Neurogenic inflammation: neuropeptides and nitric oxide synthase in patients with endometriosis and pelvic pain

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The predominant symptom for endometriosis is pain. The presence of nitrosative stress in the eutopic and ectopic endometrium may cause the pathological mechanism of pain through increased expression of neuropeptides. Objective — to evaluate the contribution of nitrosative stress in enhancing the expression of neuropeptides and the implementation of pain in patients with endometriosis. Material and methods. ELISA was used to determine the content of NOS, UCHL1, VIP in peritoneal fluid and in the blood; immunohistochemistry was used to assess the expression of nNOS, iNOS, VIP in vessels, UCHL1 and VIP densities; western blot was used to assess the expression of the protein nNOS, UBLH1, VIP; polymerase chain reaction was used to assess the expression of mRNA nNOS, mRNA UBLH1, mRNA VIP in eutopic and ectopic endometrium in patients with endometriosis and pelvic pain. Results. A comparative analysis of the content of NOS, UCHL1, VIP (ELISA, enzyme-linked immunosorbent assay) in the peritoneal fluid and in the blood; expression of nNOS and iNOS, VIP in vessels, density of UCHL1 and VIP (IHC, immunohistochemistry), expression of nNOS protein, UBLH1, VIP (WB, Westrn blot), expression of mRNA nNOS, mRNA UBLH1, mRNA VIP (PCR, polymerase chain reaction ) in eutopic and ectopic endometria in patients with endometriosis and pelvic pain a statistically significant increase in the studied parameters was shown. Conclusion. At the proteomic and transcriptomic levels, the role of nitrosative stress due to neuronal and inducible nitric oxide synthase has been proven to enhance the expression and accumulation of VIP and UCHL1 neuropeptides in eutopic and ectopic endometrium and in peritoneal fluid in patients with endometriosis and pelvic pain. The results can be used to assess the contribution of nitrosative stress in the implementation of pain in endometriosis and the choice of treatment tactics.

Keywords:

endometriosis

pain

ectopic endometrium

eutopic endometrium

nitrosative stress

neurogenesis

Authors:

Burlev V.A.

Nauchnyĭ tsentr akusherstva, ginekologii i perinatologii im. akad. V.I. Kulakova, Moskva

Il'iasova N.A.

Nauchnyĭ tsentr akusherstva, ginekologii i perinatologii im. akad. V.I. Kulakova, Moskva

List of references:

