{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:51:26Z","timestamp":1773337886548,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T00:00:00Z","timestamp":1666742400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa\u2010 or Cane\u2010mediated nongenomic and genomic effects on mechanical nociception and inflammation\u2010induced changes in interleukin\u20106 (IL\u20106) mediated signaling pathway in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague\u2013Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and\/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL\u20106, IL\u20106R\u03b1, JAK2, pJAK2, STAT3, pSTAT3\n                      <jats:sup>Ser727<\/jats:sup>\n                      , migration inhibitory factor, and cyclooxygenase\u20102 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL\u20106. The competition binding assay was carried out using enzyme\u2010linked immunosorbent assays (ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Administration of Dexa and Cane dose\u2010dependently attenuated FCA\u2010induced inflammatory pain. The sub\u2010additive effect of Dexa\/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL\u20106, pJAK2, and pSTAT3\n                      <jats:sup>Ser727<\/jats:sup>\n                      . The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR\n                      <jats:sup>138<\/jats:sup>\n                      binding site of IL\u20106 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL\u20106 than Cane.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There was no additive or negative effect of Dexa and Cane, and they modulate the IL\u20106\/JAK2\/STAT3 signaling pathway through competitive binding with IL\u20106 and relieves hypersensitivity during inflammatory pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.721","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T05:11:00Z","timestamp":1666761060000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL\u20106\/JAK2\/STAT3 signaling pathway during inflammatory pain in vivo and in vitro"],"prefix":"10.1002","volume":"10","author":[{"given":"Jie","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Guangzhou University 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