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Unveil the pain of endometriosis: from the perspective of the nervous system

Published online by Cambridge University Press:  05 September 2022

Peiya Fan  and
Tian Li
Peiya Fan
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
Tian Li*
Affiliation:
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
*
Author for correspondence: Tian Li, E-mail: litian278@126.com
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Abstract

Endometriosis is a chronic inflammatory disease with pelvic pain and uncharacteristic accompanying symptoms. Endometriosis-associated pain often persists despite treatment of the disease, thus it brings a deleterious impact on their personal lives as well as imposing a substantial economic burden on them. At present, mechanisms underlie endometriosis-associated pain including inflammatory reaction, injury, aberrant blood vessels and the morphological and functional anomaly of the peripheral and central nervous systems. The nerve endings are influenced by the physical and chemical factors surrounding the lesion, via afferent nerve to the posterior root of the spinal nerve, then to the specific cerebral cortex involved in nociception. However, our understanding of the aetiology and mechanism of this complex pain process caused by endometriosis remains incomplete. Identifying the pathogenesis of endometriosis is crucial to disease management, offering proper treatment, and helping patients to seek novel targets for the maintenance and contributors of chronic pain. The main aim of this review is to focus on every possible mechanism of pain related to endometriosis in both peripheral and central nervous systems, and to present related mechanisms of action from the interaction between peripheral lesions and nerves to the changes in transmission of pain, resulting in hyperalgesia and the corresponding alterations in cerebral cortex and brain metabolism.

Keywords

Brainendometriosishyperalgesiamechanism of painneurogenesissensitisation
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e36
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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References

Chapron, C et al. (2019) Rethinking mechanisms, diagnosis and management of endometriosis. Nature Reviews. Endocrinology 15, 666–682.CrossRefGoogle ScholarPubMed
Shafrir, AL et al. (2018) Risk for and consequences of endometriosis: a critical epidemiologic review. Best Practice & Research. Clinical Obstetrics & Gynaecology 51, 1–15.CrossRefGoogle ScholarPubMed
Pascoal, E et al. (2022) Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research. Ultrasound in Obstetrics & Gynecology 60(3), 309–327.CrossRefGoogle ScholarPubMed
Zondervan, KT, Becker, CM and Missmer, SA (2020) Endometriosis. New England Journal of Medicine 382, 1244–1256.CrossRefGoogle ScholarPubMed
Lamvu, G et al. (2021) Chronic pelvic pain in women: a review. JAMA 325, 2381–2391.CrossRefGoogle ScholarPubMed
Wang, Y, Nicholes, K and Shih, IM (2020) The origin and pathogenesis of endometriosis. Annual Review of Pathology 15, 71–95.CrossRefGoogle ScholarPubMed
Leone Roberti Maggiore, U et al. (2017) Bladder endometriosis: a systematic review of pathogenesis, diagnosis, treatment, impact on fertility, and risk of malignant transformation. European Urology 71, 790–807.CrossRefGoogle ScholarPubMed
Becker, CM et al. (2022) ESHRE guideline: endometriosis. Human Reproduction Open 2022, hoac009.CrossRefGoogle ScholarPubMed
Taylor, HS, Kotlyar, AM and Flores, VA (2021) Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 397, 839–852.CrossRefGoogle ScholarPubMed
Maddern, J et al. (2020) Pain in endometriosis. Frontiers in Cellular Neuroscience 14, 590823.CrossRefGoogle ScholarPubMed
