山东大学学报 (医学版) ›› 2025, Vol. 63 ›› Issue (10): 1-7.doi: 10.6040/j.issn.1671-7554.0.2024.0943
• 重点专题——子宫内膜异位症相关疼痛 • 下一篇
徐萍,张信美
XU Ping, ZHANG Xinmei
摘要: 子宫内膜异位症(内异症)是一种常见于生育年龄女性的慢性炎症性疾病,累及多器官系统且为雌激素依赖性疾病。70%~80%的患者以疼痛为主要症状,根据病灶累及部位,疼痛分别表现为痛经、性交痛、排尿排便痛、非经期慢性盆腔疼痛等。内异症疼痛的机制错综复杂且涉及多条交互作用的路径,一直是研究的热点。目前主要认为下丘脑-垂体-性腺轴、自身免疫炎症系统、外周/中枢神经系统这三大系统的交互作用,导致疼痛持续加剧及痛觉过敏。下丘脑-垂体-性腺轴释放雌激素促进内异症病灶生长,刺激外周伤害性感受器激活感觉神经纤维,进而触发自身免疫系统的巨噬细胞及肥大细胞等分泌炎症因子及致痛因子,最终导致周围神经及中枢神经系统敏化,神经系统激活后正反馈释放P物质、降钙素基因相关肽等因子持续激活免疫系统,导致持续敏化及交叉敏化,疼痛加剧。
中图分类号:
| [1] McNamara HC, Frawley HC, Donoghue JF, et al. Peripheral, central, and cross sensitization in endometriosis-associated pain and comorbid pain syndromes[J]. Front Reprod Health, 2021, 3: 729642. doi: 10.3389/frph.2021.729642 [2] Gruber TM, Mechsner S. Pathogenesis of endometriosis: the origin of pain and subfertility[J]. Cells, 2021, 10(6): 1381. doi: 10.3390/cells10061381 [3] Mechsner S. Endometriosis: an often unrecognized pain disorder[J]. Schmerz, 2016, 30(5): 477-490. [4] Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: a committee opinion[J]. Fertil Steril, 2014, 101(4): 927-935. [5] Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist[J]. N Engl J Med, 2017, 377(1): 28-40. [6] Chen YX, Li T. Unveiling the mechanisms of pain in endometriosis: comprehensive analysis of inflammatory sensitization and therapeutic potential[J]. Int J Mol Sci, 2025, 26(4): 1770. [7] Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications[J]. Hum Reprod Update, 2005, 11(6): 595-606. [8] Zigmond RE, Echevarria FD. Macrophage biology in the peripheral nervous system after injury[J]. Prog Neurobiol, 2019, 173: 102-121. doi: 10.1016/j.pneurobio.2018.12.001 [9] Gheorghe RO, Grosu AV, Bica-Popi M, et al. The Yin/Yang balance of communication between sensory neurons and macrophages in traumatic peripheral neuropathic pain[J]. Int J Mol Sci, 2022, 23(20): 12389. doi: 10.3390/ijms232012389 [10] Lamceva J, Uljanovs R, Strumfa I. The main theories on the pathogenesis of endometriosis[J]. Int J Mol Sci, 2023, 24(5): 4254. [11] Yao CC, Narumiya S. Prostaglandin-cytokine crosstalk in chronic inflammation[J]. Br J Pharmacol, 2019, 176(3): 337-354. [12] Wei YJ, Liang YC, Lin HS, et al. Autonomic nervous system and inflammation interaction in endometriosis-associated pain[J]. J Neuroinflammation, 2020, 17(1): 80. doi: 10.1186/s12974-020-01752-1 [13] Machairiotis N, Vasilakaki S, Thomakos N. Inflammatory mediators and pain in endometriosis: a systematic review[J]. Biomedicines, 2021, 9(1): 54. doi: 10.3390/biomedicines9010054 [14] Binda MM, Donnez J, Dolmans MM. Targeting mast cells: a new way to treat endometriosis[J]. Expert Opin Ther Targets, 2017, 21(1): 67-75. [15] Yu J, Francisco AMC, Patel BG, et al. IL-1β stimulates brain-derived neurotrophic factor production in eutopic endometriosis stromal cell cultures: a model for cytokine regulation of neuroangiogenesis[J]. Am J Pathol, 2018, 188(10): 2281-2292. [16] Volpato LK, Horewicz VV, Bobinski F, et al. Annexin A1, FPR2/ALX, and inflammatory cytokine expression in peritoneal endometriosis[J]. J Reprod Immunol, 2018, 129: 30-35. doi: 10.1016/j.jri.2018.08.002 [17] Song SY, Jung YW, Shin W, et al. Endometriosis-related chronic pelvic pain[J]. Biomedicines, 2023, 11(10): 2868. [18] Pezet S, McMahon SB. Neurotrophins: mediators and modulators of pain[J]. Annu Rev Neurosci, 2006, 29: 507-538. doi: 10.1146/annurev.neuro.29.051605.112929 [19] Clower L, Fleshman T, Geldenhuys WJ, et al. Targeting oxidative stress involved in endometriosis and its pain[J]. Biomolecules, 2022, 12(8): 1055. doi: 10.3390/biom12081055 [20] Zubrzycka A, Migdalska-Sk M, Jdrzejczyk S, et al. The expression of TGF-β1, SMAD3, ILK and miRNA-21 in the ectopic and eutopic endometrium of women with endometriosis[J]. Int J Mol Sci, 2023, 24(3): 2453. [21] Arnold J, Barcena de Arellano ML, Rüster C, et al. Imbalance between sympathetic and sensory innervation in peritoneal endometriosis[J]. Brain Behav Immun, 2012, 26(1): 132-141. [22] Liang YC, Liu D, Yang F, et al. Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain[J]. J Pain Res, 2018, 11: 1999-2009. [23] Kaelberer MM, Buchanan KL, Klein ME, et al. A gut-brain neural circuit for nutrient sensory transduction[J]. Science, 2018, 361(6408): eaat5236. doi: 10.1126/science.aat5236 [24] Anaf V, Simon P, El Nakadi I, et al. Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis[J]. Hum Reprod, 2002, 17(7): 1895-1900. [25] Yu J, Berga SL, Zou E, et al. Neurotrophins and their receptors, novel therapeutic targets for pelvic pain in endometriosis, are coordinately regulated by IL-1β via the JNK signaling pathway[J]. Am J Pathol, 2023, 193(8): 1046-1058. [26] Rocha AL, Vieira EL, Ferreira MC, et al. Plasma brain-derived neurotrophic factor in women with pelvic pain: a potential biomarker for endometriosis?[J]. Biomark Med, 2017, 11(4): 313-317. [27] Godin SK, Wagner J, Huang P, et al. The role of peripheral nerve signaling in endometriosis[J]. FASEB Bioadv, 2021, 3(10): 802-813. [28] Bohonyi N, Pohóczky K, Szalontai B, et al. Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis[J]. Mol Pain, 2017, 13: 1744806917705564. doi: 10.1177/1744806917705564 [29] Kale A, Baydili KNS, Keles E, et al. Comparison of isolated sciatic nerve and sacral nerve root endometriosis: a review of the literature[J]. J Minim Invasive Gynecol, 2022, 29(8): 943-951. [30] Di Donna MC, Cucinella G, Sozzi G, et al. Surgical neuropelveology: lateral femoral cutaneous nerve endometriosis. laparoscopic resection and nerve transplantation[J]. J Minim Invasive Gynecol, 2021, 28(12): 1978-1979. [31] Li T, Mamillapalli R, Ding S, et al. Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice[J]. Biol Reprod, 2018, 99(2): 349-359. [32] As-Sanie S, Kim J, Schmidt-Wilcke T, et al. Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain[J]. J Pain, 2016, 17(1): 1-13. [33] De Blasio FM, Love S, Barry RJ, et al. Frontocentral delta-beta amplitude coupling in endometriosis-related chronic pelvic pain[J]. Clin Neurophysiol, 2023, 149: 146-156. doi: 10.1016/j.clinph.2023.02.173 [34] As-Sanie S, Harris RE, Napadow V, et al. Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study[J]. Pain, 2012, 153(6), 1006-1014. [35] Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: a review of pelvic and central nervous system mechanisms[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 51, 53-67. doi: 10.1016/j.bpobgyn.2018.01.014 [36] Bashir ST, Redden CR, Raj K, et al. Endometriosis leads to central nervous system-wide glial activation in a mouse model of endometriosis[J]. J Neuroinflammation, 2023, 20(1): 59. doi: 10.1186/s12974-023-02713-0 [37] Tirlapur SA, Kuhrt K, Chaliha C, et al. The ‘evil twin syndrome’ in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis[J]. Int J Surg, 2013, 11(3): 233-237. [38] Cheng C, Rosamilia A, Healey M. Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic pelvic pain: a prospective observational study[J]. Int Urogynecol J, 2012, 23(10): 1361-1366. [39] Schomacker ML, Hansen KE, Ramlau-Hansen CH, et al. Is endometriosis associated with irritable bowel syndrome? A cross-sectional study[J]. Eur J Obstet Gynecol Reprod Biol, 2018, 231: 65-69. doi: 10.1016/j.ejogrb.2018.10.023 [40] DiVasta AD, Zimmerman LA, Vitonis AF, et al. Overlap between irritable bowel syndrome diagnosis and endometriosis in adolescents[J]. Clin Gastroenterol Hepatol, 2021, 19(3): 528-537. [41] Smorgick N, Marsh CA, As-Sanie S, et al. Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis[J]. J Pediatr Adolesc Gynecol, 2013, 26(3): 171-175. [42] Graziottin A, Murina F, Gambini D, et al. Vulvar pain: the revealing scenario of leading comorbidities in 1183 cases[J]. Eur J Obstet Gynecol Reprod Biol, 2020, 252: 50-55. doi: 10.1016/j.ejogrb.2020.05.052 [43] Ge P, Ren JM, Harrington AM, et al. Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk[J]. Pain, 2019, 160(11): 2566-2579. [44] Jobling P, Graham BA, Brichta AM, et al. Cervix stimu-lation evokes predominantly subthreshold synaptic responses in mouse thoracolumbar and lumbosacral superficial dorsal horn neurons[J]. J Sex Med, 2010, 7(6): 2068-2076. [45] Chaban VV. Visceral sensory neurons that innervate both uterus and colon express nociceptive TRPv1 and P2X3 receptors in rats[J]. Ethn Dis, 2008, 18(Suppl 2): S2-20-S224. [46] Christianson JA, Liang RM, Ustinova EE, et al. Convergence of bladder and colon sensory innervation occurs at the primary afferent level[J]. Pain, 2007, 128(3): 235-243. [47] Berna C, Leknes S, Holmes EA, et al. Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness[J]. Biol Psychiatry, 2010, 67(11): 1083-1090. [48] Ploghaus A, Narain C, Beckmann CF, et al. Exacerbation of pain by anxiety is associated with activity in a hippocampal network[J]. J Neurosci, 2001, 21(24): 9896-9903. [49] Lorençatto C, Petta CA, Navarro MJ, et al. Depression in women with endometriosis with and without chronic pelvic pain[J]. Acta Obstet Gynecol Scand, 2006, 85(1):88-92. [50] Sepulcri RD, do Amaral VF. Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2009, 142(1): 53-56. [51] van Aken MAW, Oosterman JM, van Rijn CM, et al. Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment[J]. Fertil Steril, 2017, 108(4): 679-686. |
| [1] | 王建民,李晓峰,由志涛,董圣杰,赵宇驰,李占菊,邹德鑫,张剑锋,孙涛,杜伟. 基于可解释机器学习的后路腰椎椎体间融合术后慢性疼痛风险预测模型构建[J]. 山东大学学报 (医学版), 2026, 64(2): 78-88. |
| [2] | 宋轲,牟宗友,翟申浩,牛闯,郭亚琪,张腾腾,任雪冰,刘培来. 布比卡因脂质体在全膝关节置换术后的镇痛疗效[J]. 山东大学学报 (医学版), 2026, 64(2): 111-117. |
| [3] | 张舒淇,江延姣,印丹. 生殖道微生物与子宫内膜异位症发展之间的联系[J]. 山东大学学报 (医学版), 2025, 63(5): 120-126. |
| [4] | 周坤,刘婷,姜艳菊,胡泽楷,李宇佳,冯武仪,黄继莉,叶汪泉,赵小峰,胡军. 孟德尔随机化分析膝骨关节炎疼痛与肌力的因果关联[J]. 山东大学学报 (医学版), 2025, 63(11): 61-67. |
| [5] | 黄艳,周应芳,彭超. 青少年子宫内膜异位症的管理要点和策略[J]. 山东大学学报 (医学版), 2025, 63(10): 8-12. |
| [6] | 薛铭,梁静,凌斌. 各种类型子宫内膜异位症疼痛特点及治疗研究进展[J]. 山东大学学报 (医学版), 2025, 63(10): 13-19. |
| [7] | 赵书睿,赵烨. 围绝经期及绝经后期子宫内膜异位症的诊疗现状[J]. 山东大学学报 (医学版), 2025, 63(10): 20-26. |
| [8] | 梁炎春,严莹,麦华希,姚书忠. 地诺孕素在子宫内膜异位症相关性疼痛中的治疗作用:从基础到临床[J]. 山东大学学报 (医学版), 2025, 63(10): 27-33. |
| [9] | 董向毅,刘昕,刘欣欣,徐亚瑄,赵琳丽,陶国伟. 盆腔深部子宫内膜异位症的超声评价[J]. 山东大学学报 (医学版), 2025, 63(10): 34-42. |
| [10] | 刘振花,连雅囡,米国琳. 子宫内膜异位症疼痛的心理因素及干预措施的研究进展[J]. 山东大学学报 (医学版), 2025, 63(10): 43-51. |
| [11] | 杜煜晗,孙莹,杜惠兰. 红花如意丸对寒凝血瘀型子宫内膜异位症痛经患者疼痛的疗效及机制[J]. 山东大学学报 (医学版), 2025, 63(10): 52-60. |
| [12] | 卫嘉晟,杨保仲,魏伟,薛亚婷,崔臣龙,方俊. microRNA-210-3p通过调控TET2的表达抑制大鼠炎性疼痛[J]. 山东大学学报 (医学版), 2024, 62(6): 17-29. |
| [13] | 武姗姗,汪树仁,赵同航,张宗旺. 消化内镜手术术后疼痛分析:回顾性队列研究[J]. 山东大学学报 (医学版), 2024, 62(2): 42-50. |
| [14] | 王震,颜凤,宗孟至,徐峰,陈玉国,李传保. Turner综合征并发急性心肌梗死1例[J]. 山东大学学报 (医学版), 2024, 62(2): 109-112. |
| [15] | 牛雅文,李凤娇. PAR-2在烟曲霉菌感染的人角膜上皮细胞中的作用[J]. 山东大学学报 (医学版), 2024, 62(12): 96-101. |
|
||