{"paper_id":"abd2034a-378c-452e-b62b-29c27b80e684","body_text":"Summary\nEndometriosis-associated pain (EAP) is a major health concern in women of reproductive age. Due to the limited knowledge in the etiology and mechanisms of EAP, current treatment options remain deficient. In this chapter, we review the potential mechanisms contributing to EAP in the roles of neuroinflammation, neurogenesis and neural sensitization, as well as current clinical and pre-clinical treatments for EAP. Also the current knowledge and interrelationship between EAP and psychological well-being for the EAP treatment are discussed. Potential of individualized, multisubject care, integrating medical and psychological management for EAP are appraised.\nInflammation, peripheral and central pain generators, endocrine changes and structural alterations in the periphery and in the central nerve system may all contribute to endometriosis-associated pain. Psychological aspects of endometriosis-associated pain similarly evolve, with changes in mood and acceptance over the course of the disease.\n—Christian M. Becker\nAccess this chapter\nTax calculation will be finalised at checkout\nPurchases are for personal use only\nSimilar content being viewed by others\nAbbreviations\n- ACOG:\n-\nAmerican College of Obstetricians and Gynecologists\n- ASRM:\n-\nAmerican Society for Reproductive Medicine\n- BDNF:\n-\nBrain-derived neurotrophic factor\n- CBT:\n-\nCognitive behavioral therapy\n- CCL5:\n-\nC–C motif chemokine ligand 5\n- CGRP:\n-\nCalcitonin gene-related peptide\n- CHM:\n-\nChinese herbal medicine\n- CNS:\n-\nCentral nerve system\n- COC:\n-\nCombined oral contraceptive\n- COX:\n-\nCyclo-oxygenase\n- CPP:\n-\nChronic pelvic pain\n- DIE:\n-\nDeep infiltrating endometriosis\n- DIM:\n-\n3,3′-Diindolylmethane\n- DRG:\n-\nDorsal root ganglia\n- EGCG:\n-\nEpigallocatechin-3-gallate\n- ENA-78:\n-\nEpithelial neutrophil activating peptide-78\n- ER:\n-\nEstrogen receptor\n- ESHRE:\n-\nEuropean Society of Human Reproduction and Embryology\n- FKN:\n-\nFractalkine\n- GAP-43:\n-\nGrowth-associated protein 43\n- GnRH-a:\n-\nGonadotropin-releasing hormone agonist\n- HPA:\n-\nHypothalamic–pituitary–adrenal\n- IBD:\n-\nInflammatory bowel disease\n- IFN:\n-\nInterferon\n- IL:\n-\nInterleukin\n- LNG-IUD:\n-\nLevonorgestrel-releasing intrauterine device\n- LUNA:\n-\nLaparoscopic uterosacral nerve ablation\n- MAPK:\n-\nMitogen-activated protein kinase\n- MC:\n-\nMast cell\n- MCP1:\n-\nMonocyte chemoattractant protein 1\n- NGF:\n-\nNerve growth factor\n- NO:\n-\nNitric oxide\n- NSAID:\n-\nNon-steroid anti-inflammatory drug\n- NT:\n-\nNeurotrophin\n- PF:\n-\nPeritoneal fluid\n- PG:\n-\nProstaglandin\n- PMB:\n-\nPsychological and mind–body\n- PMR:\n-\nProgressive muscle relaxation\n- PNS:\n-\nPeripheral nerve system\n- PSN:\n-\nPresacral neurectomy\n- QoL:\n-\nQuality of life\n- RA:\n-\nRheumatoid arthritis\n- RANTES:\n-\nRegulated on activation, normal T cell expressed and secreted\n- RCT:\n-\nRandomized control trial\n- ROS:\n-\nReactive oxygen species\n- RVM:\n-\nRostral ventromedial medulla\n- SCNA:\n-\nSodium channel\n- SERM selective estrogen:\n-\nReceptor modulator\n- SNM:\n-\nSacral neuromodulation\n- SP:\n-\nSubstance P\n- SPRM selective progesterone:\n-\nReceptor modulator\n- TGF:\n-\nTransforming growth factor\n- TNF:\n-\nTumor necrosis factor\n- TrkB:\n-\nTyrosine kinase type B\n- TRPA1:\n-\nTransient receptor potential ankyrin 1\n- TRPV1:\n-\nTransient receptor potential vanilloid 1\n- VEGF:\n-\nVascular endothelial growth factor\n- WES:\n-\nWorld Endometriosis Society\nReferences\nZondervan KT, Becker CM, Missmer SA (2020) Endometriosis. N Engl J Med 382(13):1244–1256\nWang Y, Nicholes K, Shih IM (2020) The origin and pathogenesis of endometriosis. Annu Rev Pathol 15:71–95\nJohnson NP, Hummelshoj L et al (2013) World Endometriosis Society Montpellier, consensus on current management of endometriosis. Hum Reprod 28(6):1552–68\nFacchin F et al (2019) Preliminary insights on the relation between endometriosis, pelvic pain, and employment. Gynecol Obstet Invest 84(2):190–195\nBallard KD et al (2008) Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study–Part 1. BJOG 115(11):1382–1391\nShakiba K et al (2008) Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol 111(6):1285–1292\nAbbott J et al (2004) Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril 82(4):878–884\nSurrey ES et al (2018) Risk of developing comorbidities among women with endometriosis: a retrospective matched Cohort study. J Womens Health (Larchmt) 27(9):1114–1123\nProctor M, Farquhar C (2006) Diagnosis and management of dysmenorrhoea. BMJ 332(7550):1134–1138\nFall M et al (2010) EAU guidelines on chronic pelvic pain. Eur Urol 57(1):35–48\nLatthe P et al (2006) WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health 6:177\nFlor H (2002) Painful memories. Can we train chronic pain patients to ‘forget’ their pain? EMBO Rep 3(4):288–91\nBall E, Khan KS (2020) Recent advances in understanding and managing chronic pelvic pain in women with special consideration to endometriosis. F1000Res 9\nFerrero S et al (2005) Quality of sex life in women with endometriosis and deep dyspareunia. Fertil Steril 83(3):573–579\nYong PJ (2017) Deep dyspareunia in endometriosis: a proposed framework based on pain mechanisms and Genito-Pelvic pain penetration disorder. Sex Med Rev 5(4):495–507\nDrabble SJ et al (2021) Constellations of pain: a qualitative study of the complexity of women’s endometriosis-related pain. Br J Pain 15(3):345–356\nSeracchioli R et al (2008) Dyschezia and posterior deep infiltrating endometriosis: analysis of 360 cases. J Minim Invasive Gynecol 15(6):695–699\nNicolaus K et al (2020) Cycle-related diarrhea and dysmenorrhea are independent predictors of peritoneal endometriosis, cycle-related dyschezia is an independent predictor of rectal involvement. Geburtshilfe Frauenheilkd 80(3):307–315\nFacchin F et al (2015) Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference. J Psychosom Obstet Gynaecol 36(4):135–141\nCramer DW et al (1986) The relation of endometriosis to menstrual characteristics, smoking, and exercise. JAMA 255(14):1904–1908\nMahmood TA et al (1991) Menstrual symptoms in women with pelvic endometriosis. Br J Obstet Gynaecol 98(6):558–563\nConroy I et al (2021) Pelvic pain: what are the symptoms and predictors for surgery, endometriosis and endometriosis severity. Aust N Z J Obstet Gynaecol 61(5):765–772\nEvans S et al (2021) Phenotypes of women with and without endometriosis and relationship with functional pain disability. Pain Med 22(7):1511–1521\nEvans SF et al (2018) The comorbidities of dysmenorrhea: a clinical survey comparing symptom profile in women with and without endometriosis. J Pain Res 11:3181–3194\nFauconnier A, Chapron C (2005) Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update 11(6):595–606\nPerello MF et al (2017) Endometriotic pain is associated with adenomyosis but not with the compartments affected by deep infiltrating endometriosis. Gynecol Obstet Invest 82(3):240–246\nDemco L (1998) Mapping the source and character of pain due to endometriosis by patient-assisted laparoscopy. J Am Assoc Gynecol Laparosc 5(3):241–245\nMuzii L et al (1997) Correlation between endometriosis-associated dysmenorrhea and the presence of typical or atypical lesions. Fertil Steril 68(1):19–22\nFedele L et al (1992) Pain symptoms associated with endometriosis. Obstet Gynecol 79(5(Pt 1)):767–9\nVercellini P et al (2007) Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod 22(1):266–271\nDunselman GA et al (2014) ESHRE guideline: management of women with endometriosis. Hum Reprod 29(3):400–412\nDai Y et al (2012) Anatomical distribution of pelvic deep infiltrating endometriosis and its relationship with pain symptoms. Chin