Liang, Y et al. (2018) Villainous role of estrogen in macrophage-nerve interaction in endometriosis. Reproductive Biology and Endocrinology: RB&E 16, 122.CrossRefGoogle ScholarPubMed
Gomes, FIF, Cunha, FQ and Cunha, TM (2020) Peripheral nitric oxide signaling directly blocks inflammatory pain. Biochemical Pharmacology 176, 113862.CrossRefGoogle ScholarPubMed
Fassbender, A et al. (2013) Biomarkers of endometriosis. Fertility and Sterility 99, 1135–1145.CrossRefGoogle ScholarPubMed
Wang, G et al. (2009) Rich innervation of deep infiltrating endometriosis. Human Reproduction 24, 827–834.CrossRefGoogle ScholarPubMed
Bokor, A et al. (2009) Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis. Human Reproduction 24, 3025–3032.CrossRefGoogle ScholarPubMed
Wang, G et al. (2010) Neuroendocrine cells in eutopic endometrium of women with endometriosis. Human Reproduction 25, 387–391.CrossRefGoogle ScholarPubMed
Terkelsen, AJ et al. (2017) The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes. The Lancet. Neurology 16, 934–944.CrossRefGoogle ScholarPubMed
Liang, Y et al. (2018) Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain. Journal of Pain Research 11, 1999–2009.CrossRefGoogle ScholarPubMed
McAllister, SL, Dmitrieva, N and Berkley, KJ (2012) Sprouted innervation into uterine transplants contributes to the development of hyperalgesia in a rat model of endometriosis. PLoS ONE 7, e31758.CrossRefGoogle Scholar
Tejada, MA et al. (2022) Identification of altered evoked and non-evoked responses in a heterologous mouse model of endometriosis-associated pain. Biomedicines 10, 501–515.CrossRefGoogle Scholar
Tokushige, N et al. (2006) High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis. Human Reproduction 21, 782–787.CrossRefGoogle ScholarPubMed
Ellett, L et al. (2015) Are endometrial nerve fibres unique to endometriosis? A prospective case-control study of endometrial biopsy as a diagnostic test for endometriosis in women with pelvic pain. Human Reproduction 30, 2808–2815.Google ScholarPubMed
May, KE et al. (2011) Endometrial alterations in endometriosis: a systematic review of putative biomarkers. Human Reproduction Update 17, 637–653.CrossRefGoogle ScholarPubMed
Zomer, MT et al. (2022) Assessment of nerve fiber density and expression of hormonal receptors within rectosigmoid endometriosis nodules. Journal of Minimally Invasive Gynecology 29, 265–273.CrossRefGoogle ScholarPubMed
Scheerer, C et al. (2017) Reduced sympathetic innervation in endometriosis is associated to semaphorin 3C and 3F expression. Molecular Neurobiology 54, 5131–5141.CrossRefGoogle ScholarPubMed
Barcena de Arellano, ML and Mechsner, S (2014) The peritoneum – an important factor for pathogenesis and pain generation in endometriosis. Journal of Molecular Medicine 92, 595–602.Google ScholarPubMed
Yilmaz, BD and Bulun, SE (2019) Endometriosis and nuclear receptors. Human Reproduction Update 25, 473–485.CrossRefGoogle ScholarPubMed
Jana, B et al. (2018) Long-term estradiol-17β exposure decreases the cholinergic innervation pattern of the pig ovary. Annals of Anatomy 216, 135–141.CrossRefGoogle ScholarPubMed
Ghersa, F et al. (2019) Reduced inflammatory state promotes reinnervation of endometriotic-like lesions in TNFRp55 deficient mice. Molecular Human Reproduction 25, 385–396.CrossRefGoogle ScholarPubMed
Benitez, A et al. (2021) Nerve growth factor: a dual activator of noradrenergic and cholinergic systems of the rat ovary. Frontiers in Endocrinology 12, 636600.CrossRefGoogle ScholarPubMed
Hao, M et al. (2021) Reduced vagal tone in women with endometriosis and auricular vagus nerve stimulation as a potential therapeutic approach. Scientific Reports 11, 1345.CrossRefGoogle ScholarPubMed
