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Preclinical models of female pelvic pain disorders.

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Title: Preclinical models of female pelvic pain disorders.
Authors: Scuffi I; Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy., Marini M; Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy., Petraglia F; Department of Experimental, Clinical and Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy.; Department of Maternal and Child Health, Careggi University Hospital, Florence, Italy., Landini L; Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy., Nassini R; Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy., De Logu F; Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Florence, Florence, Italy.
Source: Pain [Pain] 2026 Aug 01; Vol. 167 (8), pp. 1767-1780. Date of Electronic Publication: 2026 May 20.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7508686 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6623 (Electronic) Linking ISSN: 03043959 NLM ISO Abbreviation: Pain Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Amsterdam, Elsevier/North-Holland.
MeSH Terms: Pelvic Pain*/physiopathology , Disease Models, Animal*, Female ; Animals ; Humans ; Vulvodynia
Abstract: Abstract: Pain is influenced by a complex interplay of biological, psychological, and social factors. Sex has emerged as a key determinant of vulnerability to chronic pain and a major risk factor for poor response to available pharmacological treatments. Women report higher rates of chronic pain and exhibit greater pain sensitivity; however, the underlying mechanisms remain poorly understood. Preclinical models are essential to uncover sex-specific biological pathways involved in pain and to guide the development of novel, targeted therapies through translational approaches. This review summarizes animal models of female-associated pelvic pain disorders, including endometriosis, adenomyosis, dysmenorrhea, vulvodynia, interstitial cystitis, uterine leiomyomas, chronic pelvic pain, and pelvic inflammatory disease. These models recapitulate key features such as lesion biology, neuroimmune interactions, and pain behaviors also observed in patients. However, current models still face limitations in capturing spontaneous pain dynamics, hormonal complexity, and psychosocial influences. Refining and integrating biological, behavioral, and sex-specific endpoints will be crucial to enhance their translational relevance and advance precision pain therapies for women.
(Copyright © 2026 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)
References: Gonadotropin Releasing Hormone (GnRH) Analogues. LiverTox: clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012.
ACOG Committee Opinion No. 760. Dysmenorrhea and endometriosis in the adolescent. Obstet Gynecol 2018;132:e249–e258.
Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R. Laparoscopic excision of endometriosis: a randomized, placebo-controlled trial. Fertil Steril 2004;82:878–84.
Adamson GD. Diagnosis and clinical presentation of endometriosis. Am J Obstet Gynecol 1990;162:568–9.
Afshar Y, Hastings J, Roqueiro D, Jeong JW, Giudice LC, Fazleabas AT. Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis. Biol Reprod 2013;88:44.
Akiyama Y, Yao JR, Kreder KJ, O'Donnell MA, Lutgendorf SK, Lyu D, Maeda D, Kume H, Homma Y, Luo Y. Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis. Am J Physiol Renal Physiol 2021;320:F174–F182.
Anjum AD, Payne LN, Appleby EC. Spontaneous occurrence and experimental induction of leiomyoma of the ventral ligament of the oviduct of the hen. Res Vet Sci 1988;45:341–8.
Arici A, Seli E, Zeyneloglu HB, Senturk LM, Oral E, Olive DL. Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor. J Clin Endocrinol Metab 1998;83:1201–5.
Attar E, Tokunaga H, Imir G, Yilmaz MB, Redwine D, Putman M, Gurates B, Attar R, Yaegashi N, Hales DB, Bulun SE. Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab 2009;94:623–31.
Awad-Igbaria Y, Edelman D, Ianshin E, Abu-Ata S, Shamir A, Bornstein J, Palzur E. Inflammation-induced mast cell-derived nerve growth factor: a key player in chronic vulvar pain? Brain 2025;148:331–46.
Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 2003;188:100–7.
Baldi A, Lanza A, Menicagli F, Signorile PG, Spugnini EP. Histological and immunohistochemical characterization of a case of endometriosis in a Guinea pig (Cavia tschudii). Case Rep Vet Med 2017;2017:4594510.
Ballard KD, Seaman HE, de Vries CS, Wright JT. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study—part 1. BJOG 2008;115:1382–91.
Bao H, Cong J, Qu Q, He S, Zhao D, Zhao H, Yin S, Ma D. Rosiglitazone alleviates LPS-induced endometritis via suppression of TLR4-mediated NF-kappaB activation. PLoS One 2024;19:e0280372.
Barrier BF, Allison J, Hubbard GB, Dick EJ Jr, Brasky KM, Schust DJ. Spontaneous adenomyosis in the chimpanzee (pan troglodytes): a first report and review of the primate literature: case report. Hum Reprod 2007;22:1714–7.