Med J (Engl) 125(2):209–213\nZheng YM et al (2020) Incidence of deeply infiltrating endometriosis among 240 cases of pelvic endometriosis and analysis of its clinical and pathological characteristics. Zhonghua Fu Chan Ke Za Zhi 55(6):384–389\nChapron C et al (2012) Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis. Hum Reprod 27(3):702–711\nMontanari E et al (2019) Association between disease extent and pain symptoms in patients with deep infiltrating endometriosis. Reprod Biomed Online 39(5):845–851\nChapron C et al (2003) Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease. Hum Reprod 18(4):760–766\nFauconnier A et al (2002) Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil Steril 78(4):719–726\nShafrir AL et al (2018) Risk for and consequences of endometriosis: a critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol 51:1–15\nDai Y et al (2019) Not having been breastfed may protect Chinese women from developing deep infiltrating endometriosis: results from subgroup analyses of the FEELING study. Reprod Sci 26(8):1158–1167\nMalfliet A et al (2021) Obesity hurts: the why and how of integrating weight reduction with chronic pain management. Phys Ther 101(11)\nFerries-Rowe E, Corey E, Archer JS (2020) Primary dysmenorrhea: diagnosis and therapy. Obstet Gynecol 136(5):1047–1058\nRicci E et al (2016) Physical activity and endometriosis risk in women with infertility or pain: systematic review and meta-analysis. Medicine (Baltimore) 95(40):e4957\nHansen S, Sverrisdottir UA, Rudnicki M (2021) Impact of exercise on pain perception in women with endometriosis: a systematic review. Acta Obstet Gynecol Scand 100(9):1595–1601\nQi X et al (2021) Relationship between dairy products intake and risk of endometriosis: a systematic review and dose-response meta-analysis. Front Nutr 8:701860\nVennberg Karlsson J, Patel H, Premberg A (2020) Experiences of health after dietary changes in endometriosis: a qualitative interview study. BMJ Open 10(2):e032321\nBravi F et al (2014) Tobacco smoking and risk of endometriosis: a systematic review and meta-analysis. BMJ Open 4(12):e006325\nNirgianakis K et al (2022) Effectiveness of dietary interventions in the treatment of endometriosis: a systematic review. Reprod Sci 29(1):26–42\nHoward FM (2009) Endometriosis and mechanisms of pelvic pain. J Minim Invasive Gynecol 16(5):540–550\nKyama CM et al (2009) Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis. Front Biosci (Elite Ed) 1(2):444–454\nScholl B et al (2009) Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis. Gynecol Endocrinol 25(11):701–706\nWei Y et al (2020) Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation 17(1):80\nMalvezzi H et al (2019) Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis. Reproduction 158(1):1–12\nSymons LK et al (2018) The immunopathophysiology of endometriosis. Trends Mol Med 24(9):748–762\nGarlanda C, Dinarello CA, Mantovani A (2013) The interleukin-1 family: back to the future. Immunity 39(6):1003–1018\nMichaud N et al (2011) Decreased concentrations of soluble interleukin-1 receptor accessory protein levels in the peritoneal fluid of women with endometriosis. J Reprod Immunol 92(1–2):68–73\nPeng B et al (2020) Role of interleukin-1beta in nerve growth factor expression, neurogenesis and deep dyspareunia in endometriosis. Hum Reprod 35(4):901–912\nYu J et al (2018) IL-1Beta stimulates brain-derived neurotrophic factor production in eutopic endometriosis stromal cell cultures: a model for cytokine regulation of neuroangiogenesis. Am J Pathol 188(10):2281–2292\nOkamura H et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378(6552):88–91\nArici A et al (2003) Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis. Fertil Steril 80(4):889–894\nOku H et al (2004) Role of IL-18 in pathogenesis of endometriosis. Hum Reprod 19(3):709–714\nMarvie P et al (2010) Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med 14(6B):1726–1739\nSantulli P et al (2012) Serum and peritoneal interleukin-33 levels are elevated in deeply infiltrating endometriosis. Hum Reprod 27(7):2001–2009\nDe Andrade VT et al (2017) Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis. Exp Ther Med 14(3):2317–2322\nVelasco I et al (2010) Interleukin-6 and other soluble factors in peritoneal fluid and endometriomas and their relation to pain and aromatase expression. J Reprod Immunol 84(2):199–205\nBourlev V et al (2018) Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain. Am J Reprod Immunol 80(3):e12857\nRapkin A et al (2000) Peritoneal fluid interleukin-6 in women with chronic pelvic pain. Fertil Steril 74(2):325–328\nGan XL et al (2010) Association of an interleukin-16 gene polymorphism with the risk and pain phenotype of endometriosis. DNA Cell Biol 29(11):663–667\nDrosdzol-Cop A, Skrzypulec-Plinta V, Stojko R (2012) Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain. Obstet Gynecol Surv 67(6):374–381\nBedaiwy MA et al (2002) Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 17(2):426–431\nAksak T et al (2021) Expression of monocyte chemotactic protein 2 and tumor necrosis factor alpha in human normal endometrium and endometriotic tissues. J Gynecol Obstet Hum Reprod 50(5):101971\nCho SH et al (2007) Evaluation of serum and urinary angiogenic factors in patients with endometriosis. Am J Reprod Immunol 58(6):497–504\nOthman ER et al (2016) Soluble tumor necrosis factor-alpha receptors in the serum of endometriosis patients. Eur J Obstet Gynecol Reprod Biol 200:1–5\nBullimore DW (2003) Endometriosis is sustained by tumour necrosis factor-alpha. Med Hypotheses 60(1):84–88\nOverton C et al (1996) Peritoneal fluid cytokines and the relationship with endometriosis and pain. Hum Reprod 11(2):380–386\nBinda MM, Donnez J, Dolmans MM (2017) Targeting mast cells: a new way to treat endometriosis. Expert Opin Ther Targets 21(1):67–75\nAnaf V et al (2006) Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis. Fertil Steril 86(5):1336–1343\nZhu TH et al (2018) Estrogen is an important mediator of mast cell activation in ovarian endometriomas. Reproduction 155(1):73–83\nKhan KN et al (2013) Pelvic pain in women with ovarian endometrioma is mostly associated with coexisting peritoneal lesions. Hum Reprod 28(1):109–118\nMcAllister SL et al (2016) Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents. Mol Cell Endocrinol 437:120–129\nWang H et al (2016) 1195 A/G promoter variants of the cyclooxygenase-2 gene increases the risk of pain occurrence in endometriotic women. Clin Exp Obstet Gynecol 43(2):254–257\nGreaves E et al (2017) EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Sci Rep 7:44169\nRuiz A et al (2018) Pharmacological blockage of the CXCR4-CXCL12 axis in endometriosis leads to contrasting effects in proliferation, migration, and invasion. Biol Reprod 98(1):4–14\nPluchino N et al (2018) G-protein-coupled receptor CXCR7 is overexpressed in human and murine endometriosis. Reprod Sci 25(8):1168–1174\nAksak T et al (2021) Expression of monocyte chemotactic protein 2 and tumor necrosis factor alpha in human normal endometrium and endometriotic tissues. J Gynecol Obstet Hum Reprod 50(5):10197\nMargari KM et al (2013) Peritoneal fluid concentrations of beta-chemokines in endometriosis. Eur J Obstet Gynecol Reprod Biol 169(1):103–107\nHornung D et al (2001) Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid. Mol Hum Reprod 7(2):163–168\nGardella B et al (2022) Endometriosis pain and epithelial neutrophil activating peptide-78 levels. Sci Rep 12(1):3227\nYang Y et al (2013) Elevated immunoreactivity of RANTES and CCR1 correlate with the severity of stages and dysmenorrhea in women with deep infiltrating endometriosis. Acta Histochem 115(5):434–439\nLiu Z et al (2018) Fractalkine/CX3CR1 contributes to endometriosis-induced neuropathic pain and