Yeater, TD et al. (2021) Chronic pain is associated with reduced sympathetic nervous system reactivity during simple and complex walking tasks: potential cerebral mechanisms. Chronic Stress 5, 24705470211030273.CrossRefGoogle ScholarPubMed
Ferrero, S et al. (2010) Loss of sympathetic nerve fibers in intestinal endometriosis. Fertility and Sterility 94, 2817–2819.CrossRefGoogle ScholarPubMed
Laschke, MW and Menger, MD (2018) Basic mechanisms of vascularization in endometriosis and their clinical implications. Human Reproduction Update 24, 207–224.CrossRefGoogle ScholarPubMed
Bouquet de Joliniere, J et al. (2021) Antiangiogenic therapy as a new strategy in the treatment of endometriosis? The first case report. Frontiers in Surgery 8, 791686.CrossRefGoogle ScholarPubMed
Apte, RS, Chen, DS and Ferrara, N (2019) VEGF in signaling and disease: beyond discovery and development. Cell 176, 1248–1264.CrossRefGoogle ScholarPubMed
Zhang, F et al. (2018) Expression of MMIF, HIF-1α and VEGF in serum and endometrial tissues of patients with endometriosis. Current Medical Science 38, 499–504.CrossRefGoogle ScholarPubMed
Hsiao, KY et al. (2015) Pathological functions of hypoxia in endometriosis. Frontiers in Bioscience 7, 352–366.CrossRefGoogle ScholarPubMed
Young, VJ et al. (2017) The role of TGF-β in the pathophysiology of peritoneal endometriosis. Human Reproduction Update 23, 548–559.CrossRefGoogle ScholarPubMed
Rashidi, BH et al. (2019) Association of vascular endothelial growth factor (VEGF) gene polymorphisms and expression with the risk of endometriosis: a case-control study. Molecular Biology Reports 46, 3445–3450.CrossRefGoogle ScholarPubMed
Zhou, J et al. (2020) Peritoneal fluid cytokines reveal new insights of endometriosis subphenotypes. International Journal of Molecular Sciences 21, 3515.CrossRefGoogle ScholarPubMed
Perricos, A et al. (2020) Does the use of the ‘Proseek(®) multiplex oncology I panel’ on peritoneal fluid allow a better insight in the pathophysiology of endometriosis, and in particular deep-infiltrating endometriosis?. Journal of Clinical Medicine 9, 2009.CrossRefGoogle Scholar
Fahey, E and Doyle, SL (2019) IL-1 family cytokine regulation of vascular permeability and angiogenesis. Frontiers in Immunology 10, 1426.CrossRefGoogle ScholarPubMed
Raimondo, D et al. (2020) Rectosigmoid endometriosis vascular patterns at intraoperative indocyanine green angiography and their correlation with clinicopathological data. Surgical Innovation 27, 474–480.CrossRefGoogle ScholarPubMed
Turco, LC et al. (2021) Near-infrared imaging with indocyanine green for the treatment of endometriosis: results from the Gre-endo trial. Frontiers in Oncology 11, 737938.CrossRefGoogle ScholarPubMed
Cohen, SP, Vase, L and Hooten, WM (2021) Chronic pain: an update on burden, best practices, and new advances. Lancet 397, 2082–2097.CrossRefGoogle ScholarPubMed
Chang, CT, Jiang, BY and Chen, CC (2019) Ion channels involved in substance P-mediated nociception and antinociception. International Journal of Molecular Sciences 20, 1596.CrossRefGoogle ScholarPubMed
Lin, FY et al. (2021) The clinical application of pulsed radiofrequency induces inflammatory pain via MAPKs activation: a novel hint for pulsed radiofrequency treatment. International Journal of Molecular Sciences 22, 11865.CrossRefGoogle ScholarPubMed
Campbell, JN and Meyer, RA (2006) Mechanisms of neuropathic pain. Neuron 52, 77–92.CrossRefGoogle ScholarPubMed
Coxon, L, Wiech, K and Vincent, K (2021) Is there a neuropathic-like component to endometriosis-associated pain? Results from a large cohort questionnaire study. Frontiers in Pain Research 2, 743812.CrossRefGoogle Scholar