Barrier BF, Bates GW, Leland MM, Leach DA, Robinson RD, Propst AM. Efficacy of anti-tumor necrosis factor therapy in the treatment of spontaneous endometriosis in baboons. Fertil Steril 2004;81:775–9.
Baskin GB, Smith SM, Marx PA. Endometrial hyperplasia, polyps, and adenomyosis associated with unopposed estrogen in rhesus monkeys (Macaca mulatta). Vet Pathol 2002;39:572–5.
Bergeron S, Reed BD, Wesselmann U, Bohm-Starke N. Vulvodynia. Nat Rev Dis Primers 2020;6:36.
Bornstein J, Goldschmid N, Sabo E. Hyperinnervation and mast cell activation may be used as histopathologic diagnostic criteria for vulvar vestibulitis. Gynecol Obstet Invest 2004;58:171–8.
Bornstein J, Palzur E, Swash M, Petros P. Vulvodynia: a neuroinflammatory pain syndrome originating in pelvic visceral nerve plexuses due to mechanical factors. Arch Gynecol Obstet 2022;306:1411–5.
Cardaillac C, Levesque A, Riant T, Mortier A, Neunlist M, Perrouin-Verbe MA, Volteau C, Thubert T, Brochard C, Ploteau S. Evaluation of a scoring system for the detection of central sensitization among women with chronic pelvic pain. Am J Obstet Gynecol 2023;229:530.e1–530.e17.
Castro J, Harrington AM, Chegini F, Matusica D, Spencer NJ, Brierley SM, Haberberger RV, Barry CM. Clodronate treatment prevents vaginal hypersensitivity in a mouse model of Vestibulodynia. Front Cell Infect Microbiol 2022;11:784972.
Chakrabarty A, Liao Z, Mu Y, Smith PG. Inflammatory renin-angiotensin system disruption attenuates sensory hyperinnervation and mechanical hypersensitivity in a rat model of provoked vestibulodynia. The J Pain 2018;19:264–77.
Chan WY, Hill JC. Determination of menstrual prostaglandin levels in non-dysmenorrheic and dysmenorrheic subjects. Prostaglandins 1978;15:365–75.
Chapron C, Vannuccini S, Santulli P, Abrão MS, Carmona F, Fraser IS, Gordts S, Guo SW, Just PA, Noël JC, Pistofidis G, Van den Bosch T, Petraglia F. Diagnosing adenomyosis: an integrated clinical and imaging approach. Hum Reprod Update 2020;26:392–411.
Chavda V, Joshi B, Bhatt AD, Patel S, Savaliya M, Chaurasia B. Persistent pelvic pain in women: unraveling diagnostic challenges and the overlooked role of pelvic congestion syndrome. Ann Med Surg 2025;87:7950–2.
Chen Q, Li YW, Wang S, Fan QB, Shi HH, Leng JH, Sun DW, Lang JH, Zhu L. Clinical manifestations of adenomyosis patients with or without pain symptoms. J Pain Res 2019;12:3127–33.
Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, Chou TY, Liu YN, Chao KC, Yang MH. Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis. J Pathol 2010;222:261–70.
Chiang YF, Hung HC, Chen HY, Huang KC, Lin PH, Chang JY, Huang TC, Hsia SM. The inhibitory effect of extra virgin olive oil and its active compound oleocanthal on prostaglandin-induced uterine hypercontraction and pain-ex vivo and in vivo study. Nutrients 2020;12.3012.
Cianciolo RE, Butler SD, Eggers JS, Dick EJ Jr, Leland MM, de la Garza M, Brasky KM, Cummins LB, Hubbard GB. Spontaneous neoplasia in the baboon (papio spp.). J Med Primatol 2007;36:61–79.
Clemenza S, Vannuccini S, Capezzuoli T, Meleca CI, Pampaloni F, Petraglia F. Is primary dysmenorrhea a precursor of future endometriosis development? Gynecol Endocrinol 2021;37:287–93.
Cohen J, Naoura I, Castela M, Von N'Guyen T, Oster M, Fontaine R, Chabbert-Buffet N, Darai E, Aractingi S. Pregnancy affects morphology of induced endometriotic lesions in a mouse model through alteration of proliferation and angiogenesis. Eur J Obstet Gynecol Reprod Biol 2014;183:70–7.
Cook AL, Rogers TD, Sowers M. Spontaneous uterine leiomyosarcoma in a rhesus macaque. Contemp Top Lab Anim Sci 2004;43:47–9.
Craft RM, Mogil JS, Aloisi AM. Sex differences in pain and analgesia: the role of gonadal hormones. Eur J Pain 2004;8:397–411.
Cummings AM, Metcalf JL. Induction of endometriosis in mice: a new model sensitive to estrogen. Reprod Toxicol 1995;9:233–8.
