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THE ROLE OF ESTROGEN RECEPTORS AND NOCICEPTIVE SIGNALING PATHWAY OF PRIMARY SENSORY NEURONS
by
Tae Hoon Cho
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CHEMICAL ENGINEERING)
August 2012
Copyright 2012 Tae Hoon Cho
Object Description
| Title | The role of estrogen receptors and nociceptive signaling pathway of primary sensory neurons |
| Author | Cho, Tae Hoon |
| Author email | taecho@usc.edu;uscbioman@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Chemical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2012-04-30 |
| Date submitted | 2012-05-24 |
| Date approved | 2012-05-24 |
| Restricted until | 2012-05-24 |
| Date published | 2012-05-24 |
| Advisor (committee chair) | Wang, Pin |
| Advisor (committee member) |
Shing, Katherine Zhang, Li |
| Abstract | Clinical studies suggest the comorbidity of functional pain syndromes such as irritable bowel syndrome (IBS), chronic pelvic pain (CPP), fibromyalgia, and somatoform disorders approaches 40% to 60%. The incidence of episodic or persistent visceral pain associated with these functional disorders is two to three times higher women than in men. One of the possible explanations for this phenomenon is the estrogen modulation of pain transmission. While a central site of this modulation has been shown previously, here we proposed to study a peripheral site, the dorsal root ganglion (DRG). In DRG neurons, 17β-estradiol (E2) rapidly inhibits intracellular calcium ([Ca²⁺]i) flux induced by ATP, a putative nociceptive signal. This proposal, ""Estrogen Receptors mediate Nociceptive Signaling in Primary Sensory Neurons in Female Mice"" will test a general hypothesis that E2 acting on primary afferent nociceptors has both pro-nociceptive and anti-nociceptive effects depending on which signals converge upon DRG. First, the role of different estrogen receptors (ERs) in E2 activation of purinergic (P2X3) and vanilloid (TRPV1) receptors will be studied in wild type, estrogen receptor-α, and estrogen receptor-β knock-out mice. Second, since we hypothesize that E2 may act differently on visceral then on cutaneous nociceptors, we will compare the [Ca²⁺]i response to activation of P2X3 and TRPV1 receptors in retrogradely-labeled visceral and cutaneous DRG neurons from knock-out and wild type mice. Third, E2 may negatively modulate opioid analgesia by interfering with μ-opioid receptor (MOR). Pharmacological manipulations will be used to determine how ER activation modulates Ca2+ channel and MOR functions. Receptor binding will determine if E2 alters the number and affinity of MOR in the DRG and the site-specific regulation of MOR coupling to G-proteins. Together these experiments will define a new site(s) and mechanism of E2 modulation of nociceptive signaling. Furthermore, they will provide important information about the action of E2 on primary sensory neurons for a better understanding of sex-differences observed in the clinical presentation of functional pain-associated syndromes. Nociceptive systems implicated in the etiology of functional disorders, which often are complicated by comorbid depression will have a major impact on health-related quality of life in patients with functional pain disorders, significantly reducing therapeutic interventions. |
| Keyword | 17beta-estradiol; DRG; ATP; Capsaicin; calcium; estrogen receptor alpha; estrogen receptor beta |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | Cho, Tae Hoon |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-ChoTaeHoon-860.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | THE ROLE OF ESTROGEN RECEPTORS AND NOCICEPTIVE SIGNALING PATHWAY OF PRIMARY SENSORY NEURONS by Tae Hoon Cho A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMICAL ENGINEERING) August 2012 Copyright 2012 Tae Hoon Cho |