Levine, JD, Fields, HL and Basbaum, AI (1993) Peptides and the primary afferent nociceptor. Journal of Neuroscience 13, 2273–2286.CrossRefGoogle ScholarPubMed
Tracey, I and Dickenson, A (2012) SnapShot: pain perception. Cell 148, 1308–1308, e2.CrossRefGoogle ScholarPubMed
Sadeghi, M et al. (2018) Contribution of membrane receptor signalling to chronic visceral pain. International Journal of Biochemistry & Cell Biology 98, 10–23.CrossRefGoogle ScholarPubMed
Nanda, A et al. (2020) Cytokines, angiogenesis, and extracellular matrix degradation are augmented by oxidative stress in endometriosis. Annals of Laboratory Medicine 40, 390–397.CrossRefGoogle ScholarPubMed
Gueuvoghlanian-Silva, BY et al. (2018) Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. Journal of Reproductive Immunology 126, 32–38.CrossRefGoogle ScholarPubMed
Soni, UK et al. (2019) A high level of TGF-β1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness. Biology of Reproduction 100, 917–938.CrossRefGoogle Scholar
Zhang, J et al. (2017) TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model. Experimental and Molecular Medicine 49, e379.CrossRefGoogle ScholarPubMed
Yu, J et al. (2018) IL-1β stimulates brain-derived neurotrophic factor production in eutopic endometriosis stromal cell cultures: a model for cytokine regulation of neuroangiogenesis. American Journal of Pathology 188, 2281–2292.CrossRefGoogle Scholar
Ma, W, Li, L and Xing, S (2019) PGE2/EP4 receptor and TRPV1 channel are involved in repeated restraint stress-induced prolongation of sensitization pain evoked by subsequent PGE2 challenge. Brain Research 1721, 146335.CrossRefGoogle ScholarPubMed
Cho, S et al. (2010) Expression of cyclooxygenase-2 in eutopic endometrium and ovarian endometriotic tissue in women with severe endometriosis. Gynecologic and Obstetric Investigation 69, 93–100.CrossRefGoogle ScholarPubMed
Mulet, M et al. (2017) Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in down syndrome. Folia Neuropathologica 55, 154–160.CrossRefGoogle ScholarPubMed
Scutiero, G et al. (2017) Oxidative stress and endometriosis: a systematic review of the literature. Oxidative Medicine and Cellular Longevity 2017, 7265238.CrossRefGoogle ScholarPubMed
Santulli, P et al. (2015) Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased. Human Reproduction 30, 49–60.CrossRefGoogle ScholarPubMed
Bulun, SE (2009) Endometriosis. New England Journal of Medicine 360, 268–279.CrossRefGoogle ScholarPubMed
Ma, J et al. (2021) Single-cell transcriptomic analysis of endometriosis provides insights into fibroblast fates and immune cell heterogeneity. Cell & Bioscience 11, 125.CrossRefGoogle ScholarPubMed
Hey-Cunningham, AJ et al. (2021) Comprehensive analysis utilizing flow cytometry and immunohistochemistry reveals inflammatory changes in local endometrial and systemic dendritic cell populations in endometriosis. Human Reproduction 36, 415–428.CrossRefGoogle ScholarPubMed
Wu, J et al. (2017) Macrophage and nerve interaction in endometriosis. Journal of Neuroinflammation 14, 53.CrossRefGoogle ScholarPubMed
Malet, M and Brumovsky, PR (2015) VGLUTs and glutamate synthesis-focus on DRG neurons and pain. Biomolecules 5, 3416–3437.CrossRefGoogle ScholarPubMed
Noh, ASM and Ismail, CAN (2020) A review on chronic pain in rheumatoid arthritis: a focus on activation of NR2B subunit of N-methyl-d-aspartate receptors. The Malaysian Journal of Medical Sciences 27, 6–21.Google ScholarPubMed
Forster, R et al. (2019) Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. FASEB Journal 33, 11210–11222.CrossRefGoogle ScholarPubMed
Aich, A, Afrin, LB and Gupta, K (2015) Mast cell-mediated mechanisms of nociception. International Journal of Molecular Sciences 16, 29069–29092.CrossRefGoogle ScholarPubMed
