Pain Mechanisms in Peritoneal Diseases Might Be Partially Regulated by Estrogen

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Peritoneal fluid estrogen concentration, total, and sensory nerve fiber density were higher in endometriosis than ovarian cancer, suggesting estrogen influences pain genesis in endometriosis.

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The study compared pain-related mechanisms in peritoneal endometriosis (pEM) versus peritoneal carcinomatosis from ovarian cancer (pOC) by analyzing peritoneal tissues and fluids from patients undergoing laparoscopy or laparotomy. Immunohistochemical staining assessed nerve fiber density and neurotrophins in peritoneal samples (18 pEM, 15 pOC, 15 controls), while fluid neurotrophin expression was measured (pEM fluids, pOC ascites, and myoma uteri fluids as controls) and neurotrophic activity was tested using a chicken sensory ganglia neurite outgrowth assay; estrogen levels were quantified in fluids and ascites by electrochemiluminescence immunoassay. The authors found higher total and sensory nerve fiber density in pEM than in pOC, detected neurotrophins in both disease settings, and showed that pEM and pOC fluids promoted sensory nerve fiber outgrowth; additionally, estrogen concentrations in pEM peritoneal fluid were significantly higher than estrogen levels in pOC ascites, and estrogen expression in pEM was notably higher than in pOC. The paper’s caveat is that it does not directly demonstrate causality in humans beyond associational evidence, and the estrogen/neurotrophin functional findings rely on ex vivo assays and comparative tissue/fluid measurements. This paper is centrally about endometriosis — focusing on estrogen-associated regulation of pain mechanisms in peritoneal endometriosis by linking higher estrogen levels to increased nerve fiber density and neurotrophin-driven neurite outgrowth.

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Abstract

To identify factors influencing the differential pain pathogenesis in peritoneal endometriosis (pEM) and peritoneal carcinomatosis in ovarian cancer (pOC), we undertook an experimental study. Tissue samples of 18 patients with pEM, 15 patients with pOC, and 15 unaffected peritoneums as controls were collected during laparoscopy or laparotomy. Immunohistochemical stainings were conducted to identify nerve fibers and neurotrophins in the tissue samples. Additionally, 23 pEM fluids, 25 pOC ascites fluids, and 20 peritoneal fluids of patients with myoma uteri as controls were collected. In these fluids, the expression of neurotrophins was evaluated. The effects of peritoneal fluids and ascites on the neurite outgrowth of chicken sensory ganglia were estimated by using a neuronal growth assay. An electrochemiluminescence immunoassay was carried out to determine the expression of estrogen in the peritoneal fluids and ascites. The total and sensory nerve fiber density was significantly higher in pEM than in pOC ( P < .001 and P < .01). All neurotrophins tested were present in tissue and fluid samples of pEM and pOC. Furthermore, the neurotrophic properties of pEM and pOC fluids were demonstrated, leading to sensory nerve fiber outgrowth. Estrogen concentration in the peritoneal fluids of pEM was significantly higher compared to ascites of pOC ( P < .001). The total and sensory nerve fiber density in the tissue samples as well as the estrogen expression in the peritoneal fluid of pEM was considerably higher than that in pOC, representing the most notable difference found in both diseases. This might explain the differential pain perception in pEM and pOC. Therefore, estrogen might be a key factor in influencing the genesis of pain in endometriosis.
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Abstract

To identify factors influencing the differential pain pathogenesis in peritoneal endometriosis (pEM) and peritoneal carcinomatosis in ovarian cancer (pOC), we undertook an experimental study. Tissue samples of 18 patients with pEM, 15 patients with pOC, and 15 unaffected peritoneums as controls were collected during laparoscopy or laparotomy. Immunohistochemical stainings were conducted to identify nerve fibers and neurotrophins in the tissue samples. Additionally, 23 pEM fluids, 25 pOC ascites fluids, and 20 peritoneal fluids of patients with myoma uteri as controls were collected. In these fluids, the expression of neurotrophins was evaluated. The effects of peritoneal fluids and ascites on the neurite outgrowth of chicken sensory ganglia were estimated by using a neuronal growth assay. An electrochemiluminescence immunoassay was carried out to determine the expression of estrogen in the peritoneal fluids and ascites. The total and sensory nerve fiber density was significantly higher in pEM than in pOC (P <.001 and P <.01). All neurotrophins tested were present in tissue and fluid samples of pEM and pOC. Furthermore, the neurotrophic properties of pEM and pOC fluids were demonstrated, leading to sensory nerve fiber outgrowth. Estrogen concentration in the peritoneal fluids of pEM was significantly higher compared to ascites of pOC (P <.001). The total and sensory nerve fiber density in the tissue samples as well as the estrogen expression in the peritoneal fluid of pEM was considerably higher than that in pOC, representing the most notable difference found in both diseases. This might explain the differential pain perception in pEM and pOC. Therefore, estrogen might be a key factor in influencing the genesis of pain in endometriosis. Similar content being viewed by others

References

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Chakrabarty A, Blacklock A, Svojanovsky S, Smith PG. Estrogen elicits dorsal root ganglion axon sprouting via a renin-angiotensin system. Endocrinology. 2008;149(7):3452–3460. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Börner, C., Scheerer, C., Buschow, R. et al. Pain Mechanisms in Peritoneal Diseases Might Be Partially Regulated by Estrogen. Reprod. Sci. 25, 424–434 (2018). https://doi.org/10.1177/1933719117715126 Published: Version of record: Issue date: DOI: https://doi.org/10.1177/1933719117715126

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endometriosis

MeSH descriptors

Carcinoma Endometriosis Estrogens Pain Peritoneal Diseases Adult Animals Ascites Ascites Ascitic Fluid Ascitic Fluid Carcinoma Endometriosis Estrogens Female Humans Middle Aged Neurites Neurites Pain

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