IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice
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Published:2023-03-13
Issue:6
Volume:24
Page:5479
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Fülöp Barbara1, Hunyady Ágnes12, Bencze Noémi1, Kormos Viktória1ORCID, Szentes Nikolett1, Dénes Ádám3, Lénárt Nikolett3ORCID, Borbély Éva1, Helyes Zsuzsanna145
Affiliation:
1. Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of Pécs, H-7624 Pécs, Hungary 2. GSK Vaccines Institute for Global Health, I-53100 Siena, Italy 3. “Momentum” Laboratory of Neuroimmunology, Institute of Experimental Medicine, H-1083 Budapest, Hungary 4. Eotvos Lorand Research Network, Chronic Pain Research Group, University of Pécs, H-7624 Pécs, Hungary 5. National Laboratory for Drug Research and Development, H-1117 Budapest, Hungary
Abstract
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.
Funder
Eötvös Loránd Research Network (Chronic Pain Research Group), Pécs, Hungary, National Brain Research Program 3.0, National Research, Development and Innovation Office— János Bolyai Research Scholarship of the Hungarian Academy of Sciences ÚNKP-21-5 new National Excellence Program of the Ministry for Innovation and Technology National Research, Development and Innovation Fund of Hungary, financed under the EGA-16 European Union New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Funds Research grant of Medical School, University of Pécs
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
1 articles.
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