D'Hooghe TM, Bambra CS, Cornillie FJ, Isahakia M, Koninckx PR. Prevalence and laparoscopic appearance of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus). Biol Reprod 1991;45:411–6.
D'Hooghe TM, Kyama CM, Chai D, Fassbender A, Vodolazkaia A, Bokor A, Mwenda JM. Nonhuman primate models for translational research in endometriosis. Reprod Sci 2009;16:152–61.
D'Hooghe TM, Nugent NP, Cuneo S, Chai DC, Deer F, Debrock S, Kyama CM, Mihalyi A, Mwenda JM. Recombinant human TNFRSF1A (r-hTBP1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug-controlled study. Biol Reprod 2006;74:131–6.
De Logu F, Boccella S, Guida F. Editorial: the role of neuroinflammation in chronic pain development and maintenance. Front Pharmacol 2021;12:821534.
De Logu F, Li Puma S, Landini L, Tuccinardi T, Poli G, Preti D, De Siena G, Patacchini R, Tsagareli MG, Geppetti P, Nassini R. The acyl-glucuronide metabolite of ibuprofen has analgesic and anti-inflammatory effects via the TRPA1 channel. Pharmacol Res 2019;142:127–39.
De Logu F, Marini M, Landini L, Souza Monteiro de Araujo D, Bartalucci N, Trevisan G, Bruno G, Marangoni M, Schmidt BL, Bunnett NW, Geppetti P, Nassini R. Peripheral nerve resident macrophages and schwann cells mediate cancer-induced pain. Cancer Res 2021;81:3387–401.
De Logu F, Nassini R, Hegron A, Landini L, Jensen DD, Latorre R, Ding J, Marini M, Souza Monteiro de Araujo D, Ramirez-Garcia P, Whittaker M, Retamal J, Titiz M, Innocenti A, Davis TP, Veldhuis N, Schmidt BL, Bunnett NW, Geppetti P. Schwann cell endosome CGRP signals elicit periorbital mechanical allodynia in mice. Nat Commun 2022;13:646.
De Logu F, Nassini R, Materazzi S, Carvalho Goncalves M, Nosi D, Rossi Degl'Innocenti D, Marone IM, Ferreira J, Li Puma S, Benemei S, Trevisan G, Souza Monteiro de Araujo D, Patacchini R, Bunnett NW, Geppetti P. Schwann cell TRPA1 mediates neuroinflammation that sustains macrophage-dependent neuropathic pain in mice. Nat Commun 2017;8:1887.
Di Girolamo G, Sanchez AJ, De Los Santos AR, Gonzalez CD. Is acetaminophen, and its combination with pamabrom, an effective therapeutic option in primary dysmenorrhoea? Expert Opin Pharmacother 2004;5:561–70.
Diaz I, Lumsden MA, Zeppernick M. Medical treatment of fibroids: FIGO best practice guidance. Int J Gynecol Obstet 2025;171:507–12.
Dick EJ Jr, Hubbard GB, Martin LJ, Leland MM. Record review of baboons with histologically confirmed endometriosis in a large established colony. J Med Primatol 2003;32:39–47.
DiGiacomo RF. Gynecologic pathology in the rhesus monkey (macaca mulatta). II. Findings in laboratory and free-ranging monkeys. Vet Pathol 1977;14:539–46.
Dolmans MM, Petraglia F, Catherino WH, Donnez J. Pathogenesis of uterine fibroids: current understanding and future directions. Fertil Steril 2024;122:6–11.
Donnez J, Stratopoulou CA, Dolmans MM. Endometriosis and adenomyosis: similarities and differences. Best Pract Res Clin Obstet Gynaecol 2024;92:102432.
Dorning A, Dhami P, Panir K, Hogg C, Park E, Ferguson GD, Hargrove D, Karras J, Horne AW, Greaves E. Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations. Dis Models Mech 2021;14:dmm049070.
Drosch M, Bullerdiek J, Zollner TM, Prinz F, Koch M, Schmidt N. A novel mouse model that closely mimics human uterine leiomyomas. Fertil Steril 2013;99:927–35.e6.
Elsherbini M, Koga K, Hiraoka T, Kumasawa K, Maki E, Satake E, Taguchi A, Makabe T, Takeuchi A, Izumi G, Takamura M, Harada M, Hirata T, Hirota Y, Wada-Hiraike O, Osuga Y. Establishment of a novel mouse model of adenomyosis suitable for longitudinal and quantitative analysis and perinatal outcome studies. Sci Rep 2022;12:17515.
Eschenbach DA, Wolner-Hanssen P, Hawes SE, Pavletic A, Paavonen J, Holmes KK. Acute pelvic inflammatory disease: associations of clinical and laboratory findings with laparoscopic findings. Obstet Gynecol 1997;89:184–92.