Ader R, Cohen N, Felten D. Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet. 1995;345(8942):99-103. https://doi.org/10.5555/uri:pii:S0140673695900667
Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflammation pathways: a general review. International Journal of Neuroscience. 2017;127(7):624-633. https://doi.org/10.1080/00207454.2016.1212854
Schain M, Kreisl WC. Neuroinflammation in Neurodegenerative Disorders-a Review. Current Neurology and Neuroscience Reports. 2017;17(3):25. https://doi.org/10.1007/s11910-017-0733-2
Frieri M. Neuroimmunology and inflammation: implications for therapy of allergic and autoimmune diseases. Annals of Allergy, Asthma and Immunology. 2003;90(6 Suppl 3):34-40. https://doi.org/10.1016/S1081-1206(10)61658-4
Tokushige N, Markham R, Russell P, Fraser IS. High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Human Reproduction. 2006;21:782-787. https://doi.org/10.1093/humrep/dei368
Burlev VA, Il’yasova NA. The density of nervous fiber and nucleus isoforms expression of estrogen and progesterone receptors in eutopic endometrium in patients with peritoneal endometriosis: pregnancy outcomes. Problemy reproduktsii. 2014;6:61-69. (In Russ.) https://doi.org/10.17116/repro201420661-69
Al-Jefout M, Dezarnaulds G, Cooper M, Tokushige N, Luscombe GM, Markham R, Fraser IS. Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study. Human Reproduction. 2009;24(12):3019-3024. https://doi.org/10.1093/humrep/dep275
Zevallos HB, McKinnon B, Tokushige N, Mueller MD, Fraser IS, Bersinger NA. Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and quantitative PCR in eutopic endometrium from women with and without endometriosis. Archives of Gynecology and Obstetrics. 2015;291(1):85-91. https://doi.org/10.1007/s00404-014-3379-1
Donnez O, Soares M, Defre`re S, Van Kerk O, Van Langendonckt A, Donnez J, Dolmans M-M, Colette S. Nerve fibers are absent in disease-free and eutopic endometrium, but present in endometriotic (especially deep) lesions. Journal of Endometriosis and Pelvic Pain Disorders. 2013;5:68-76. https://doi.org/10.5301/je.5000155
Newman TA, Bailey JL, Stocker LJ, Woo YL, Macklon NS, Cheong YC. Expression of neuronal markers in the endometrium of women with and those without endometriosis. Human Reproduction. 2013;28:2502-2510. https://doi.org/10.1093/humrep/det274
Bourlev V, Moberg C, Ilyasova N, Davey E, Kunovac Kallak T, Olovsson M. Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain. American Journal of Reproductive Immunology. 2018;80(3):e12857. https://doi.org/10.1111/aji.12857
Burlev VA, Il’iasova NA. Nitrosative stress in endometriosis. Problemy reproduktsii. 2019;25(3):16-24. (In Russ.) https://doi.org/10.17116/repro20192503116
Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertility and Sterility. 1997;67:817-821. https://doi.org/10.1016/S0015-0282(97)81391-X32
Bourlev V, Iljasova N, Adamyan L, Larsson A, Olovsson M. Signs of reduced angiogenic activity after surgical removal of deeply infiltrating endometriosis. Fertility and Sterility. 2010;94(1):52-57. https://doi.org/10.1016/j.fertnstert.2009.02.019
Bourlev V, Volkov N, Pavlovitch S, Lets N, Larsson A, Olovsson M. The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions. Reproduction. 2006;132(3):501-509. https://doi.org/10.1530/rep.1.01110
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T) Method. Methods. 2001;25(4):402-408. https://doi.org/10.1006/meth.2001.1262
Sorokin AV, Kim ER, Ovchinnikov LP. Proteasome system of protein degradation and processing. Uspekhi biologicheskoy khimii. 2009;49:3-76. (In Russ.)
Chaugule VK, Walden H. Specificity and disease in the ubiquitin system. Biochemical Society Transactions. 2016;44(part 1):212-227. https://doi.org/10.1042/BST20150209
Lv H, Wang Q, Wu S, Yang L, Ren P, Yang Y, Gao J, Li L. Neonatal hypoxic ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid. Clinica Chimica Acta. 2015;450:282-297. https://doi.org/10.1016/j.cca.2015.08.021
Singh GP, Nigam R, Tomar GS, Monisha M, Bhoi SK, S A, Sengar K, Akula D, Panta P, Anindya R. Early and rapid detection of UCHL1 in the serum of brain-trauma patients: a novel gold nanoparticle-based method for diagnosing the severity of brain injury. The Analyst. 2018;143(14):3366-3373. https://doi.org/10.1039/c8an00533h
Ren C, Kobeissy F, Alawieh A, Li N, Li N, Zibara K, Zoltewicz S, Guingab-Cagmat J, Larner SF, Ding Y, Hayes RL, Ji X, Mondello S. Assessment of serum UCH-L1 and GFAP in acute stroke patients. Scientific Reports. 2016;6:24588. https://doi.org/10.1038/srep24588
Matuszczak E, Tylicka M, Dębek W, Tokarzewicz A, Gorodkiewicz E, Hermanowicz A. Concentration of UHCL1 in the serum of children with acute appendicitis, before and after surgery, and its correlation with CRP and prealbumin. Journal of Investigative Surgery. 2018;31(2):136-141. https://doi.org/10.1080/08941939.2017.1282559
Matuszczak E, Tylicka M, Dębek W, Sankiewicz A, Gorodkiewicz E, Hermanowicz A. Overexpression of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in serum of children after thermal injury. Advances in Medical Sciences. 2017;62(1):83-86. https://doi.org/10.1016/j.advms.2016.07.004
Wang G, Zhang W, Zhou B, Jin C, Wang Z, Yang Y, Wang Z, Chen Y, Feng X. The diagnosis value of promoter methylation of UCHL1 in the serum for progression of gastric cancer. BioMed Research International. 2015;2015:741030. https://doi.org/10.1155/2015/741030
Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. The ubiquitin pathway in Parkinson’s disease. Nature. 1998;395(6701):451-452. https://doi.org/10.1038/26652
Burlev VA. Autoparacrine impairments of angiogenesis regulation in proliferative forms of female reproductive diseases. Akusherstvo i ginekologiya. 2006;3:34-40. (In Russ.)

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