mechanical hypersensitivity in rats. Front Cell Neurosci 12:495\nMalhotra N et al (2012) Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol Endocrinol 28(3):224–227\nManero MG, Alcazar JL (2010) Interleukin-8 serum levels do not correlate with pelvic pain in patients with ovarian endometriomas. Fertil Steril 94(2):450–452\nVitale SG et al (2018) The role of oxidative stress and membrane transport systems during endometriosis: a fresh look at a busy corner. Oxid Med Cell Longev 2018:7924021\nRocha MG et al (2015) Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis. Braz J Med Biol Res 48(4):363–369\nLaux-Biehlmann A, d’Hooghe T, Zollner TM (2015) Menstruation pulls the trigger for inflammation and pain in endometriosis. Trends Pharmacol Sci 36(5):270–276\nAsante A, Taylor RN (2011) Endometriosis: the role of neuroangiogenesis. Annu Rev Physiol 73:163–182\nTokushige N et al (2006) Nerve fibres in peritoneal endometriosis. Hum Reprod 21(11):3001–3007\nBerkley KJ et al (2004) Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci U S A 101(30):11094–11098\nTokushige N et al (2006) High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Hum Reprod 21(3):782–787\nTokushige N et al (2007) Different types of small nerve fibers in eutopic endometrium and myometrium in women with endometriosis. Fertil Steril 88(4):795–803\nAnaf V et al (2000) Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum Reprod 15(8):1744–1750\nAnaf V et al (2002) Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod 17(7):1895–1900\nZhang X et al (2010) Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis. Hum Reprod 25(2):392–397\nArnold J et al (2012) Imbalance between sympathetic and sensory innervation in peritoneal endometriosis. Brain Behav Immun 26(1):132–141\nArnold J et al (2013) Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal endometriosis. NeuroImmunoModulation 20(1):9–18\nTamburro S et al (2003) Expression of transforming growth factor β1 in nerve fibers is related to dysmenorrhea and laparoscopic appearance of endometriotic implants. Fertil Steril 80(5):1131–1136\nMechsner S et al (2007) Growth-associated protein 43-positive sensory nerve fibers accompanied by immature vessels are located in or near peritoneal endometriotic lesions. Fertil Steril 88(3):581–587\nKobayashi H et al (2014) Mechanism of pain generation for endometriosis-associated pelvic pain. Arch Gynecol Obstet 289(1):13–21\nKelleher JH, Tewari D, McMahon SB (2017) Neurotrophic factors and their inhibitors in chronic pain treatment. Neurobiol Dis 97(Pt B):127–138\nPeng B et al (2018) Nerve growth factor is associated with sexual pain in women with endometriosis. Reprod Sci 25(4):540–549\nWang G et al (2009) Rich innervation of deep infiltrating endometriosis. Hum Reprod 24(4):827–834\nRadzinsky V et al (2020) Pathogenesis of pelvic pain syndrome associated with endometriosis in patients resistant to surgical treatment. Gynecol Endocrinol 36(sup1):12–15\nJones AV et al (2016) Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus. Pain 157(11):2571–2581\nBarcena de Arellano ML et al (2013) Evidence of neurotrophic events due to peritoneal endometriotic lesions. Cytokine 62(2):253–61\nBarcena de Arellano ML et al (2011) Influence of nerve growth factor in endometriosis-associated symptoms. Reprod Sci 18(12):1202–10\nKajitani T et al (2013) Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis. Endocr J 60(10):1155–1164\nKasheh Farahani Z et al (2020) Assessing pain behavioral responses and neurotrophic factors in the dorsal root ganglion, serum and peritoneal fluid in rat models of endometriosis. J Family Reprod Health 14(4):259–268\nCappoli N et al (2020) The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception. J Neuroimmunol 349:577406\nWang S et al (2022) BDNF and TrKB expression levels in patients with endometriosis and their associations with dysmenorrhoea. J Ovarian Res 15(1):35\nDing S et al (2018) Role of brain-derived neurotrophic factor in endometriosis pain. Reprod Sci 25(7):1045–1057\nFilho P et al (2019) Peritoneal endometriosis induces time-related depressive- and anxiety-like alterations in female rats: involvement of hippocampal pro-oxidative and BDNF alterations. Metab Brain Dis 34(3):909–925\nPerricos A et al (2018) Increased serum levels of mBDNF in women with minimal and mild endometriosis have no predictive power for the disease. Exp Biol Med (Maywood) 243(1):50–56\nRocha AL et al (2017) Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis? Biomark Med 11(4):313–317\nWessels JM et al (2016) Assessing brain-derived neurotrophic factor as a novel clinical marker of endometriosis. Fertil Steril 105(1):119–28 e1–5\nBrowne AS et al (2012) Proteomic identification of neurotrophins in the eutopic endometrium of women with endometriosis. Fertil Steril 98(3):713–719\nIyengar S, Ossipov MH, Johnson KW (2017) The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain 158(4):543–559\nGrundy L, Erickson A, Brierley SM (2019) Visceral Pain. Annu Rev Physiol 81:261–284\nBerkley KJ, Rapkin AJ, Papka RE (2005) The pains of endometriosis. Science 308(5728):1587–1589\nMcMahon SB, Cafferty WB, Marchand F (2005) Immune and glial cell factors as pain mediators and modulators. Exp Neurol 192(2):444–462\nMorotti M et al (2014) Peripheral changes in endometriosis-associated pain. Hum Reprod Update 20(5):717–736\nBamps D et al (2021) TRP channel cooperation for nociception: therapeutic opportunities. Annu Rev Pharmacol Toxicol 61:655–677\nWang Y (2008) The functional regulation of TRPV1 and its role in pain sensitization. Neurochem Res 33(10):2008–2012\nPoli-Neto OB et al (2009) Increased capsaicin receptor TRPV1 in the peritoneum of women with chronic pelvic pain. Clin J Pain 25(3):218–222\nLiu J et al (2012) The expression and functionality of transient receptor potential vanilloid 1 in ovarian endometriomas. Reprod Sci 19(10):1110–1124\nRocha MG et al (2011) TRPV1 expression on peritoneal endometriosis foci is associated with chronic pelvic pain. Reprod Sci 18(6):511–515\nBohonyi N et al (2017) Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis. Mol Pain 13:1744806917705564\nNewman TA et al (2013) Expression of neuronal markers in the endometrium of women with and those without endometriosis. Hum Reprod 28(9):2502–2510\nSanchez AM et al (2016) Elevated systemic levels of endocannabinoids and related mediators across the menstrual cycle in women with endometriosis. Reprod Sci 23(8):1071–1079\nGreaves E et al (2014) Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis. J Clin Endocrinol Metab 99(9):E1738–E1743\nLian YL et al (2017) Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis. Mol Med Rep 16(2):1920–1926\nChaban VV (2008) Visceral sensory neurons that innervate both uterus and colon express nociceptive TRPv1 and P2X3 receptors in rats. Ethn Dis 18(2 Suppl 2):S2-20-4\nCastro J et al (2021) Pharmacological modulation of voltage-gated sodium (NaV) channels alters nociception arising from the female reproductive tract. Pain 162(1):227–242\nJoseph EK et al (2013) Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors. J Neurosci 33(7):2849–2859\nChiu IM, von Hehn CA, Woolf CJ (2012) Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat Neurosci 15(8):1063–1067\nJin X, Gereau RW (2006) Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci 26(1):246–55\nJung H et al (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104(1):254–263\nChen X et al (2011) TNF-alpha enhances the currents of voltage gated sodium channels in uninjured dorsal root ganglion neurons following motor nerve injury. Exp Neurol 227(2):279–286\nKao DJ et al (2012) CC chemokine ligand 2 upregulates the current density and expression of TRPV1 channels and Nav1.8 sodium channels in dorsal root ganglion neurons. J Neuroinflammation 