{"paper_id":"08a580e8-dfcd-48fa-82d0-d10d22b369d1","body_text":"Abstract\nTo investigate the role of the nerve growth factor (NGF) in the development of dysmenorrhea/pelvic pain in patients with endometriosis, we performed a prospective, clinical, blind study. Peritoneal fluids (PFs) were obtained from patients with histologically proven endometriosis. Patients with endometriosis were divided into 7 different groups depending on their preoperative pain score and symptomatology: patients with no pain, patients with minimal pain (dysmenorrhea, pelvic pain, or both), and patients with severe pain (dysmenorrhea, pelvic pain, or both) and were used for the neuronal growth assay with cultured chicken dorsal root ganglia (DRG) and for Western blot analyses. Dorsal root ganglia were stained with anti-calcitonin gene-related peptide (CGRP) and anti-growth-associated protein 43 (GAP 43). Peritoneal fluids from patients with endometriosis induce neurite outgrowth. There was no significant difference in the outgrowth between the 7 pain groups. Western blot analyses showed a moderate NGF expression in the PFs from patients with endometriosis, without significant differences in the 7 pain groups. The present study suggests that the neurotrophic properties of endometriotic tissues are endometriosis- and not pain-associated.\nSimilar content being viewed by others\nReferences\nGiudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.\nBulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.\nTokushige N, Markham R, Russell P, Fraser IS. Nerve fibres in peritoneal endometriosis. Hum Reprod. 2006;21(11):3001–3007.\nMechsner S, Schwarz J, Thode J, Loddenkemper C, Salomon DS, Ebert AD. Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions. Fertil Steril. 2007;88(3):581–587.\nBerkley KJ, Dmitrieva N, Curtis KS, Papka RE. Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci USA. 2004;101(30):11094–11098.\nAnaf V, Simon P, El Nakadi I, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 2002;17(7):1895–1900.\nBarcena de Arellano ML, Arnold J, Vercellino F, Chiantera V, Schneider A, Mechsner S. Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions. Fertil Steril. 2011;95(3):1123–1126.\nRevised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.\nFinas D, Huszar M, Agic A, et al. L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis. Hum Reprod. 2008;23(5):1053–1062.\nAbdiche YN, Malashock DS, Pons J. Probing the binding mechanism and affinity of tanezumab, a recombinant humanized anti-NGF monoclonal antibody, using a repertoire of biosensors. Protein Sci. 2008;17(8):1326–1335.\nBokor A, Kyama CM, Vercruysse L, et al. Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis. Hum Reprod. 2009;24(12):3025–3032.\nAnaf V, Simon P, El Nakadi I, et al. Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod. 2000;15(8):1744–1750.\nZhang X, Yao H, Huang X, Lu B, Xu H, Zhou C. Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis. Hum Reprod. 2010;25(2):392–397.\nKaiser A, Kopf A, Gericke C, Bartley J, Mechsner S. The influence of peritoneal endometriotic lesions on the generation of endometriosis-related pain and pain reduction after surgical excision. Arch Gynecol Obstet. 2009;280(3):369–373.\nAtwal G, du Plessis D, Armstrong G, Slade R, Quinn M. Uterine innervation after hysterectomy for chronic pelvic pain with, and without, endometriosis. Am J Obstet Gynecol. 2005;193(5):1650–1655.\nQuinn M. Uterine innervation in adenomyosis. J Obstet Gynaecol. 2007;27(3):287–291.\nZhang X, Lu B, Huang X, Xu H, Zhou C, Lin J. Endometrial nerve fibers in women with endometriosis, adenomyosis, and uterine fibroids. Fertil Steril. 2009;92(5):1799–1801.\nVercellini P. Endometriosis: what a pain it is. Semin Reprod Endocrinol. 1997;15(3):251–261.\nDrake TS, O’Brien WF, Ramwell PW, Metz SA. Peritoneal fluid thromboxane B2 and 6-keto-prostaglandin F1 alpha in endometriosis. Am J Obstet Gynecol. 1981;140(4):401–404.\nVernon MW, Beard JS, Graves K, Wilson EA. Classification of endometriotic implants by morphologic appearance and capacity to synthesize prostaglandin F. Fertil Steril. 1986;46(5):801–806.\nMoon YS, Leung PC, Yuen BH, Gomel V. Prostaglandin F in human endometriotic tissue. Am J Obstet Gynecol. 1981;141(3):344–345.\nJones HJ. Endometriosis. Baltimore, MD: Williams & Wilkins; 1982.\nTran LV, Tokushige N, Berbic M, Markham R, Fraser IS. Macrophages and nerve fibres in peritoneal endometriosis. Hum Reprod. 2009;24(4):835–841.\nMantyh PW. Neurobiology of substance P and the NK1 receptor. J Clin Psychiatry. 2002;63(suppl 11):6–10.\nHaney AF, Muscato JJ, Weinberg JB. Peritoneal fluid cell populations in infertility patients. Fertil Steril. 1981;35(6):696–698.\nDunselman GA, Hendrix MG, Bouckaert PX, Evers JL. Functional aspects of peritoneal macrophages in endometriosis of women. J Reprod Fertil. 1988;82(2):707–710.\nKupker W, Schultze-Mosgau A, Diedrich K. Paracrine changes in the peritoneal environment of women with endometriosis. Hum Reprod Update. 1998;4(5):719–723.\nTsudo T, Harada T, Iwabe T, et al. Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues. Fertil Steril. 2000;73(2):205–211.\nHarada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76(1):1–10.\nYlikorkala O, Viinikka L. Prostaglandins and endometriosis. Acta Obstet Gynecol Scand Suppl. 1983;113:105–107.\nApfel SC. Neurotrophic factors and pain. Clin J Pain. 2000;16(2 suppl):S7–S11.\nSteinhoff M, Stander S, Seeliger S, Ansel JC, Schmelz M, Luger T. Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol. 2003;139(11):1479–1488.\nSchaible HG, Del Rosso A, Matucci-Cerinic M. Neurogenic aspects of inflammation. Rheum Dis Clin North Am. 2005;31(1):77–101, ix.\nRueff A, Mendell LM. Nerve growth factor NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro. J Neurophysiol. 1996;76(5):3593–3596.\nRueff A, Dawson AJ, Mendell LM. Characteristics of nerve growth factor induced hyperalgesia in adult rats: dependence on enhanced bradykinin-1 receptor activity but not neurokinin-1 receptor activation. Pain. 1996;66(2–3):359–372.\nVercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Fedele L. Chronic pelvic pain in women: etiology, pathogenesis and diagnostic approach. Gynecol Endocrinol. 2009;25(3):149–158.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nBarcena de Arellano, M.L., Arnold, J., Vercellino, G.F. et al. Influence of Nerve Growth Factor in Endometriosis-Associated Symptoms. Reprod. Sci. 18, 1202–1210 (2011). https://doi.org/10.1177/1933719111410711\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719111410711","source_license":"CC0","license_restricted":false}