Everitt JI, Wolf DC, Howe SR, Goldsworthy TL, Walker C. Rodent model of reproductive tract leiomyomata. Clinical and pathological features. Am J Pathol 1995;146:1556–67.
Falsetta ML, Maddipati KR, Honn KV. Inflammation, lipids, and pain in vulvar disease. Pharmacol Ther 2023;248:108467.
Fan L, Liu Z, Zhang Z, Li T, Li H, Chen J, Zong X, Zhang X, Chen X, Bai H, Wang F, Shang C. Identifying the clinical presentations, progression, and sequela of pelvic inflammatory disease through physiological, histological and ultrastructural evaluation of a rat animal model. Ann Transl Med 2021;9:1710.
Farmer MA, Taylor AM, Bailey AL, Tuttle AH, MacIntyre LC, Milagrosa ZE, Crissman HP, Bennett GJ, Ribeiro-da-Silva A, Binik YM, Mogil JS. Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia. Sci Transl Med 2011;3:101ra191.
Fattori V, Franklin NS, Gonzalez-Cano R, Peterse D, Ghalali A, Madrian E, Verri WA Jr, Andrews N, Woolf CJ, Rogers MS. Nonsurgical mouse model of endometriosis-associated pain that responds to clinically active drugs. PAIN 2020;161:1321–31.
Ferries-Rowe E, Corey E, Archer JS. Primary dysmenorrhea: diagnosis and therapy. Obstet Gynecol 2020;136:1047–58.
Fiçicioğlu C, Tekin HI, Arioğlu PF, Okar I. A murine model of adenomyosis: the effects of hyperprolactinemia induced by fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, on adenomyosis induction in wistar albino rats. Acta Eur Fertil 1995;26:75–9.
Field KJ, Griffith JW, Lang CM. Spontaneous reproductive tract leiomyomas in aged guinea-pigs. J Comp Pathol 1989;101:287–94.
Fritsch M, Schmidt N, Groticke I, Frisk AL, Keator CS, Koch M, Slayden OD. Application of a patient derived xenograft model for predicative study of uterine fibroid disease. PLoS One 2015;10:e0142429.
Gao S, Gao Y, Cai L, Qin R. Luteolin attenuates staphylococcus aureus-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway. Microbiol Spectr 2024;12:e0327923.
Gelberg HB, McEntee K. Pathology of the canine and feline uterine tube. Vet Pathol 1986;23:770–5.
Gemesi TS, Lum D, Atashroo D, Chao L. Minimally invasive and ablative therapies for symptomatic uterine fibroids: a narrative review. Curr Opin Obstet Gynecol 2025;37:346–52.
Ghant MS, Sengoba KS, Recht H, Cameron KA, Lawson AK, Marsh EE. Beyond the physical: a qualitative assessment of the burden of symptomatic uterine fibroids on women's emotional and psychosocial health. J Psychosom Res 2015;78:499–503.
Giudice LC. Clinical practice. Endometriosis. N Engl J Med 2010;362:2389–98.
Giuliani E, As-Sanie S, Marsh EE. Epidemiology and management of uterine fibroids. Int J Gynecol Obstet 2020;149:3–9.
Goetsch MF, Morgan TK, Korcheva VB, Li H, Peters D, Leclair CM. Histologic and receptor analysis of primary and secondary vestibulodynia and controls: a prospective study. Am J Obstet Gynecol 2010;202:614.e1–614.e8.
Greaves E, Cousins FL, Murray A, Esnal-Zufiaurre A, Fassbender A, Horne AW, Saunders PT. A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium. Am J Pathol 2014;184:1930–9.
Greaves P, White IN. Experimental adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006;20:503–10.
Halbedl H, Pfabigan DM, Ebhardt I, Trutnovsky G. Mindfulness-based body scan training in multimodal physiotherapy for vulvodynia—a randomized controlled feasibility study. J Psychosom Obstet Gynecol 2025;46:2531057.
Hassan MH, Eyzaguirre E, Arafa HM, Hamada FM, Salama SA, Al-Hendy A. Memy I: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice. Am J Obstet Gynecol 2008;199:156.e1–156.e8.
Hayashi S, Nakamura T, Motooka Y, Ito F, Jiang L, Akatsuka S, Iwase A, Kajiyama H, Kikkawa F, Toyokuni S. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Redox Biol 2020;37:101726.
Hong DG, Hwang SM, Park JM. Efficacy of ganglion impar block on vulvodynia: case series and results of mid- and long-term follow-up. Medicine (Baltimore) 2021;100:e26799.
Huang TS, Chen YJ, Chou TY, Chen CY, Li HY, Huang BS, Tsai HW, Lan HY, Chang CH, Twu NF, Yen MS, Wang PH, Chao KC, Lee CC, Yang MH. Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells. J Cell Mol Med 2014;18:1358–71.
