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Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization
We have previously reported that the intrathecal (i.t.) administration of GT1b, a ganglioside, induces spinal cord microglia activation and central pain sensitization as an endogenous agonist of Toll-like receptor 2 on microglia. In this study, we investigated the sexual dimorphism of GT1b-induced c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001026/ https://www.ncbi.nlm.nih.gov/pubmed/36899944 http://dx.doi.org/10.3390/cells12050808 |
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author | Lee, Jaesung Chung, Seohyun Hwang, Minkyu Kwon, Yeongkag Han, Seung Hyun Lee, Sung Joong |
author_facet | Lee, Jaesung Chung, Seohyun Hwang, Minkyu Kwon, Yeongkag Han, Seung Hyun Lee, Sung Joong |
author_sort | Lee, Jaesung |
collection | PubMed |
description | We have previously reported that the intrathecal (i.t.) administration of GT1b, a ganglioside, induces spinal cord microglia activation and central pain sensitization as an endogenous agonist of Toll-like receptor 2 on microglia. In this study, we investigated the sexual dimorphism of GT1b-induced central pain sensitization and the underlying mechanisms. GT1b administration induced central pain sensitization only in male but not in female mice. Spinal tissue transcriptomic comparison between male and female mice after GT1b injection suggested the putative involvement of estrogen (E2)-mediated signaling in the sexual dimorphism of GT1b-induced pain sensitization. Upon ovariectomy-reducing systemic E2, female mice became susceptible to GT1b-induced central pain sensitization, which was completely reversed by systemic E2 supplementation. Meanwhile, orchiectomy of male mice did not affect pain sensitization. As an underlying mechanism, we present evidence that E2 inhibits GT1b-induced inflammasome activation and subsequent IL-1β production. Our findings demonstrate that E2 is responsible for sexual dimorphism in GT1b-induced central pain sensitization. |
format | Online Article Text |
id | pubmed-10001026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100010262023-03-11 Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization Lee, Jaesung Chung, Seohyun Hwang, Minkyu Kwon, Yeongkag Han, Seung Hyun Lee, Sung Joong Cells Article We have previously reported that the intrathecal (i.t.) administration of GT1b, a ganglioside, induces spinal cord microglia activation and central pain sensitization as an endogenous agonist of Toll-like receptor 2 on microglia. In this study, we investigated the sexual dimorphism of GT1b-induced central pain sensitization and the underlying mechanisms. GT1b administration induced central pain sensitization only in male but not in female mice. Spinal tissue transcriptomic comparison between male and female mice after GT1b injection suggested the putative involvement of estrogen (E2)-mediated signaling in the sexual dimorphism of GT1b-induced pain sensitization. Upon ovariectomy-reducing systemic E2, female mice became susceptible to GT1b-induced central pain sensitization, which was completely reversed by systemic E2 supplementation. Meanwhile, orchiectomy of male mice did not affect pain sensitization. As an underlying mechanism, we present evidence that E2 inhibits GT1b-induced inflammasome activation and subsequent IL-1β production. Our findings demonstrate that E2 is responsible for sexual dimorphism in GT1b-induced central pain sensitization. MDPI 2023-03-06 /pmc/articles/PMC10001026/ /pubmed/36899944 http://dx.doi.org/10.3390/cells12050808 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Jaesung Chung, Seohyun Hwang, Minkyu Kwon, Yeongkag Han, Seung Hyun Lee, Sung Joong Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title | Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title_full | Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title_fullStr | Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title_full_unstemmed | Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title_short | Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization |
title_sort | estrogen mediates the sexual dimorphism of gt1b-induced central pain sensitization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10001026/ https://www.ncbi.nlm.nih.gov/pubmed/36899944 http://dx.doi.org/10.3390/cells12050808 |
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