Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Jaesung, Chung, Seohyun, Hwang, Minkyu, Kwon, Yeongkag, Han, Seung Hyun, Lee, Sung Joong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1784904031337971712
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
work_keys_str_mv AT leejaesung estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization
AT chungseohyun estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization
AT hwangminkyu estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization
AT kwonyeongkag estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization
AT hanseunghyun estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization
AT leesungjoong estrogenmediatesthesexualdimorphismofgt1binducedcentralpainsensitization