Iacovides S, Avidon I, Baker FC. What we know about primary dysmenorrhea today: a critical review. Hum Reprod Update 2015;21:762–78.
Ishikawa H, Ishi K, Serna VA, Kakazu R, Bulun SE, Kurita T. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology 2010;151:2433–42.
Islam EA, Shaik-Dasthagirisaheb Y, Kaushic C, Wetzler LM, Gray-Owen SD. The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice. Mucosal Immunol 2016;9:1051–64.
Jesuino F, Reis JP, Whitaker JCP, Campos A, Pastor MVD, Cechinel Filho V, Quintao NLM. Effect of synadenium grantii and its isolated compound on dysmenorrhea behavior model in mice. Inflammopharmacology 2019;27:613–20.
Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology 2018;129:343–66.
Jossens MO, Sweet RL. Pelvic inflammatory disease: risk factors and microbial etiologies. J Obstet Gynecol Neonatal Nurs 1993;22:169–79.
Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiologic Rev 2014;36:104–13.
Kanellopoulos D, Karagianni D, Pergialiotis V, Nikiteas N, Lazaris AC, Iliopoulos D. The effect of endometriosis on fertility in an animal model. J Med Life 2022;15:1170–5.
Kaspareit J, Friderichs-Gromoll S, Buse E, Habermann G. Spontaneous neoplasms observed in cynomolgus monkeys (Macaca fascicularis) during a 15-year period. Exp Toxicol Pathol 2007;59:163–9.
Keogh E, Attridge N, Walsh J, Bartlett J, Francis R, Bultitude JH, Eccleston C. Attentional biases towards body expressions of pain in men and women. J Pain 2021;22:1696–708.
Keppel Hesselink JM, Kopsky DJ, Sajben N. New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells. J Pain Res 2016;9:757–62.
Kim DJ, Ki YJ, Jang BH, Kim S, Kim SH, Jung KT. Clinically relevant concentrations of dexmedetomidine May reduce oxytocin-induced myometrium contractions in pregnant rats. Anesth Pain Med (Seoul) 2020;15:451–8.
Kirsch E, Rahman S, Kerolus K, Hasan R, Kowalska DB, Desai A, Bergese SD. Dysmenorrhea, a narrative review of therapeutic options. J Pain Res 2024;17:2657–66.
Kiviat NB, Wolner-Hanssen P, Eschenbach DA, Wasserheit JN, Paavonen JA, Bell TA, Critchlow CW, Stamm WE, Moore DE, Holmes KK. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis. Am J Surg Pathol 1990;14:167–75.
Lamvu G, Carrillo J, Ouyang C, Rapkin A. Chronic pelvic pain in women: a review. JAMA 2021;325:2381–91.
Landini L, Marini M, Souza Monteiro de Araujo D, Romitelli A, Montini M, Albanese V, Titiz M, Innocenti A, Bianchini F, Geppetti P, Nassini R, De Logu F. Schwann cell insulin-like growth factor receptor type-1 mediates metastatic bone cancer pain in mice. Brain Behav Immun 2023;110:348–64.
Landry J, Martinov T, Mengistu H, Dhanwada J, Benck CJ, Kline J, Boo B, Swanson L, Tonc E, Daughters R, Fife BT, Chatterjea D. Repeated hapten exposure induces persistent tactile sensitivity in mice modeling localized provoked vulvodynia. PLoS One 2017;12:e0169672.
Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009;10:895–926.
Latthe P, Latthe M, Say L, Gulmezoglu M, Khan KS. WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health 2006;6:177.
Lee SE, Greenough EK, Oancea P, Scheinfeld AR, Douglas AM, Gaudet AD. Sex differences in pain: spinal cord injury in female and Male mice elicits behaviors related to neuropathic pain. J Neurotrauma 2023;40:833–44.
Li Z, Shi L, Li Q, Zhao J, Lu W, Wang J. The expression and bioinformatics analysis of circular RNAs in endometritis mouse uterus tissues. Molecules 2022;27:3682.
Long CT, Luong RH, McKeon GP, Albertelli M. Uterine leiomyoma in a Guyanese squirrel monkey (Saimiri sciureus sciureus). J Am Assoc Lab Anim Sci 2010;49:226–30.
Machado SA, Bahr JM, Hales DB, Braundmeier AG, Quade BJ, Nowak RA. Validation of the aging hen (gallus Gallus domesticus) as an animal model for uterine leiomyomas. Biol Reprod 2012;87:86.
MacKenzie WF, Casey HW. Animal model of human disease. Endometriosis. Animal model: endometriosis in rhesus monkeys. Am J Pathol 1975;80:341–4.