Borelli, V et al. (2019) Mast cells in peritoneal fluid from women with endometriosis and their possible role in modulating sperm function. Frontiers in Physiology 10, 1543.CrossRefGoogle ScholarPubMed
Genovese, T et al. (2022) Molecular and biochemical mechanism of cannabidiol in the management of the inflammatory and oxidative processes associated with endometriosis. International Journal of Molecular Sciences 23, 5427.CrossRefGoogle ScholarPubMed
Sikora, J et al. (2018) The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis. Archives of Gynecology and Obstetrics 297, 1495–1501.CrossRefGoogle ScholarPubMed
Agostinis, C et al. (2020) Immunological basis of the endometriosis: the complement system as a potential therapeutic target. Frontiers in Immunology 11, 599117.CrossRefGoogle ScholarPubMed
Agostinis, C et al. (2020) Complement Component 3 expressed by the endometrial ectopic tissue is involved in the endometriotic lesion formation through mast cell activation. bioRxiv, 2020.11.19.389536.Google Scholar
Grammatis, AL, Georgiou, EX and Becker, CM (2021) Pentoxifylline for the treatment of endometriosis-associated pain and infertility. The Cochrane Database of Systematic Reviews 8, Cd007677.Google ScholarPubMed
Gołąbek, A, Kowalska, K and Olejnik, A (2021) Polyphenols as a diet therapy concept for endometriosis – current opinion and future perspectives. Nutrients 13, 1347.CrossRefGoogle ScholarPubMed
Sun, LH et al. (2019) Estrogen modulation of visceral pain. Journal of Zhejiang University. Science B 20, 628–636.CrossRefGoogle ScholarPubMed
Hu, Z, Mamillapalli, R and Taylor, HS (2019) Increased circulating miR-370-3p regulates steroidogenic factor 1 in endometriosis. American Journal of Physiology. Endocrinology and Metabolism 316, E373–Ee82.CrossRefGoogle ScholarPubMed
Gonçalves, RM et al. (2021) COX-2 promotes mammary adipose tissue inflammation, local estrogen biosynthesis, and carcinogenesis in high-sugar/fat diet treated mice. Cancer Letters 502, 44–57.CrossRefGoogle ScholarPubMed
Ferrari, LF, Araldi, D and Levine, JD (2017) Regulation of expression of hyperalgesic priming by estrogen receptor α in the rat. The Journal of Pain 18, 574–582.CrossRefGoogle ScholarPubMed
Latini, C et al. (2008) Remodeling of uterine innervation. Cell and Tissue Research 334, 1–6.CrossRefGoogle ScholarPubMed
Dzieran, J et al. (2018) MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling. Proceedings of the National Academy of Sciences of the USA 115, E1229–E1e38.CrossRefGoogle ScholarPubMed
Greaves, E et al. (2014) Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3. Endocrinology 155, 4015–4026.CrossRefGoogle ScholarPubMed
Cao, DY et al. (2012) Estrogen receptor β activation is antinociceptive in a model of visceral pain in the rat. The Journal of Pain 13, 685–694.CrossRefGoogle Scholar
Zhang, W et al. (2020) Estrogen modulation of pain perception with a novel 17β-estradiol pretreatment regime in ovariectomized rats. Biology of Sex Differences 11, 2.CrossRefGoogle ScholarPubMed
Arosh, JA, Lee, J and Banu, SK (2022) Effects of dual inhibition of AKT and ERK1/2 pathways on endometrial pro-inflammatory, hormonal, and epigenetic microenvironment in endometriosis. Molecular and Cellular Endocrinology 539, 111446.CrossRefGoogle ScholarPubMed
Ortíz-Rentería, M et al. (2018) TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain. Proceedings of the National Academy of Sciences of the USA 115, E1657–E1e66.CrossRefGoogle ScholarPubMed
van Aken, M et al. (2018) Hair cortisol and the relationship with chronic pain and quality of life in endometriosis patients. Psychoneuroendocrinology 89, 216–222.CrossRefGoogle ScholarPubMed
