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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-1\u03b1\u03b2-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\u201320% 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.<\/jats:p>","DOI":"10.3390\/ijms24065479","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:04:46Z","timestamp":1678763086000},"page":"5479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["IL-1 Mediates Chronic Stress-Induced Hyperalgesia Accompanied by Microglia and Astroglia Morphological Changes in Pain-Related Brain Regions in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Barbara","family":"F\u00fcl\u00f6p","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"Hunyady","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"GSK Vaccines Institute for Global Health, I-53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi","family":"Bencze","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-2425","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Kormos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolett","family":"Szentes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"D\u00e9nes","sequence":"additional","affiliation":[{"name":"\u201cMomentum\u201d Laboratory of Neuroimmunology, Institute of Experimental Medicine, H-1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-949X","authenticated-orcid":false,"given":"Nikolett","family":"L\u00e9n\u00e1rt","sequence":"additional","affiliation":[{"name":"\u201cMomentum\u201d Laboratory of Neuroimmunology, Institute of Experimental Medicine, H-1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Borb\u00e9ly","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School & Centre of Neuroscience, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"Eotvos Lorand Research Network, Chronic Pain Research Group, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"National Laboratory for Drug Research and Development, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","unstructured":"National Institute for Health and Care Excellence (2021). 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