Altered GABAA receptor function in women with endometriosis: a possible pain‐related mechanism
Introduction The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our...
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| Vydané v: | Acta obstetricia et gynecologica Scandinavica Ročník 102; číslo 10; s. 1316 - 1322 |
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| Hlavní autori: | , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Reykjavik
John Wiley & Sons, Inc
01.10.2023
John Wiley and Sons Inc Wiley |
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| ISSN: | 0001-6349, 1600-0412, 1600-0412 |
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| Abstract | Introduction
The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.
Material and methods
15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom‐free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.
Results
Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.
Conclusions
Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist.
Women with endometriosis show a significantly decreased GABAA receptor‐mediated inhibition compared with healthy controls, indicating changes in the central nervous system that could explain why treatment targeted at the nociceptive component of the pain sometimes fails in these women. |
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| AbstractList | The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.INTRODUCTIONThe mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA ) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.MATERIAL AND METHODS15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18-40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.RESULTSCompared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist.CONCLUSIONSWomen with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. Abstract Introduction The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women. Material and methods 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom‐free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection. Results Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels. Conclusions Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. IntroductionThe mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.Material and methods15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom‐free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.ResultsCompared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.ConclusionsWomen with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relationship between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women. Material and methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection. Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels. Conclusions: Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. Women with endometriosis show a significantly decreased GABAA receptor‐mediated inhibition compared with healthy controls, indicating changes in the central nervous system that could explain why treatment targeted at the nociceptive component of the pain sometimes fails in these women. Introduction The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relation between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women. Material and methods 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom‐free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection. Results Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels. Conclusions Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist. Women with endometriosis show a significantly decreased GABAA receptor‐mediated inhibition compared with healthy controls, indicating changes in the central nervous system that could explain why treatment targeted at the nociceptive component of the pain sometimes fails in these women. |
| Author | Turkmen, Sahruh Bäckström, Torbjörn Möller, Anna Bixo, Marie Sandström, Anton |
| AuthorAffiliation | 4 Department of Clinical Science and Education Karolinska Institutet Stockholm Sweden 3 Department of Obstetrics and Gynecology Stockholm South General Hospital Stockholm Sweden 2 Department of Obstetrics and Gynecology Sundsvall County Hospital Sundsvall Sweden 1 Department of Clinical Sciences, Obstetrics and Gynecology Umea University Umea Sweden |
| AuthorAffiliation_xml | – name: 4 Department of Clinical Science and Education Karolinska Institutet Stockholm Sweden – name: 2 Department of Obstetrics and Gynecology Sundsvall County Hospital Sundsvall Sweden – name: 3 Department of Obstetrics and Gynecology Stockholm South General Hospital Stockholm Sweden – name: 1 Department of Clinical Sciences, Obstetrics and Gynecology Umea University Umea Sweden |
| Author_xml | – sequence: 1 givenname: Anton orcidid: 0000-0002-3037-4199 surname: Sandström fullname: Sandström, Anton organization: Sundsvall County Hospital – sequence: 2 givenname: Marie orcidid: 0000-0002-4988-1967 surname: Bixo fullname: Bixo, Marie organization: Umea University – sequence: 3 givenname: Torbjörn orcidid: 0000-0002-0907-3535 surname: Bäckström fullname: Bäckström, Torbjörn organization: Umea University – sequence: 4 givenname: Anna orcidid: 0000-0002-4097-6169 surname: Möller fullname: Möller, Anna organization: Karolinska Institutet – sequence: 5 givenname: Sahruh orcidid: 0000-0002-4367-4959 surname: Turkmen fullname: Turkmen, Sahruh email: sahruh.turkmen@umu.se organization: Sundsvall County Hospital |
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| Copyright | 2023 The Authors. published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). 2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). |
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The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA)... IntroductionThe mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid (GABA) type... The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA )... Women with endometriosis show a significantly decreased GABAA receptor‐mediated inhibition compared with healthy controls, indicating changes in the central... Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA)... Abstract Introduction The mechanism underlying endometriosis‐related pain remains poorly understood. Previous studies have indicated that γ‐aminobutyric acid... |
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| SubjectTerms | allopregnanolone central sensitisation Endometriosis GABA Neurotransmitters Original Pain Pathophysiology Progesterone Steroids |
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| Title | Altered GABAA receptor function in women with endometriosis: a possible pain‐related mechanism |
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