9:189\nVelho RV et al (2021) Neurogenic inflammation in the context of endometriosis-what do we know? Int J Mol Sci 22(23)\nBrierley SM, Linden DR (2014) Neuroplasticity and dysfunction after gastrointestinal inflammation. Nat Rev Gastroenterol Hepatol 11(10):611–627\nMaddern J et al (2020) Pain in endometriosis. Front Cell Neurosci 14:590823\nHarrington AM et al (2012) Sprouting of colonic afferent central terminals and increased spinal mitogen-activated protein kinase expression in a mouse model of chronic visceral hypersensitivity. J Comp Neurol 520(10):2241–2255\nWoolf CJ (2011) Central sensitization: implications for the diagnosis and treatment of pain. Pain 152(3 Suppl):S2–S15\nNijs J et al (2011) How to explain central sensitization to patients with ‘unexplained’ chronic musculoskeletal pain: practice guidelines. Man Ther 16(5):413–418\nLaursen BS et al (2005) Health related quality of life and quantitative pain measurement in females with chronic non-malignant pain. Eur J Pain 9(3):267–275\nGrundstrom H et al (2019) Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis. Acta Obstet Gynecol Scand 98(3):327–336\nHe W et al (2010) Generalized hyperalgesia in women with endometriosis and its resolution following a successful surgery. Reprod Sci 17(12):1099–1111\nBajaj P et al (2003) Endometriosis is associated with central sensitization: a psychophysical controlled study. J Pain 4(7):372–380\nGerwin RD, Dommerholt J, Shah JP (2004) An expansion of Simons’ integrated hypothesis of trigger point formation. Curr Pain Headache Rep 8(6):468–475\nJarrell J (2011) Endometriosis and abdominal myofascial pain in adults and adolescents. Curr Pain Headache Rep 15(5):368–376\nRoss V, Detterman C, Hallisey A (2021) Myofascial pelvic pain: an overlooked and treatable cause of chronic pelvic pain. J Midwifery Womens Health 66(2):148–160\nAredo JV et al (2017) Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction. Semin Reprod Med 35(1):88–97\nStratton P et al (2015) Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain. Obstet Gynecol 125(3):719–728\nLara-Ramos A et al (2021) Widespread pain hypersensitivity and lumbopelvic impairments in women diagnosed with endometriosis. Pain Med 22(9):1970–1981\nPhan VT et al (2021) Widespread myofascial dysfunction and sensitisation in women with endometriosis-associated chronic pelvic pain: a cross-sectional study. Eur J Pain 25(4):831–840\nLarrosa Pardo F et al (2019) A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain. Eur J Pain 23(8):1563–1573\nBrawn J et al (2014) Central changes associated with chronic pelvic pain and endometriosis. Hum Reprod Update 20(5):737–747\nMay A (2011) Structural brain imaging: a window into chronic pain. Neuroscientist 17(2):209–220\nTu CH et al (2010) Brain morphological changes associated with cyclic menstrual pain. Pain 150(3):462–468\nTu CH et al (2013) Menstrual pain is associated with rapid structural alterations in the brain. Pain 154(9):1718–1724\nTu CH et al (2009) Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea. Neuroimage 47(1):28–35\nAs-Sanie S et al (2012) Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain 153(5):1006–1014\nAs-Sanie S et al (2016) Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. J Pain 17(1):1–13\nZheng P et al (2019) Evaluation of the brain functional activities in rats various location-endometriosis pain model. Ann Transl Med 7(23):767\nYano M et al (2019) Pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis. Hum Reprod 34(3):469–478\nZheng P et al (2020) Central sensitization-related changes in brain function activity in a rat endometriosis-associated pain model. J Pain Res 13:95–107\nLi T et al (2018) Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biol Reprod 99(2):349–359\nVincent K et al (2011) Dysmenorrhoea is associated with central changes in otherwise healthy women. Pain 152(9):1966–1975\nFilaretov AA, Bogdanov AI, Yarushkina NI (1996) Stress-induced analgesia. The role of hormones produced by the hypophyseal-adrenocortical system. Neurosci Behav Physiol 26(6):572–8\nQuinones M et al (2015) Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis. J Reprod Biol Health\nPetrelluzzi KF et al (2008) Salivary cortisol concentrations, stress and quality of life in women with endometriosis and chronic pelvic pain. Stress 11(5):390–397\nDodds KN et al (2019) Spinal glial adaptations occur in a minimally invasive mouse model of endometriosis: potential implications for lesion etiology and persistent pelvic pain. Reprod Sci 26(3):357–369\nOrr NL et al (2022) Central sensitization inventory in endometriosis. Pain 163(2):e234–e245\nMalykhina AP (2007) Neural mechanisms of pelvic organ cross-sensitization. Neuroscience 149(3):660–672\nChung MK et al (2002) The evil twins of chronic pelvic pain syndrome: endometriosis and interstitial cystitis. JSLS 6(4):311–314\nMorrison TC et al (2006) Opposing viscerovisceral effects of surgically induced endometriosis and a control abdominal surgery on the rat bladder. Fertil Steril 86(4 Suppl):1067–1073\nGiamberardino MA et al (2002) Influence of endometriosis on pain behaviors and muscle hyperalgesia induced by a ureteral calculosis in female rats. Pain 95(3):247–257\nGiamberardino MA et al (2001) Modulation of pain and hyperalgesia from the urinary tract by algogenic conditions of the reproductive organs in women. Neurosci Lett 304(1–2):61–64\nBerkley KJ et al (2007) Endometriosis-induced vaginal hyperalgesia in the rat: effect of estropause, ovariectomy, and estradiol replacement. Pain 132(Suppl 1):S150–S159\nCason AM, Samuelsen CL, Berkley KJ (2003) Estrous changes in vaginal nociception in a rat model of endometriosis. Horm Behav 44(2):123–131\nTaylor DC, Pierau FK, Schmid H (1983) The use of fluorescent tracers in the peripheral sensory nervous system. J Neurosci Methods 8(3):211–224\nDawson NJ, Schmid H, Pierau FK (1992) Pre-spinal convergence between thoracic and visceral nerves of the rat. Neurosci Lett 138(1):149–152\nGe P et al (2019) Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk. Pain 160(11):2566–2579\nWang Y et al (2015) Upregulation of alpha(2)delta-1 calcium channel subunit in the spinal cord contributes to pelvic organ cross-sensitization in a rat model of experimentally-induced endometriosis. Neurochem Res 40(6):1267–1273\nChen Z et al (2015) Activation of p38 MAPK in the rostral ventromedial medulla by visceral noxious inputs transmitted via the dorsal columns may contribute to pelvic organ cross-sensitization in rats with endometriosis. Neuroscience 291:272–278\nStratton P, Berkley KJ (2011) Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update 17(3):327–346\nPractice Committee of the American Society for Reproductive (2014) Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril 101(4):927–35\nChapron C et al (2019) Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 15(11):666–682\nPractice Bulletin No. 114 (2010) Management of endometriosis. Obstet Gynecol 116(1):223–236\nMarjoribanks J et al (2015) Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev 7:CD001751\nKauppila A, Puolakka J, Ylikorkala O (1979) Prostaglandin biosynthesis inhibitors and endometriosis. Prostaglandins 18(4):655–661\nKauppila A, Ronnberg L (1985) Naproxen sodium in dysmenorrhea secondary to endometriosis. Obstet Gynecol 65(3):379–383\nCobellis L et al (2004) The treatment with a COX-2 specific inhibitor is effective in the management of pain related to endometriosis. Eur J Obstet Gynecol Reprod Biol 116(1):100–102\nDmitrieva N et al (2012) Telemetric assessment of referred vaginal hyperalgesia and the effect of indomethacin in a rat model of endometriosis. Front Pharmacol 3:158\nBrown J et al (2017) Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev 1:CD004753\nKalaitzopoulos DR et al (2021) Treatment