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Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain\u2010associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) in alleviating pain\u2010associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety\u2010like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress\u2010related hormones including corticosterone, corticotropin\u2010releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    ) is reduced after propofol treatment. Interestingly, artificially activating PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    neurons through chemogenetics interfered with the anxiety\u2010reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of\n                    <jats:italic>\u03b3<\/jats:italic>\n                    \u2010aminobutyric acid type A receptor\n                    <jats:italic>\u03b2<\/jats:italic>\n                    3 (GABA\n                    <jats:sub>A<\/jats:sub>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    3) subunits in PVN\n                    <jats:sup>CRH<\/jats:sup>\n                    neurons diminished the anxiety\u2010relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain\u2010associated anxiety\u2010like behaviors using a single dose of propofol.\n                  <\/jats:p>","DOI":"10.1002\/advs.202309059","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T07:23:43Z","timestamp":1713511423000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Propofol Alleviates Anxiety\u2010Like Behaviors Associated with Pain by Inhibiting the Hyperactivity of PVN\n                    <sup>CRH<\/sup>\n                    Neurons via GABA\n                    <sub>A<\/sub>\n                    Receptor\n                    <i>\u03b2<\/i>\n                    3 Subunits"],"prefix":"10.1002","volume":"11","author":[{"given":"Le","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Anhui Medical University  Hefei 230601 China"},{"name":"Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaona","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai 201210 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Anhui Medical University  Hefei 230601 China"},{"name":"Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes Anhui Medical University  Hefei 230032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology ShanghaiTech University  Shanghai 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