scholarly journals Elevated Peritoneal Expression and Estrogen Regulation of Nociceptive Ion Channels in Endometriosis

2014 ◽  
Vol 99 (9) ◽  
pp. E1738-E1743 ◽  
Author(s):  
Erin Greaves ◽  
Kelsey Grieve ◽  
Andrew W. Horne ◽  
Philippa T. K. Saunders
Keyword(s):  
Ion Channels ◽  
Sensory Neurons ◽  
Pelvic Pain ◽  
Human Tissue ◽  
Embryonic Stem ◽  
Estrogen Regulation ◽  
Tissue Samples ◽  
Ovarian Suppression ◽  
17Β Estradiol ◽  
Nociceptive Ion Channels

Context: Ovarian suppression is a common treatment for endometriosis-associated pelvic pain. Its exact mechanism of action is poorly understood, although it is assumed to reflect reduced production/action of estrogens. Objective: The objective of the study was to measure the expression of mRNAs encoded by nociceptive genes in the peritoneum of women with chronic pelvic pain (CPP) with or without endometriosis and to investigate whether estrogens alter nociceptive gene expression in human sensory neurons. Design: The study was performed using human tissue analysis and cell culture. Setting: The study was conducted at a university research institute. Patients: Peritoneal biopsies were obtained from women with CPP and endometriosis (n = 12), CPP and no endometriosis (n = 10), and no pain or endometriosis (n = 5). Endometriosis lesions were obtained from women with endometriosis (n = 18). Main Outcome Measures: mRNAs encoding ion channels (P2RX3, SCN9A, SCN11A, TRPA1, TRPV1) and the neurotransmitter TAC1 were measured in human tissue samples and in human embryonic stem cell-derived sensory neurons treated with estrogens. Results: TRPV1, TRPA1, and SCN11A mRNAs were significantly higher in the peritoneum from women with endometriosis (P < .001, P < .01). TRPV1, SCN9A, and TAC1 were elevated in endometriosis lesions (P < .05). P2RX3 mRNA was increased in the peritoneum of women with CPP, with and without endometriosis (P < .05). Incubation of sensory neurons with 17β-estradiol increased TRPV1 mRNA (P < .01). The estrogen receptor-β-selective agonist 2,3-bis(4-hydroxy-phenyl)-propionitrile increased concentrations of TRPV1, P2RX3, SCN9A, and TAC1 mRNAs. Conclusions: Estrogen-dependent expression of TRPV1 in sensory neurons may explain why ovarian suppression can reduce endometriosis-associated pain. Strategies directly targeting ion channels may offer an alternative option for the management of CPP.

Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 4015-4026 ◽  
Author(s):  
Erin Greaves ◽  
Frances Collins ◽  
Arantza Esnal-Zufiaurre ◽  
Sevasti Giakoumelou ◽  
Andrew W. Horne ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Network Formation ◽  
Uterine Cavity ◽  
Axonal Guidance ◽  
Estrogen Regulation ◽  
Tissue Samples ◽  
Peritoneal Endometriosis ◽  
Peritoneal Wall ◽  
17Β Estradiol ◽  
Dorsal Root Ganglia Neurons

Abstract Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17β-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ERα agonist, 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ERβ agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17β-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.

Analysis of ∼700 Human Tissue Samples Identifies microRNAs That Are Associated with, Predictive of, and Necessary for Insulin Gene Transcription

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2160-P
Author(s):  
ANAND HARDIKAR ◽  
WILSON WONG ◽  
MUGDHA JOGLEKAR ◽  
LOUISE T. DALGAARD ◽  
ALICIA JENKINS ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Human Tissue ◽  
Insulin Gene ◽  
Tissue Samples ◽  
Insulin Gene Transcription

scholarly journals Biophysics and Modeling of Mechanotransduction in Neurons: A Review

Mathematics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 323
Author(s):  
Martina Nicoletti ◽  
Letizia Chiodo ◽  
Alessandro Loppini
Keyword(s):  
Ion Channels ◽  
Cell Membrane ◽  
Sensory Neurons ◽  
Neuronal Cell ◽  
Molecular Processes ◽  
Biological Mechanisms ◽  
Mechanosensitive Ion Channels ◽  
Complex Interactions ◽  
Different Types ◽  
Intracellular Organelles

Mechanosensing is a key feature through which organisms can receive inputs from the environment and convert them into specific functional and behavioral outputs. Mechanosensation occurs in many cells and tissues, regulating a plethora of molecular processes based on the distribution of forces and stresses both at the cell membrane and at the intracellular organelles levels, through complex interactions between cells’ microstructures, cytoskeleton, and extracellular matrix. Although several primary and secondary mechanisms have been shown to contribute to mechanosensation, a fundamental pathway in simple organisms and mammals involves the presence of specialized sensory neurons and the presence of different types of mechanosensitive ion channels on the neuronal cell membrane. In this contribution, we present a review of the main ion channels which have been proven to be significantly involved in mechanotransduction in neurons. Further, we discuss recent studies focused on the biological mechanisms and modeling of mechanosensitive ion channels’ gating, and on mechanotransduction modeling at different scales and levels of details.

scholarly journals Human tissue samples more difficult to obtain for academics

2002 ◽  
Vol 8 (6) ◽  
pp. 543-543
Author(s):  
David Dickson
Keyword(s):  
Human Tissue ◽  
Tissue Samples

scholarly journals Acid-sensing ion channels in sensory signaling

2020 ◽  
Vol 318 (3) ◽  
pp. F531-F543 ◽  
Author(s):  
Marcelo D. Carattino ◽  
Nicolas Montalbetti
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Genetically Modified ◽  
Physiological Processes ◽  
Acid Sensing Ion Channels ◽  
Genetically Modified Mice ◽  
Sensory Processes

Acid-sensing ion channels (ASICs) are cation-permeable channels that in the periphery are primarily expressed in sensory neurons that innervate tissues and organs. Soon after the cloning of the ASIC subunits, almost 20 yr ago, investigators began to use genetically modified mice to assess the role of these channels in physiological processes. These studies provide critical insights about the participation of ASICs in sensory processes, including mechanotransduction, chemoreception, and nociception. Here, we provide an extensive assessment of these findings and discuss the current gaps in knowledge with regard to the functions of ASICs in the peripheral nervous system.

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