Cargando…
IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice
Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052634/ https://www.ncbi.nlm.nih.gov/pubmed/36982563 http://dx.doi.org/10.3390/ijms24065479 |
_version_ | 1785015205063819264 |
---|---|
author | Fülöp, Barbara Hunyady, Ágnes Bencze, Noémi Kormos, Viktória Szentes, Nikolett Dénes, Ádám Lénárt, Nikolett Borbély, Éva Helyes, Zsuzsanna |
author_facet | Fülöp, Barbara Hunyady, Ágnes Bencze, Noémi Kormos, Viktória Szentes, Nikolett Dénes, Ádám Lénárt, Nikolett Borbély, Éva Helyes, Zsuzsanna |
author_sort | Fülöp, Barbara |
collection | PubMed |
description | Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15–20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes. |
format | Online Article Text |
id | pubmed-10052634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100526342023-03-30 IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice Fülöp, Barbara Hunyady, Ágnes Bencze, Noémi Kormos, Viktória Szentes, Nikolett Dénes, Ádám Lénárt, Nikolett Borbély, Éva Helyes, Zsuzsanna Int J Mol Sci Article Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1 (IL-1) has been described in stress and inflammatory pain but no data are available regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS) mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception, cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic protein (GFAP) integrated density, number and morphological transformation in pain-related brain regions were determined. CRS induced 15–20% mechanical hyperalgesia after 2 weeks in WT mice in both sexes, which was significantly reduced in female but not in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala, primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like behaviors, thymus and adrenal gland weight changes were detectable in all groups after 2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced hyperalgesia in female mice, without other major behavioral alterations, suggesting the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes. MDPI 2023-03-13 /pmc/articles/PMC10052634/ /pubmed/36982563 http://dx.doi.org/10.3390/ijms24065479 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 Fülöp, Barbara Hunyady, Ágnes Bencze, Noémi Kormos, Viktória Szentes, Nikolett Dénes, Ádám Lénárt, Nikolett Borbély, Éva Helyes, Zsuzsanna IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title | IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title_full | IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title_fullStr | IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title_full_unstemmed | IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title_short | IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice |
title_sort | il-1 mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052634/ https://www.ncbi.nlm.nih.gov/pubmed/36982563 http://dx.doi.org/10.3390/ijms24065479 |
work_keys_str_mv | AT fulopbarbara il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT hunyadyagnes il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT benczenoemi il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT kormosviktoria il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT szentesnikolett il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT denesadam il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT lenartnikolett il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT borbelyeva il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice AT helyeszsuzsanna il1mediateschronicstressinducedhyperalgesiaaccompaniedbymicrogliaandastrogliamorphologicalchangesinpainrelatedbrainregionsinmice |