Ortiz, R et al. (2020) Hypothalamic–pituitary–adrenal axis responses in women with endometriosis-related chronic pelvic pain. Reproductive Sciences 27, 1839–1847.CrossRefGoogle ScholarPubMed
van den Beukel, BA et al. (2017) Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis. Human Reproduction Update 23, 276–288.Google ScholarPubMed
Anaf, V et al. (2000) Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Human Reproduction 15, 1744–1750.CrossRefGoogle ScholarPubMed
Kalkan, Ü and Daniilidis, A (2019) Laparoscopic diagnosis and treatment of obturator nerve entrapment because of a deep infiltrating endometriotic nodule: a case report. Journal of Minimally Invasive Gynecology 26, 766–769.CrossRefGoogle ScholarPubMed
Kale, A et al. (2022) Comparison of isolated sciatic nerve and sacral nerve root endometriosis: a review of the literature. Journal of Minimally Invasive Gynecology 29, 943–951.CrossRefGoogle ScholarPubMed
Liu, Z et al. (2018) Fractalkine/CX3CR1 contributes to endometriosis-induced neuropathic pain and mechanical hypersensitivity in rats. Frontiers in Cellular Neuroscience 12, 495.CrossRefGoogle ScholarPubMed
Kamboj, AK, Hoversten, P and Oxentenko, AS (2019) Chronic abdominal wall pain: a common yet overlooked etiology of chronic abdominal pain. Mayo Clinic Proceedings 94, 139–144.CrossRefGoogle ScholarPubMed
Farag, S et al. (2018) Management, prevention, and sequelae of adhesions in women undergoing laparoscopic gynecologic surgery: a systematic review. Journal of Minimally Invasive Gynecology 25, 1194–1216.CrossRefGoogle ScholarPubMed
Grundy, L, Erickson, A and Brierley, SM (2019) Visceral pain. Annual Review of Physiology 81, 261–284.CrossRefGoogle ScholarPubMed
Basbaum, AI et al. (2009) Cellular and molecular mechanisms of pain. Cell 139, 267–284.CrossRefGoogle ScholarPubMed
Hayashi, S et al. (2020) Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice. Redox Biology 37, 101726.CrossRefGoogle ScholarPubMed
Maatuf, Y, Geron, M and Priel, A (2019) The role of toxins in the pursuit for novel analgesics. Toxins (Basel) 11, 131.CrossRefGoogle ScholarPubMed
Finnerup, NB, Kuner, R and Jensen, TS (2021) Neuropathic pain: from mechanisms to treatment. Physiological Reviews 101, 259–301.CrossRefGoogle ScholarPubMed
Hoffman, D (2015) Central and peripheral pain generators in women with chronic pelvic pain: patient centered assessment and treatment. Current Rheumatology Reviews 11, 146–166.CrossRefGoogle ScholarPubMed
Phan, VT et al. (2021) Widespread myofascial dysfunction and sensitisation in women with endometriosis-associated chronic pelvic pain: a cross-sectional study. European Journal of Pain 25, 831–840.CrossRefGoogle ScholarPubMed
Gruber, TM and Mechsner, S (2021) Pathogenesis of endometriosis: the origin of pain and subfertility. Cells 10, 1381.CrossRefGoogle ScholarPubMed
Lopes, DM, Denk, F and McMahon, SB (2017) The molecular fingerprint of dorsal root and trigeminal ganglion neurons. Frontiers in Molecular Neuroscience 10, 304.CrossRefGoogle ScholarPubMed
Hucho, T and Levine, JD (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55, 365–376.CrossRefGoogle Scholar
Abbas, MA (2020) Modulation of TRPV1 channel function by natural products in the treatment of pain. Chemico-Biological Interactions 330, 109178.CrossRefGoogle ScholarPubMed
Bohonyi, 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. Molecular Pain 13, 1744806917705564.CrossRefGoogle ScholarPubMed
Fattori, V et al. (2020) Nonsurgical mouse model of endometriosis-associated pain that responds to clinically active drugs. Pain 161, 1321–1331.CrossRefGoogle ScholarPubMed
McAllister, SL et al. (2021) Aberrant reactive aldehyde detoxification by aldehyde dehydrogenase-2 influences endometriosis development and pain-associated behaviors. Pain 162, 71–83.CrossRefGoogle ScholarPubMed