of endometriosis: a review with comparison of 8 guidelines. BMC Womens Health 21(1):397\nMeresman GF et al (2002) Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic endometrial tissue from patients with endometriosis. Fertil Steril 77(6):1141–1147\nTokushige N et al (2009) Effect of progestogens and combined oral contraceptives on nerve fibers in peritoneal endometriosis. Fertil Steril 92(4):1234–1239\nBrown J et al (2018) Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev 5:CD001019\nVercellini P et al (1993) A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis. Fertil Steril 60(1):75–79\nZhao Y, Luan X, Wang Y (2021) Letrozole combined with oral contraceptives versus oral contraceptives alone in the treatment of endometriosis-related pain symptoms: a pilot study. Gynecol Endocrinol 37(1):51–55\nVercellini P et al (2002) Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis. Fertil Steril 77(1):52–61\nFedele L et al (1989) Comparison of cyproterone acetate and danazol in the treatment of pelvic pain associated with endometriosis. Obstet Gynecol 73(6):1000–1004\nGuzick DS et al (2011) Randomized trial of leuprolide versus continuous oral contraceptives in the treatment of endometriosis-associated pelvic pain. Fertil Steril 95(5):1568–1573\nEl Taha L et al (2021) Efficacy of dienogest vs combined oral contraceptive on pain associated with endometriosis: randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 267:205–212\nAlcalde AM et al (2022) Assessment of quality of life, sexual quality of life, and pain symptoms in deep infiltrating endometriosis patients with or without associated adenomyosis and the influence of a flexible extended combined oral contraceptive regimen: results of a prospective, observational study. J Sex Med 19(2):311–318\nPiacenti I et al (2021) Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what’s the best choice? Gynecol Endocrinol 37(5):471–475\nHarada T et al (2008) Low-dose oral contraceptive pill for dysmenorrhea associated with endometriosis: a placebo-controlled, double-blind, randomized trial. Fertil Steril 90(5):1583–1588\nHarada T et al (2017) Ethinylestradiol 20 mug/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial. Fertil Steril 108(5):798–805\nRazzi S et al (2007) Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. Eur J Obstet Gynecol Reprod Biol 135(2):188–190\nCaruso S et al (2011) Conventional vs. extended-cycle oral contraceptives on the quality of sexual life: comparison between two regimens containing 3 mg drospirenone and 20 microg ethinyl estradiol. J Sex Med 8(5):1478–85\nTanaka Y et al (2016) Effects of low-dose combined drospirenone-ethinylestradiol on perimenstrual symptoms experienced by women with endometriosis. Int J Gynaecol Obstet 135(2):135–139\nTaniguchi F et al (2015) Effects of low dose oral contraceptive pill containing drospirenone/ethinylestradiol in patients with endometrioma. Eur J Obstet Gynecol Reprod Biol 191:116–120\nCaruso S et al (2016) Comparative, open-label prospective study on the quality of life and sexual function of women affected by endometriosis-associated pelvic pain on 2 mg dienogest/30 microg ethinyl estradiol continuous or 21/7 regimen oral contraceptive. J Endocrinol Invest 39(8):923–931\nOlive DL (2003) Medical therapy of endometriosis. Semin Reprod Med 21(2):209–222\nLaschke MW, Menger MD (2012) Anti-angiogenic treatment strategies for the therapy of endometriosis. Hum Reprod Update 18(6):682–702\nBergqvist A, Theorell T (2001) Changes in quality of life after hormonal treatment of endometriosis. Acta Obstet Gynecol Scand 80(7):628–637\nSchlaff WD et al (2006) Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril 85(2):314–325\nVercellini P et al (1996) Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis. Am J Obstet Gynecol 175(2):396–401\nHarada T et al (2009) Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis—a randomized, double-blind, multicenter, controlled trial. Fertil Steril 91(3):675–681\nStrowitzki T et al (2010) Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod 25(3):633–641\nCosson M et al (2002) Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study. Fertil Steril 77(4):684–692\nUludag SZ et al (2021) Dienogest reduces endometrioma volume and endometriosis-related pain symptoms. J Obstet Gynaecol 41(8):1246–1251\nBromham DR et al (1995) Updating the clinical experience in endometriosis—the European perspective. Br J Obstet Gynaecol 102(Suppl 12):12–16\nFedele L et al (1989) Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril 51(5):781–785\nGestrinone Italian Study Group (1996) Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Fertil Steril 66(6):911–9\nOverton CE et al (1994) A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis. Fertil Steril 62(4):701–707\nTelimaa S et al (1987) Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol 1(1):13–23\nSukhikh GT et al (2021) Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. Fertil Steril 116(6):1568–1577\nCarvalho N et al (2018) Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial. Fertil Steril 110(6):1129–1136\nBrown J, Kives S, Akhtar M (2012) Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database Syst Rev 3:CD002122\nBuggio L et al (2017) Oral and depot progestin therapy for endometriosis: towards a personalized medicine. Expert Opin Pharmacother 18(15):1569–1581\nBrown J, Pan A, Hart RJ (2010) Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev 12:CD008475\nFranssen AM et al (1989) Endometriosis: treatment with gonadotropin-releasing hormone agonist Buserelin. Fertil Steril 51(3):401–408\nAlmassinokiani F et al (2013) Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis. Med Sci Monit 19:534–539\nMorelli M et al (2013) Improvement in chronic pelvic pain after gonadotropin releasing hormone analogue (GnRH-a) administration in premenopausal women suffering from adenomyosis or endometriosis: a retrospective study. Gynecol Endocrinol 29(4):305–308\nLi Z et al (2014) A randomized study comparing the side effects and hormonal status of triptorelin and leuprorelin following conservative laparoscopic surgery for ovarian endometriosis in Chinese women. Eur J Obstet Gynecol Reprod Biol 183:164–168\nSadler Gallagher J et al (2017) The effects of gonadotropin-releasing hormone agonist combined with add-back therapy on quality of life for adolescents with endometriosis: a randomized controlled trial. J Pediatr Adolesc Gynecol 30(2):215–222\nAgarwal SK et al (2015) Treatment of endometriosis with the GnRHa deslorelin and add-back estradiol and supplementary testosterone. Biomed Res Int 2015:934164\nZhu SY et al (2021) Preventive therapeutic options for postoperative recurrence of ovarian endometrioma: gonadotropin-releasing hormone agonist with or without levonorgestrel intrauterine system insertion. Arch Gynecol Obstet 303(2):533–539\nGallagher JS et al (2018) Long-term effects of gonadotropin-releasing hormone agonists and add-back in adolescent endometriosis. J Pediatr Adolesc Gynecol 31(4):376–381\nHowell R et al (1995) Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Fertil Steril 64(3):474–481\nKitawaki J et al (2011) Maintenance therapy with dienogest following gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Eur J Obstet Gynecol Reprod Biol 157(2):212–216\nKitawaki J et al (2008) Maintenance therapy involving a tapering dose of danazol or mid/low doses of oral contraceptive after gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Fertil Steril 89(6):1831–1835\nLamvu G et al (2019) Patterns of prescription opioid use in women with endometriosis: evaluating prolonged use, daily dose, and concomitant use with benzodiazepines. Obstet Gynecol 133(6):1120–1130\nSinclair J et al (2021) Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. PLoS ONE 16(10):e0258940\nChiuve SE et al (2021) Chronic opioid use and complication risks in women with endometriosis: a cohort study in US administrative claims. Pharmacoepidemiol Drug Saf 30(6):787–796\nTaylor HS et al (2017) Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 377(1):28–40\nSelak V et al (2007) Danazol for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 2007(4):CD000068\nSoysal S et al (2004) The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 19(1):160–167\nPavone ME, Bulun SE (2012) Aromatase inhibitors for the treatment of endometriosis. Fertil Steril 98(6):1370–1379\nVercellini P et al (1993) A gonadotropin-releasing hormone agonist versus a low-dose oral contraceptive for pelvic pain associated with endometriosis**This work was conducted within the framework of the Italian National Research Council Applied Project “Prevention and Control of Disease Factors,” subproject 5 (Fertility Control), grant no. 91.00131.PF41.115.05532, Milan, Italy.