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

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.

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

“…In this investigation, we identified enriched genes in GO terms and signaling pathways that might be utilized as diagnostic and/or therapeutic targets in endometriosis. Signaling pathways include extracellular matrix organization [101], nervous system development [102], signal transduction [103], hemostasis [104], muscle contraction [105], signaling by retinoic acid [106] and diseases of glycosylation [107] were responsible for advancement of endometriosis. Altered expression of L1CAM [108], HSD17B2 [109], VCAM1 [110], SOX6 [111], FGF10 [112], MMP12 [113], CCR1 [114], PROK1 [115], PRL (prolactin) [116], TIMP3 [117], ADAMTS9 [118], NDNF (neuron derived neurotrophic factor) [119], LHCGR (luteinizing hormone/choriogonadotropin receptor) [120], PDGFB (platelet derived growth factor subunit B) [121], LDLR (low density lipoprotein receptor) [122], CD4 [123], FOXL2 [124], TRPA1 [125], ADRB2 [126], PLAU (plasminogen activator, urokinase) [127], EPCAM (epithelial cell adhesion molecule) [128], UCN2 [129], CYP1A1 [130], NTN1 [131], IL15 [132], BMP2 [133], APOE (apolipoprotein E) [134], CASP1 [135], ABCG2 [136], ACE (angiotensin I converting enzyme) [137], PGR (progesterone receptor) [138], ALPP (alkaline phosphatase, placental) [139], LPAR4 [140], ATRNL1 [141], HLA-C [142], MMP3 [143], PDLIM3 [144], NFASC (neurofascin) [145], IL33 [146], NGF (nerve growth factor) [147], COMP (cartilage oligomeric matrix protein) [148], FST (follistatin) [149], EFEMP1 [150], GATA6 [151], TCF21 [152], PTGS2 [153], HOXC8 [154], AKR1C3 [155], BDNF (brain derived neurotrophic factor) [119], EPHA3 [156], INHBA (inhibin subunit beta A) [157], RAP1GAP [158], TLR3 [159], NOX4 [160], TGFBI (transforming growth factor beta induced) [161], IGF2B...…”