Marquardt RM, Jeong JW, Fazleabas AT. Animal models of adenomyosis. Semin Reprod Med 2020;38:168–78.
Maruo T, Laoag-Fernandez JB, Pakarinen P, Murakoshi H, Spitz IM, Johansson E. Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium. Hum Reprod 2001;16:2103–8.
McEntee K, Nielsen SW. Tumours of the female genital tract. Bull World Health Organ 1976;53:217–26.
Mendiratta V, Lentz GM. 35—primary and secondary dysmenorrhea, premenstrual syndrome, and premenstrual dysphoric disorder: etiology, diagnosis, management. In: Gershenson DM, Lentz GM, Valea FA, Lobo RA, editors. Comprehensive gynecology. 8th ed. St. Louis: Elsevier, 2022. pp. 768–80.e764.
Mori T, Nagasawa H, Takahashi S. The induction of adenomyosis in mice by intrauterine pituitary isografts. Life Sci 1981;29:1277–82.
Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis. Eur J Obstet Gynecol Reprod Biol 2017;209:8–13.
Mozzachio K, Linder K, Dixon D. Uterine smooth muscle tumors in potbellied pigs (sus scrofa) resemble human fibroids: a potential animal model. Toxicol Pathol 2004;32:402–7.
Nagasawa H, Naito T. Enhanced potentials for mammary tumourigenesis and uterine adenomyosis in (SLN x C3H/He)F1 virgin mice. Lab Anim 1992;26:23–4.
Nie J, Liu X, Guo SW. Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis. Am J Obstet Gynecol 2010;202:346.e1–346.e8.
Oh SJ, Shin JH, Kim TH, Lee HS, Yoo JY, Ahn JY, Broaddus RR, Taketo MM, Lydon JP, Leach RE, Lessey BA, Fazleabas AT, Lim JM, Jeong JW. β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition. J Pathol 2013;231:210–22.
Oh Y, Lee J, Kim HC, Hahn TW, Yoon BI, Han JH, Kwon YS, Park JJ, Koo DB, Rhee KJ, Jung BD. Establishment of hydrochloric acid/lipopolysaccharide-induced pelvic inflammatory disease model. J Vet Sci 2016;17:413–9.
Park KS, Park KI, Hwang DS, Lee JM, Jang JB, Lee CH. A review of in vitro and in vivo studies on the efficacy of herbal medicines for primary dysmenorrhea. Evid Based Complement Altern Med 2014;2014:296860.
Patton DL, Cosgrove Sweeney YT, Paul KJ. A summary of preclinical topical microbicide vaginal safety and chlamydial efficacy evaluations in a pigtailed macaque model. Sex Transm Dis 2008;35:889–97.
Patton DL, Kuo CC, Wang SP, Halbert SA. Distal tubal obstruction induced by repeated Chlamydia trachomatis salpingeal infections in pig-tailed macaques. J Infect Dis 1987;155:1292–9.
Patton DL, Sweeney YT, Stamm WE. Significant reduction in inflammatory response in the macaque model of chlamydial pelvic inflammatory disease with azithromycin treatment. J Infect Dis 2005;192:129–35.
Patton DL, Wølner-Hanssen P, Cosgrove SJ, Holmes KK. The effects of Chlamydia trachomatis on the female reproductive tract of the Macaca nemestrina after a single tubal challenge following repeated cervical inoculations. Obstet Gynecol 1990;76:643–50.
Peitsidis P, Koukoulomati A. Tranexamic acid for the management of uterine fibroid tumors: a systematic review of the current evidence. World J Clin Cases 2014;2:893–8.
Peng Y, Zheng X, Fan Z, Zhou H, Zhu X, Wang G, Liu Z. Paeonol alleviates primary dysmenorrhea in mice via activating CB2R in the uterus. Phytomedicine 2020;68:153151.
Peregrino PFM, Messina ML, Menezes MR, Júnior JMS, Cerri GG, Baracat EC. Magnetic resonance-guided focused ultrasound for uterine fibroids. Clinics (Sao Paulo) 2025;80:100603.
Porpora MG, Koninckx PR, Piazze J, Natili M, Colagrande S, Cosmi EV. Correlation between endometriosis and pelvic pain. J Am Assoc Gynecol Laparosc 1999;6:429–34.
Proctor M, Farquhar C. Diagnosis and management of dysmenorrhoea. BMJ 2006;332:1134–8.
Reed BD, Caron AM, Gorenflo DW, Haefner HK. Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors. J Lower Genital Tract Dis 2006;10:245–51.
Romagnolo B, Molina T, Leroy G, Blin C, Porteux A, Thomasset M, Vandewalle A, Kahn A, Perret C. Estradiol-dependent uterine leiomyomas in transgenic mice. J Clin Invest 1996;98:777–84.