Trapero, C et al. (2019) Impaired expression of ectonucleotidases in ectopic and eutopic endometrial tissue is in favor of ATP accumulation in the tissue microenvironment in endometriosis. International Journal of Molecular Sciences 20, 5532.CrossRefGoogle ScholarPubMed
Orr, MB and Gensel, JC (2018) Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics 15, 541–553.CrossRefGoogle ScholarPubMed
Kwon, SG et al. (2014) Blockade of peripheral P2Y1 receptors prevents the induction of thermal hyperalgesia via modulation of TRPV1 expression in carrageenan-induced inflammatory pain rats: involvement of p38 MAPK phosphorylation in DRGs. Neuropharmacology 79, 368–379.CrossRefGoogle ScholarPubMed
Trapero, C and Martín-Satué, M (2020) Purinergic signaling in endometriosis-associated pain. International Journal of Molecular Sciences 21, 8512.CrossRefGoogle ScholarPubMed
Ding, S et al. (2020) Activation of ATF3/AP-1 signaling pathway is required for P2X3-induced endometriosis pain. Human Reproduction 35, 1130–1144.CrossRefGoogle ScholarPubMed
Xiang, X et al. (2019) Electroacupuncture stimulation alleviates CFA-induced inflammatory pain via suppressing P2X3 expression. International Journal of Molecular Sciences 20, 3248.CrossRefGoogle ScholarPubMed
Greaves, E et al. (2014) Elevated peritoneal expression and estrogen regulation of nociceptive ion channels in endometriosis. Journal of Clinical Endocrinology and Metabolism 99, E1738–E1743.CrossRefGoogle ScholarPubMed
Greaves, E et al. (2017) EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Scientific Reports 7, 44169.CrossRefGoogle Scholar
Zhou, YM et al. (2019) Enhancement of acid-sensing ion channel activity by prostaglandin E2 in rat dorsal root ganglion neurons. Brain Research 1724, 146442.CrossRefGoogle ScholarPubMed
Riemma, G et al. (2020) Ion channels in the pathogenesis of endometriosis: a cutting-edge point of view. International Journal of Molecular Sciences 21, 1114.CrossRefGoogle ScholarPubMed
Maulitz, L et al. (2022) Endometriosis, psychiatric comorbidities and neuroimaging: estimating the odds of an endometriosis brain. Frontiers in Neuroendocrinology 65, 100988.CrossRefGoogle ScholarPubMed
Yang, S and Chang, MC (2019) Chronic pain: structural and functional changes in brain structures and associated negative affective states. International Journal of Molecular Sciences 20, 3130.CrossRefGoogle ScholarPubMed
Tu, CH et al. (2013) Menstrual pain is associated with rapid structural alterations in the brain. Pain 154, 1718–1724.CrossRefGoogle Scholar
Vincent, K et al. (2011) Dysmenorrhoea is associated with central changes in otherwise healthy women. Pain 152, 1966–1975.CrossRefGoogle ScholarPubMed
As-Sanie, S et al. (2012) Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain 153, 1006–1014.CrossRefGoogle ScholarPubMed
Matsuo, Y et al. (2017) Attenuation of cortical activity triggering descending pain inhibition in chronic low back pain patients: a functional magnetic resonance imaging study. Journal of Anesthesia 31, 523–530.CrossRefGoogle ScholarPubMed
Kang, D et al. (2019) What does the grey matter decrease in the medial prefrontal cortex reflect in people with chronic pain? European Journal of Pain 23, 203–219.CrossRefGoogle ScholarPubMed
Ferdek, MA et al. (2019) Effective connectivity of beta oscillations in endometriosis-related chronic pain during rest and pain-related mental imagery. The Journal of Pain 20, 1446–1458.CrossRefGoogle ScholarPubMed
As-Sanie, S et al. (2016) Functional connectivity is associated with altered brain chemistry in women with endometriosis-associated chronic pelvic pain. The Journal of Pain 17, 1–13.CrossRefGoogle ScholarPubMed
