016;31(11):2506-2519. https://doi.org/10.1093/humrep/dew237
Jana B, Całka J, Andronowska A, Mówińska A, Witek K, Palus K. Noradrenaline and Adrenoreceptors are Involved in the Regulation of Prostaglandin I2 Production in the Porcine Endometrium after Experimentally Induced Inflammation. International Journal of Molecular Sciences. 2024;25(12):6313. https://doi.org/10.3390/ijms25126313
Zhang X, Hartung JE, Bortsov AV, Kim S, O’Buckley SC, Kozlowski J, Nackley AG. Sustained stimulation of β2- and β3-adrenergic receptors leads to persistent functional pain and neuroinflammation. Brain, Behavior, and Immunity. 2018;73:520-532. https://doi.org/10.1016/j.bbi.2018.06.017

Close metadata