{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:42:19Z","timestamp":1786977739080,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sleep apnea is a condition that disrupts physiological homeostasis, leading to neuronal dysfunction and triggering a cascade of neurobiological effects. Individuals with sleep apnea and related disturbances may experience increased anxiety and sensory dysfunction, though these phenomena remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we used a mouse model to examine the effects of sleep apnea\u2010induced intermittent hypoxia (IH) on sensory function and the mechanisms underlying chronic IH. Mice were exposed to chronic IH for 10\u2009days to assess neuronal inflammation and neuronal plasticity changes in key areas such as the spinal cord and periaqueductal grey (PAG) to understand how IH alters sensory conduction pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis revealed that in mice exposed to\n                      <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\n                      , astrocytes and microglia were significantly upregulated in the dorsal and ventral horns of the lower spinal cord, accompanied by elevated cytokine levels (\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20101\u03b2 and\n                      <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\n                      \u2010\u03b1), suggesting an inflammatory response. Moreover, a significant increase in astrocyte cells within the\n                      <jats:styled-content style=\"fixed-case\">PAG<\/jats:styled-content>\n                      was also found. Furthermore, chronic\n                      <jats:styled-content style=\"fixed-case\">IH<\/jats:styled-content>\n                      was associated with increased glutamate receptor subunit\n                      <jats:styled-content style=\"fixed-case\">GluN2B<\/jats:styled-content>\n                      expression in the spinal cord.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings collectively suggest that neuronal inflammation and alterations in synaptic plasticity are central to the development of hyperalgesia in IH\u2010exposed mice. Our results provide crucial mechanistic insights into how IH can induce heightened pain sensitivity and underscore the importance of early therapeutic intervention to address sensory complications in patients with chronic sleep apnoea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Our study is the first to demonstrate that increased glial cells and elevated NMDA GluN2B expression in the spinal cord and PAG may drive sleep\u2010related IH\u2010induced hyperalgesia, linking sleep apnea to heightened pain sensitivity. Targeting central nervous system inflammation or GluN2B receptors could be crucial for mitigating the health impacts of sleep apnea.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70039","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T03:44:23Z","timestamp":1749440663000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intermittent Hypoxia Triggers Glial Cell Activation,\n                    <scp>GluN2B<\/scp>\n                    Receptor Upregulation and Hyperalgesia in a Mouse Model of Sleep Apnea"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-1678","authenticated-orcid":false,"given":"Yen\u2010Chin","family":"Liu","sequence":"first","affiliation":[{"name":"School of Post\u2010Baccalaureate, College of Medicine Kaohsiung Medical University (KMU)  Kaohsiung Taiwan"},{"name":"Department of Anesthesiology Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, KMU  Kaohsiung Taiwan"},{"name":"Department of Anesthesiology, College of Medicine National Cheng Kung University Hospital (NCKU), NCKU  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-123X","authenticated-orcid":false,"given":"Bo\u2010Ya","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Primary Care Medicine, Shuang ho Hospital Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-4701","authenticated-orcid":false,"given":"Kuan\u2010Yi","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Primary Care Medicine, Shuang ho Hospital Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u2010Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"School 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