††Presented at the 48th Annual Meeting of the American Fertility Society, New Orleans, Louisiana, November 2 to 5, 1992. Fertil Steril 60(1):75–79\nRezende GP et al (2022) Surgery vs. hormone-based treatment for pain control in deep infiltrating endometriosis: a retrospective cohort study. Curr Med Res Opin 38(4):641–647\nChapron C et al (2002) Management of ovarian endometriomas. Hum Reprod Update 8(6):591–597\nRindos NB, Fulcher IR, Donnellan NM (2020) Pain and quality of life after laparoscopic excision of endometriosis. J Minim Invasive Gynecol 27(7):1610–1617\nSutton CJ et al (1994) Prospective, randomized, double-blind, controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal, mild, and moderate endometriosis. Fertil Steril 62(4):696–700\nBastu E et al (2020) Improvement in quality of life and pain scores after laparoscopic management of deep endometriosis: a retrospective cohort study. Arch Gynecol Obstet 302(1):165–172\nParra RS et al (2021) The impact of laparoscopic surgery on the symptoms and wellbeing of patients with deep infiltrating endometriosis and bowel involvement. J Psychosom Obstet Gynaecol 42(1):75–80\nMisal M, Girardo M, Wasson MN (2021) Surgical decision regret in women pursuing surgery for endometriosis or chronic pelvic pain. J Minim Invasive Gynecol 28(7):1343–1350\nBafort C et al (2020) Laparoscopic surgery for endometriosis. Cochrane Database Syst Rev 10:CD011031\nHealey M, Ang WC, Cheng C (2010) Surgical treatment of endometriosis: a prospective randomized double-blinded trial comparing excision and ablation. Fertil Steril 94(7):2536–2540\nJacobson TZ et al (2009) Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 2009(4):CD001300\nCore G et al (2022) Members of the endometriosis guideline, ESHRE guideline: endometriosis. Hum Reprod Open 2022(2):hoac009\nMisra G et al (2020) Laparoscopic ablation or excision with helium thermal coagulator versus electrodiathermy for the treatment of mild-to-moderate endometriosis: randomised controlled trial. BJOG 127(12):1528–1535\nRaffi F, Metwally M, Amer S (2012) The impact of excision of ovarian endometrioma on ovarian reserve: a systematic review and meta-analysis. J Clin Endocrinol Metab 97(9):3146–3154\nSandstrom A et al (2020) Effect of hysterectomy on pain in women with endometriosis: a population-based registry study. BJOG 127(13):1628–1635\nIanieri MM et al (2022) Impact of nerve-sparing posterolateral parametrial excision for deep infiltrating endometriosis on postoperative bowel, urinary, and sexual function. Int J Gynaecol Obstet\nAngioni S et al (2015) Pain control and quality of life after laparoscopic en-block resection of deep infiltrating endometriosis (DIE) vs. incomplete surgical treatment with or without GnRHa administration after surgery. Arch Gynecol Obstet 291(2):363–70\nCheong Y et al (2008) Laparoscopic surgery for endometriosis: how often do we need to re-operate? J Obstet Gynaecol 28(1):82–85\nVercellini P et al (2003) Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial. Fertil Steril 80(2):310–319\nCandiani GB et al (1992) Presacral neurectomy for the treatment of pelvic pain associated with endometriosis: a controlled study. Am J Obstet Gynecol 167(1):100–103\nZullo F et al (2003) Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial. Am J Obstet Gynecol 189(1):5–10\nProctor ML et al (2005) Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 4:CD001896\nMiller LE, Bhattacharyya R, Miller VM (2020) Clinical utility of presacral neurectomy as an adjunct to conservative endometriosis surgery: systematic review and meta-analysis of controlled studies. Sci Rep 10(1):6901\nAgnello M, Vottero M, Bertapelle P (2021) Sacral neuromodulation to treat voiding dysfunction in patients with previous pelvic surgery for deep infiltrating endometriosis: our centre’s experience. Int Urogynecol J 32(6):1499–1504\nKanellos P et al (2021) Postoperative pain is driven by preoperative pain, not by endometriosis. J Clin Med 10(20)\nChen I et al (2020) Pre- and postsurgical medical therapy for endometriosis surgery. Cochrane Database Syst Rev 11:CD003678\nCapezzuoli T et al (2021) Long-term hormonal treatment reduces repetitive surgery for endometriosis recurrence. Reprod Biomed Online 42(2):451–456\nLoverro G et al (2008) A randomized study comparing triptorelin or expectant management following conservative laparoscopic surgery for symptomatic stage III-IV endometriosis. Eur J Obstet Gynecol Reprod Biol 136(2):194–198\nVercellini P et al (2003) Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril 80(3):560–563\nGranese R et al (2015) Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial. Acta Obstet Gynecol Scand 94(6):637–645\nCheewadhanaraks S et al (2012) Postoperative depot medroxyprogesterone acetate versus continuous oral contraceptive pills in the treatment of endometriosis-associated pain: a randomized comparative trial. Gynecol Obstet Invest 74(2):151–156\nMehdizadeh Kashi A et al (2022) A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis. Int J Gynaecol Obstet 156(1):124–132\nTanmahasamut P et al (2017) Postoperative desogestrel for pelvic endometriosis-related pain: a randomized controlled trial. Gynecol Endocrinol 33(7):534–539\nHornstein MD et al (1997) Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 68(5):860–864\nMuzii L et al (2016) Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis. Am J Obstet Gynecol 214(2):203–211\nSeracchioli R et al (2010) Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial. Fertil Steril 94(2):464–471\nTriantafyllidou O et al (2022) Time to full effect, following treatment with combined oral contraceptives (cyclic versus continuous administration) in patients with endometriosis after laparoscopic surgery: a prospective cohort study. Hum Fertil (Camb) 25(1):72–79\nLong QQ et al (2010) Clinical efficacy and safety of gonadotropin releasing hormone agonist combined with estrogen-dydrogesteronea in treatment of endometriosis. Zhonghua Fu Chan Ke Za Zhi 45(4):247–251\nSesti F et al (2007) Hormonal suppression treatment or dietary therapy versus placebo in the control of painful symptoms after conservative surgery for endometriosis stage III–IV. A randomized comparative trial. Fertil Steril 88(6):1541–1547\nPattanittum P et al (2016) Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev 3:CD002124\nKrabbenborg I et al (2021) Diet quality and perceived effects of dietary changes in Dutch endometriosis patients: an observational study. Reprod Biomed Online 43(5):952–961\nChandrareddy A et al (2008) Adverse effects of phytoestrogens on reproductive health: a report of three cases. Complement Ther Clin Pract 14(2):132–135\nHuijs E, Nap A (2020) The effects of nutrients on symptoms in women with endometriosis: a systematic review. Reprod Biomed Online 41(2):317–328\nAmini L et al (2021) The effect of combined vitamin C and vitamin E supplementation on oxidative stress markers in women with endometriosis: a randomized, triple-blind placebo-controlled clinical trial. Pain Res Manag 2021:5529741\nNodler JL et al (2020) Supplementation with vitamin D or omega-3 fatty acids in adolescent girls and young women with endometriosis (SAGE): a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 112(1):229–236\nAlmassinokiani F et al (2016) Effects of vitamin D on endometriosis-related pain: a double-blind clinical trial. Med Sci Monit 22:4960–4966\nPorpora MG et al (2013) A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine. Evid Based Complement Alternat Med 2013:240702\nMorales-Prieto DM et al (2018) Comparison of dienogest effects upon 3,3’-diindolylmethane supplementation in models of endometriosis and clinical cases. Reprod Biol 18(3):252–258\nDe Leo V et al (2019) Role of a natural integrator based on lipoic acid, palmitoiletanolamide and myrrh in the treatment of chronic pelvic pain and endometriosis. Minerva Ginecol 71(3):191–195\nZhu X, Hamilton KD, McNicol ED (2011) Acupuncture for pain in endometriosis. Cochrane Database Syst Rev 9:CD007864\nXu Y et al (2017) Effects of acupuncture for the treatment of endometriosis-related pain: a systematic review and meta-analysis. PLoS ONE 12(10):e0186616\nLund I, Lundeberg T (2016) Is acupuncture effective in the treatment of pain in endometriosis? J Pain Res 9:157–165\nRubi-Klein K et al (2010) Is acupuncture in addition to conventional medicine effective as pain treatment for endometriosis? A randomised controlled cross-over trial. Eur J Obstet Gynecol Reprod Biol 153(1):90–93\nArmour M et al (2021) Manual acupuncture plus usual care versus usual care alone in the treatment of endometriosis-related chronic pelvic pain: a randomized controlled feasibility study. J Altern Complement Med 27(10):841–849\nPayne JA (2019) Acupuncture for endometriosis: a case study. Med Acupunct 31(6):392–394\nHighfield ES et al (2006) Adolescent endometriosis-related pelvic pain treated with acupuncture: two case reports. J Altern Complement Med 12(3):317–322\nXiang DF, Sun QZ, Liang XF (2011) Effect of abdominal acupuncture on pain of pelvic cavity in patients with endometriosis. Zhongguo Zhen Jiu 31(2):113–116\nWayne PM et al (2008) Japanese-style acupuncture for endometriosis-related pelvic pain in adolescents and young women: results of a randomized sham-controlled trial. J Pediatr Adolesc Gynecol 21(5):247–257\nSharma N, Rekha K, Srinivasan JK (2017) Efficacy of transcutaneous electrical nerve stimulation in the treatment of chronic pelvic pain. J Midlife Health 8(1):36–39\nMira TAA et al (2020) Hormonal treatment isolated versus hormonal treatment associated with electrotherapy for pelvic pain control in deep endometriosis: randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 255:134–141\nZhang X, Li W (2015) Efficacy on endometriosis treated with electroacupuncture. Zhongguo Zhen Jiu 35(4):323–326\nJin YB, Sun ZL, Jin HF (2009) Randomized controlled study on ear-electroacupuncture treatment of endometriosis-induced dysmenorrhea in patients. Zhen Ci Yan Jiu 34(3):188–192\nAmirsalari S et al (2021) The effect of garlic tablets on the endometriosis-related pains: a randomized placebo-controlled clinical trial. Evid Based Complement Alternat Med 2021:5547058\nMeresman GF, Gotte M, Laschke MW (2021) Plants as source of new therapies for endometriosis: a review of preclinical and clinical studies. Hum Reprod Update 27(2):367–392\nMaia H Jr et al (2012) Advantages of the association of resveratrol with oral contraceptives for management of endometriosis-related pain. Int J Womens Health 4:543–549\nMendes da Silva D et al (2017) The use of resveratrol as an adjuvant treatment of pain in endometriosis: a randomized clinical trial. J Endocr Soc 1(4):359–369\nGiugliano E et al (2013) The adjuvant use of N-palmitoylethanolamine and transpolydatin in the treatment of endometriotic pain. Eur J Obstet Gynecol Reprod Biol 168(2):209–213\nCobellis L et al (2011) Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)-transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study. Eur J Obstet Gynecol Reprod Biol 158(1):82–86\nIndraccolo U, Barbieri F (2010) Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: preliminary observations. Eur J Obstet Gynecol Reprod Biol 150(1):76–79\nZheng Y, Liu X, Guo SW (2012) Therapeutic potential of andrographolide for treating endometriosis. Hum Reprod 27(5):1300–1313\nFlower A et al (2012) Chinese herbal medicine for endometriosis. Cochrane Database Syst Rev 5:CD006568\nZhao RH et al (2013) Chinese medicine improves postoperative quality of life in endometriosis patients: a randomized controlled trial. Chin J Integr Med 19(1):15–21\nTaniguchi F et al (2020) Efficacy of Tokishakuyakusan add-on therapy with low-dose oral contraceptive pills on endometriosis patients with dysmenorrhea. J Obstet Gynaecol Res 46(11):2280–2286\nLi Y, Li T, Song S (2017) Evaluation of efficacy and safety of Dan’e-Fukang soft extract in the treatment of endometriosis: a meta-analysis of 39 randomized controlled trials enrolling 5442 patients. Evid Based Complement Alternat Med 2017:9767391\nShan J et al (2017) Meta-analysis of Chinese traditional medicine Bushen Huoxue prescription for endometriosis treatment. Evid Based Complement Alternat Med 2017:5416423\nLin Y et al (2022) Efficacy and safety of Chinese herbal medicine for endometriosis associated pain. Am J Chin Med 50(4):1095–1111\nTennfjord MK, Gabrielsen R, Tellum T (2021) Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review. BMC Womens Health 21(1):355\nAwad E et al (2017) Efficacy of exercise on pelvic pain and posture associated with endometriosis: within subject design. J Phys Ther Sci 29(12):2112–2115\nGoncalves AV, Barros NF, Bahamondes L (2017) The practice of Hatha Yoga for the treatment of pain associated with endometriosis. J Altern Complement Med 23(1):45–52\nCarpenter SE et al (1995) The effect of regular exercise on women receiving danazol for treatment of endometriosis. Int J Gynaecol Obstet 49(3):299–304\nHernandez S et al (2015) Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord 7(3):89–114\nPoli-Neto OB et al (2020) Strength exercise has different effects on pressure pain thresholds in women with endometriosis-related symptoms and healthy controls: a quasi-experimental study. Pain Med 21(10):2280–2287\nValiani M et al (2010) The effects of massage therapy on dysmenorrhea caused by endometriosis. Iran J Nurs Midwifery Res 15(4):167–171\nLi T et al (2022) CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial. Zhongguo Zhen Jiu 42(4):397–401\nChen LF et al (2020) Herb-separated moxibustion on dysmenorrhea in ovarian endometriosis: a randomized controlled trial. Zhongguo Zhen Jiu 40(7):717–720\nSchwartz ASK et al (2019) The use of home remedies and complementary health approaches in endometriosis. Reprod Biomed Online 38(2):260–271\nYao Z et al (2005) Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds. J Invest Surg 18(4):177–183\nStratton P et al (2008) Return of chronic pelvic pain from endometriosis after raloxifene treatment: a randomized controlled trial. Obstet Gynecol 111(1):88–96\nFlores VA, Stachenfeld NS, Taylor HS (2018) Bazedoxifene-conjugated estrogens for treating endometriosis. Obstet Gynecol 132(2):475–477\nHarada T et al (2017) SR-16234, a novel selective estrogen receptor modulator for pain symptoms with endometriosis: an open-label clinical trial. Yonago Acta Med 60(4):227–233\nFu J et al (2017) Progesterone receptor modulators for endometriosis. Cochrane Database Syst Rev 7:CD009881\nChwalisz C, Mattia-Goldberg K et al (2004) Treatment of endometriosis with the novel selective progesterone receptor modulator (SPRM) asoprisnil. Fertil Steril 82:S83–S84\nBressler LH et al (2017) Treatment of endometriosis-related chronic pelvic pain with Ulipristal Acetate and associated endometrial changes. HSOA J Reprod Med Gynaecol Obstet\nSingh SS et al (2020) Ulipristal acetate prior to surgery for endometriosis. Reprod Sci 27(9):1707–1714\nChung MS, Han SJ (2022) Endometriosis-associated angiogenesis and anti-angiogenic therapy for endometriosis. Front Glob Womens Health 3:856316\nBouquet de Joliniere J et al (2021) Antiangiogenic therapy as a new strategy in the treatment of endometriosis? The first case report. Front Surg 8:791686\nNovella-Maestre E et al (2012) Effect of antiangiogenic treatment on peritoneal endometriosis-associated nerve fibers. Fertil Steril 98(5):1209–1217\nDiVasta AD et al (2021) Nonhormonal therapy for endometriosis: a randomized, placebo-controlled, pilot study of cabergoline versus norethindrone acetate. F S Rep 2(4):454–461\nKoninckx PR et al (2008) Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 23(9):2017–2023\nKaplan S, Kirici P, Turk A (2022) The effects of adalimumab on the rat autotransplantation endometriosis model: a placebo-controlled randomized study. Adv Clin Exp Med\nLu D, Song H, Shi G (2013) Anti-TNF-alpha treatment for pelvic pain associated with endometriosis. Cochrane Database Syst Rev 3:CD008088\nCulley L et al (2013) The social and psychological impact of endometriosis on women’s lives: a critical narrative review. Hum Reprod Update 19(6):625–639\nReis FM et al (2020) Is stress a cause or a consequence of endometriosis? Reprod Sci 27(1):39–45\nCavaggioni G et al (2014) Are mood and anxiety disorders and alexithymia associated with endometriosis? A preliminary study. Biomed Res Int 2014:786830\nVuontisjarvi S et al (2018) The long-term footprint of endometriosis: population-based cohort analysis reveals increased pain symptoms and decreased pain tolerance at age 46 years. J Pain 19(7):754–763\nEriksen HL et al (2008) Psychological aspects of endometriosis: differences between patients with or without pain on four psychological variables. Eur J Obstet Gynecol Reprod Biol 139(1):100–105\nFacchin F et al (2016) Personality in women with endometriosis: temperament and character dimensions and pelvic pain. Hum Reprod 31(7):1515–1521\nJones GT (2016) Psychosocial vulnerability and early life adversity as risk factors for central sensitivity syndromes. Curr Rheumatol Rev 12(2):140–153\nHernandez S et al (2017) Impact of psychological stress on pain perception in an animal model of endometriosis. Reprod Sci 24(10):1371–1381\nCasalechi M et al (2021) Endometriosis and related pelvic pain: association with stress, anxiety and depressive symptoms. Minerva Obstet Gynecol 73(3):283–289\nRoth RS, Punch M, Bachman JE (2011) Psychological factors in chronic pelvic pain due to endometriosis: a comparative study. Gynecol Obstet Invest 72(1):15–19\nPope CJ et al (2015) A systematic review of the association between psychiatric disturbances and endometriosis. J Obstet Gynaecol Can 37(11):1006–1015\nvan Barneveld E et al (2022) Depression, anxiety, and correlating factors in endometriosis: a systematic review and meta-analysis. J Womens Health (Larchmt) 31(2):219–230\nde Barros Meneguetti M et al (2023) Assessment of quality of life and psychological repercussions in women with endometriosis according to pain intensity. Psychol Health Med 28(3):660–669\nde Franca Moreira M, Gamboa OL, Pinho Oliveira MA (2021) Association between severity of pain, perceived stress and vagally-mediated heart rate variability in women with endometriosis. Women Health 61(10):937–946\nFacchin F et al (2021) Sleep disturbances, fatigue and psychological health in women with endometriosis: a matched pair case-control study. Reprod Biomed Online 43(6):1027–1034\nFacchin F et al (2017) Mental health in women with endometriosis: searching for predictors of psychological distress. Hum Reprod 32(9):1855–1861\nOlliges E et al (2021) The physical, psychological, and social day-to-day experience of women living with endometriosis compared to healthy age-matched controls—a mixed-methods study. Front Glob Womens Health 2:767114\nZarbo C et al (2019) Cognitive and personality factors implicated in pain experience in women with endometriosis: a mixed-method study. Clin J Pain 35(12):948–957\nMcPeak AE et al (2018) Pain catastrophizing and pain health-related quality-of-life in endometriosis. Clin J Pain 34(4):349–356\nMuharam R et al (2022) Chronic pelvic pain in women with endometriosis is associated with psychiatric disorder and quality of life deterioration. Int J Womens Health 14:131–138\nCulley L et al (2017) A qualitative study of the impact of endometriosis on male partners. Hum Reprod 32(8):1667–1673\nFourquet J et al (2010) Patients’ report on how endometriosis affects health, work, and daily life. Fertil Steril 93(7):2424–2428\nSullivan-Myers C et al (2021) Delineating sociodemographic, medical and quality of life factors associated with psychological distress in individuals with endometriosis. Hum Reprod 36(8):2170–2180\nVercellini P et al (2018) Medical treatment or surgery for colorectal endometriosis? Results of a shared decision-making approach. Hum Reprod 33(2):202–211\nVercellini P et al (2016) Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril 105(3):734–743\nVan den Broeck U et al (2013) Effect of laparoscopic surgery for moderate and severe endometriosis on depression, relationship satisfaction and sexual functioning: comparison of patients with and without bowel resection. Hum Reprod 28(9):2389–2397\nMardon AK et al (2021) Treatment recommendations for the management of persistent pelvic pain: a systematic review of international clinical practice guidelines. BJOG\nEvans S et al (2019) Psychological and mind-body interventions for endometriosis: a systematic review. J Psychosom Res 124:109756\nDonatti L et al (2022) Cognitive behavioral therapy in endometriosis, psychological based intervention: a systematic review. Rev Bras Ginecol Obstet 44(3):295–303\nSamami E et al (2023) Pain-focused psychological interventions in women with endometriosis: a systematic review. Neuropsychopharmacol Rep\nMoreira MF, Gamboa OL, Pinho Oliveira MA (2022) A single-blind, randomized, pilot study of a brief mindfulness-based intervention for the endometriosis-related pain management. Eur J Pain 26(5):1147–1162\nZhao L et al (2012) Effects of progressive muscular relaxation training on anxiety, depression and quality of life of endometriosis patients under gonadotrophin-releasing hormone agonist therapy. Eur J Obstet Gynecol Reprod Biol 162(2):211–215\nSchubert K et al (2022) Internet-based cognitive behavioral therapy for improving health-related quality of life in patients with endometriosis: study protocol for a randomized controlled trial. Trials 23(1):300\nDella Corte L et al (2020) The burden of endometriosis on women's lifespan: a narrative overview on quality of life and psychosocial wellbeing. Int J Environ Res Public Health 17(13)\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEditor information\nEditors and Affiliations\nRights and permissions\nCopyright information\n© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG\nAbout this chapter\nCite this chapter\nLin, Y., Wang, C.C. (2024). Neuroimmunology of Endometriosis-Associated Pain and Its Psychological Aspects. In: Rezaei, N., Yazdanpanah, N. (eds) PsychoNeuroImmunology. Integrated Science, vol 31. Springer, Cham. https://doi.org/10.1007/978-3-031-72079-6_30\nDownload citation\nDOI: https://doi.org/10.1007/978-3-031-72079-6_30\nPublished:\nPublisher Name: Springer, Cham\nPrint ISBN: 978-3-031-72078-9\nOnline ISBN: 978-3-031-72079-6\neBook Packages: MedicineMedicine (R0)","source_license":"CC0","license_restricted":false}