Ross J, Guaschino S, Cusini M, Jensen J. 2017 European guideline for the management of pelvic inflammatory disease. Int J STD AIDS 2018;29:108–14.
Ryan A, Healey M, Cheng C, Dior U, Reddington C. Central sensitisation in pelvic pain: a cohort study. Aust N Z J Obstet Gynaecol 2022;62:868–74.
Sadownik LA. Etiology, diagnosis, and clinical management of vulvodynia. Int J Womens Health 2014;6:437–49.
Sammour A, Pirwany I, Usubutun A, Arseneau J, Tulandi T. Correlations between extent and spread of adenomyosis and clinical symptoms. Gynecol Obstet Invest 2002;54:213–6.
Santulli P, Vannuccini S, Bourdon M, Chapron C, Petraglia F. Adenomyosis: the missed disease. Reprod Biomed Online 2025;50:104837.
Savaris RF, Fuhrich DG, Maissiat J, Duarte RV, Ross J. Antibiotic therapy for pelvic inflammatory disease. Cochrane Database Syst Rev 2020;8:CD010285.
Schmauss C, Yaksh TL. In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. J Pharmacol Exp Ther 1984;228:1–12.
Schroll JB, Black AY, Farquhar C, Chen I. Combined oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev 2023;7:CD002120.
Shakiba K, Bena JF, McGill KM, Minger J, Falcone T. Surgical treatment of endometriosis: a 7-year follow-up on the requirement for further surgery. Obstet Gynecol 2008;111:1285–92.
Sharma H, Ji E, Yap P, Vilimas P, Kyloh M, Spencer NJ, Haberberger RV, Barry CM. Innervation changes induced by inflammation in the Murine vagina. Neuroscience 2018;372:16–26.
Simitsidellis I, Gibson DA, Saunders PTK. Animal models of endometriosis: replicating the aetiology and symptoms of the human disorder. Best Pract Res Clin Endocrinol Metab 2018;32:257–69.
Somigliana E, Viganò P, Rossi G, Carinelli S, Vignali M, Panina-Bordignon P. Endometrial ability to implant in ectopic sites can be prevented by interleukin-12 in a murine model of endometriosis. Hum Reprod 1999;14:2944–50.
Spoelstra SK, Borg C, Weijmar Schultz WC. Anticonvulsant pharmacotherapy for generalized and localized vulvodynia: a critical review of the literature. J Psychosom Obstet Gynecol 2013;34:133–8.
Stewart EA, Laughlin-Tommaso SK, Catherino WH, Lalitkumar S, Gupta D, Vollenhoven B. Uterine fibroids. Nat Rev Dis Primers 2016;2:16043.
Stöcklin-Gautschi NM, Guscetti F, Reichler IM, Geissbühler U, Braun SA, Arnold S. Identification of focal adenomyosis as a uterine lesion in two dogs. J Small Anim Pract 2001;42:413–6.
Stringer EM, De Voe RS, Valea F, Toma S, Mulvaney G, Pruitt A, Troan B, Loomis MR. Medical and surgical management of reproductive neoplasia in two western lowland gorillas (gorilla gorilla gorilla). J Med Primatol 2010;39:328–35.
Suzuki Y, Ii M, Saito T, Terai Y, Tabata Y, Ohmichi M, Asahi M. Establishment of a novel mouse xenograft model of human uterine leiomyoma. Sci Rep 2018;8:8872.
Suzuki-Kakisaka H, Murakami T, Hirano T, Terada Y, Yaegashi N, Okamura K. Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice. Fertil Steril 2008;90:1523–7.
Tanwar PS, Lee HJ, Zhang L, Zukerberg LR, Taketo MM, Rueda BR, Teixeira JM. Constitutive activation of beta-catenin in uterine stroma and smooth muscle leads to the development of mesenchymal tumors in mice. Biol Reprod 2009;81:545–52.
Titiz M, Landini L, Souza Monteiro de Araujo D, Marini M, Seravalli V, Chieca M, Pensieri P, Montini M, De Siena G, Pasquini B, Vannuccini S, Iannone LF, Cunha TM, Brancolini G, Bellantoni E, Scuffi I, Mastricci A, Tesi M, Di Tommaso M, Petraglia F, Geppetti P, Nassini R, De Logu F. Schwann cell C5aR1 co-opts inflammasome NLRP1 to sustain pain in a mouse model of endometriosis. Nat Commun 2024;15:10142.
Tuo L, Tang S, Li S, Gu S, Xie Z. Murine models and research progress on dysmenorrhea. Reprod Sci 2023;30:2362–72.
Tympanidis P, Terenghi G, Dowd P. Increased innervation of the vulval vestibule in patients with vulvodynia. Br J Dermatol 2003;148:1021–7.