Ong, WY, Stohler, CS and Herr, DR (2019) Role of the prefrontal cortex in pain processing. Molecular Neurobiology 56, 1137–1166.CrossRefGoogle ScholarPubMed
Duncan, NW et al. (2013) Glutamate concentration in the medial prefrontal cortex predicts resting-state cortical-subcortical functional connectivity in humans. PLoS ONE 8, e60312.CrossRefGoogle ScholarPubMed
Huang, J et al. (2019) A neuronal circuit for activating descending modulation of neuropathic pain. Nature Neuroscience 22, 1659–1668.CrossRefGoogle ScholarPubMed
Cortés-Montero, E et al. (2020) Calmodulin supports TRPA1 channel association with opioid receptors and glutamate NMDA receptors in the nervous tissue. International Journal of Molecular Sciences 22, 229.CrossRefGoogle ScholarPubMed
Torres-Reverón, A et al. (2016) Endometriosis is associated with a shift in MU opioid and NMDA receptor expression in the brain periaqueductal gray. Reproductive Sciences 23, 1158–1167.CrossRefGoogle ScholarPubMed
Brawn, J et al. (2014) Central changes associated with chronic pelvic pain and endometriosis. Human Reproduction Update 20, 737–747.CrossRefGoogle ScholarPubMed
Yano, M et al. (2019) Pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis. Human Reproduction 34, 469–478.CrossRefGoogle ScholarPubMed
Colvin, LA, Bull, F and Hales, TG (2019) Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet 393, 1558–1568.CrossRefGoogle Scholar
Buehlmann, D et al. (2019) Prospective administration of anti-nerve growth factor treatment effectively suppresses functional connectivity alterations after cancer-induced bone pain in mice. Pain 160, 151–159.CrossRefGoogle ScholarPubMed
Umbrain, V et al. (2008) Intrathecal lidocaine elevates prostaglandin E2 levels in cerebrospinal fluid: a microdialysis study in freely moving rats. British Journal of Anaesthesia 101, 716–722.CrossRefGoogle ScholarPubMed
Zheng, P et al. (2019) Evaluation of the brain functional activities in rats various location-endometriosis pain model. Annals of Translational Medicine 7, 767.CrossRefGoogle ScholarPubMed
Kuhn, A (2019) Chronic pelvic pain. Therapeutische Umschau 73, 573–575.Google ScholarPubMed
Wimmer, GE and Büchel, C (2021) Reactivation of single-episode pain patterns in the hippocampus and decision making. Journal of Neuroscience 41, 7894–7908.CrossRefGoogle ScholarPubMed
Li, T et al. (2018) Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biology of Reproduction 99, 349–359.CrossRefGoogle ScholarPubMed
Beissner, F et al. (2018) Psychotherapy with somatosensory stimulation for endometriosis-associated pain: the role of the anterior hippocampus. Biological Psychiatry 84, 734–742.CrossRefGoogle ScholarPubMed
Padda, J et al. (2021) Depression and its effect on the menstrual cycle. Cureus 13, e16532.Google ScholarPubMed
Hansen, KB et al. (2017) NMDA receptors in the central nervous system. Methods in Molecular Biology 1677, 1–80.CrossRefGoogle ScholarPubMed
Zheng, P et al. (2020) Central sensitization-related changes in brain function activity in a rat endometriosis-associated pain model. Journal of Pain Research 13, 95–107.CrossRefGoogle Scholar
Xu, B et al. (2000) The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB. Journal of Neuroscience 20, 6888–6897.CrossRefGoogle ScholarPubMed
Cordaro, M et al. (2021) Hidrox(®) and endometriosis: biochemical evaluation of oxidative stress and pain. Antioxidants (Basel) 10, 720.CrossRefGoogle ScholarPubMed
Rostami, J et al. (2021) Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates. Journal of Neuroinflammation 18, 124.CrossRefGoogle ScholarPubMed
Flores-Bonilla, A et al. (2019) Astrocyte activation is increased in a rat endometriosis model. The FASEB Journal 33, lb619–lb619.CrossRefGoogle Scholar