{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:28:28Z","timestamp":1767245308306,"version":"3.48.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Five years after the onset of the SARS-CoV-2 pandemic, post-COVID-19 condition continues to affect millions of subjects with persistent symptoms that significantly impair quality of life. Post-COVID-19 pain, particularly in women, has emerged as a frequent yet underestimated symptom. The validation and identification of animal models that reproduce persistent symptoms after an acute SARS-CoV-2 infection is crucial for a better understanding of the underlying mechanisms. The aim of the current study was to evaluate thermal nociception, biomarkers of inflammation, and nerve tissue damage in a female animal model of post-COVID-19 condition. A SARS-CoV-2 infection model was established by intranasal administration of the Omicron variant (BA.1.17 lineage) in transgenic female C57BL\/6 mice expressing the human ACE2 receptor (hACE2). Nociception was assessed using the hot-plate test for 28 days post-infection. Afterwards, animals were sacrificed to analyze plasma inflammatory biomarkers by multiplex analysis. In addition, IL-6, IL-18, and IL-1\u03b2 expression were evaluated by immunohistochemistry to analyze neural inflammation in the saphenous nerve. The results revealed that heat nociceptive thresholds in infected mice did not significantly differ from those of non-infected, but a trend toward lower thresholds was observed in the infected group (days 14 and 28 post-infection). In addition, a slight modification in pro- and anti-inflammatory cytokines\/chemokines in plasma was detected, but no changes in the expression of IL-6, IL-1\u03b2, or IL-18 were observed in the saphenous nerve. Based on all the analyses conducted, infection with the Omicron variant of SARS-CoV-2 did not induce thermal sensitization in animals nor alterations in the expression of inflammatory biomarkers in the saphenous nerve. Finally, a slight state of systemic inflammation was present in the infected animals. The absence of detectable changes in this animal model underscores the need for further research to clarify the discrepancies observed in human patients and to explore alternative pathways potentially involved in post-COVID-19 pain syndromes.<\/jats:p>","DOI":"10.3390\/ijms27010359","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:05:01Z","timestamp":1767193501000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Nociception and Inflammatory\/Tissue Damage Biomarkers in a Post-COVID-19 Animal Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-2750","authenticated-orcid":false,"given":"Eva M.","family":"S\u00e1nchez-Robles","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8789-9869","authenticated-orcid":false,"given":"Carmen","family":"Rodr\u00edguez-Rivera","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-4446","authenticated-orcid":false,"given":"Nancy","family":"Paniagua Lora","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-6283","authenticated-orcid":false,"given":"Esperanza","family":"Herrad\u00f3n Pliego","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-6934","authenticated-orcid":false,"given":"Carlos","family":"Goicoechea Garcia","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0892-1579","authenticated-orcid":false,"given":"Lars","family":"Arendt-Nielsen","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Gastroenterology & Hepatology, Mech-Sense, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"},{"name":"Steno Diabetes Center North Denmark, Clinical Institute, Aalborg University Hospital, DK-9000 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3772-9690","authenticated-orcid":false,"given":"Cesar","family":"Fern\u00e1ndez-de-las-Pe\u00f1as","sequence":"additional","affiliation":[{"name":"Center for Neuroplasticity and Pain (CNAP), Sensory-Motor Interaction (SMI) Center, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark"},{"name":"Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1378-0387","authenticated-orcid":false,"given":"Visitaci\u00f3n","family":"L\u00f3pez-Miranda","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"Unidad Asociada al Instituto de Qu\u00edmica Medica (IQM) del Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"},{"name":"High Performance Research Group in Experimental Pharmacology (Pharmakom-URJC), Universidad Rey Juan Carlos, 28922 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, December 10). 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