Van Voorhis WC, Barrett LK, Sweeney YT, Kuo CC, Patton DL. Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes produces a Th1-like cytokine response associated with fibrosis and scarring. Infect Immun 1997;65:2175–82.
Vannuccini S, Petraglia F, Carmona F, Calaf J, Chapron C. The modern management of uterine fibroids-related abnormal uterine bleeding. Fertil Steril 2024;122:20–30.
Wang J, Doan LV. Clinical pain management: current practice and recent innovations in research. Cell Rep Med 2024;5:101786.
Wei A, Feng H, Jia XM, Tang H, Liao YY, Li BR. Ozone therapy ameliorates inflammation and endometrial injury in rats with pelvic inflammatory disease. Biomed Pharmacother 2018;107:1418–25.
Willets JM, Brighton PJ, Mistry R, Morris GE, Konje JC, Challiss RA. Regulation of oxytocin receptor responsiveness by G protein-coupled receptor kinase 6 in human myometrial smooth muscle. Mol Endocrinol 2009;23:1272–80.
Wilson MR, Holladay J, Chandler RL. A mouse model of endometriosis mimicking the natural spread of invasive endometrium. Hum Reprod 2020;35:58–69.
Wolner-Hanssen P, Patton DL, Holmes KK. Protective immunity in pig-tailed macaques after cervical infection with Chlamydia trachomatis. Sex Transm Dis 1991;18:21–5.
Wong J, Chiang YF, Shih YH, Chiu CH, Chen HY, Shieh TM, Wang KL, Huang TC, Hong YH, Hsia SM, Salvia sclarea L. Essential oil extract and its antioxidative phytochemical sclareol inhibit oxytocin-induced uterine hypercontraction dysmenorrhea model by inhibiting the Ca(2+)-MLCK-MLC20 signaling Cascade: an Ex vivo and in vivo study. Antioxidants (Basel) 2020;9:10.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. PAIN 2011;152:S2-s15.
Xie AX, Iguchi N, Clarkson TC, Malykhina AP. Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain. PLoS One 2022;17:e0262769.
Xu C, Long A, Fang X, Wood SL, Slater DM, Ni X, Olson DM. Effects of PGF2α on the expression of uterine activation proteins in pregnant human myometrial cells from upper and lower segment. J Clin Endocrinol Metab 2013;98:2975–83.
Yang L, Cao Z, Yu B, Chai C. An in vivo mouse model of primary dysmenorrhea. Exp Anim 2015;64:295–303.
Young M, Mikes BA. Uterine fibroid embolization. Treasure Island: StatPearls, 2025.
Yuan C, Liu L, Zhao Y, Wang K. Puerarin inhibits staphylococcus aureus-induced endometritis through attenuating inflammation and ferroptosis via regulating the P2X7/NLRP3 signalling pathway. J Cell Mol Med 2024;28:e18550.
Yusuf H, Trent M. Management of pelvic inflammatory disease in clinical practice. Ther Clin Risk Manage 2023;19:183–92.
Zhai J, Vannuccini S, Petraglia F, Giudice LC. Adenomyosis: mechanisms and pathogenesis. Semin Reprod Med 2020;38:129–43.
Zhang H, Wu ZM, Yang YP, Shaukat A, Yang J, Guo YF, Zhang T, Zhu XY, Qiu JX, Deng GZ, Shi DM. Catalpol ameliorates LPS-Induced endometritis by inhibiting inflammation and TLR4/NF-kappaB signaling. J Zhejiang Univ Sci B 2019;20:816–27.
Zhou S, Yi T, Liu R, Bian C, Qi X, He X, Wang K, Li J, Zhao X, Huang C, Wei Y. Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis. Mol Cell Proteomics 2012;11:M112.017988-1–M112.017988-24.
Zhu B, Zhang C, Shen X, Chen C, Chen X, Lu Y, Chen Y, Guo M. Protective effects of resveratrol against adenomyosis in a mouse model. Dose Response 2023;21:15593258231164055.
Grant Information: IG 2020-ID 24503 Fondazione Italiana per la Ricerca sul Cancro; FIS-2023-03323 Fondo Italiano per la Scienza
Contributed Indexing: Keywords: Adenomyosis; Dysmenorrhea; Endometriosis; Pain; Pelvic inflammatory disease; Sex; Uterine leiomyomas; Vulvodynia; Women
Entry Date(s): Date Created: 20260529 Date Completed: 20260720 Latest Revision: 20260726
Update Code: 20260726
PubMed Central ID: PMC13382874
DOI: 10.1097/j.pain.0000000000004016
PMID: 42212477
Database: MEDLINE
Description
ISSN:1872-6623
DOI:10.1097/j.pain.0000000000004016