{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:28Z","timestamp":1787027068179,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010097","name":"China Association for Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Dexmedetomidine (DEX), a selective \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    adrenergic receptor (\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -AR) agonist, has been shown to have peripheral analgesic effects in a variety of pain conditions. However, the precise molecular mechanisms have not yet been fully elucidated. Acid sensing ion channels (ASICs) are the major player in pain associated with tissue acidosis. Given that both \u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -ARs and ASICs exist in dorsal root ganglia (DRG) neurons, we therefore investigated the effects of DEX on the functional activity of ASICs. Herein, whole-cell patch-clamp recordings demonstrated that DEX suppressed ASIC-mediated and acid-evoked currents and action potentials in dissociated rat DRG neurons. DEX shifted downwards concentration-response curve to protons, with a decrease of 35.83 \u00b1 3.91% in the maximal current response to pH 4.5. DEX-induced inhibition of ASIC currents was blocked by the \u03b1\n                    <jats:sub>2A<\/jats:sub>\n                    -AR antagonist BRL44408 in DRG neurons. DEX also inhibited ASIC3 currents in CHO cells co-expressing ASIC3 and \u03b1\n                    <jats:sub>2A<\/jats:sub>\n                    -ARs, but not in ASIC3 transfected CHO cells without \u03b1\n                    <jats:sub>2A<\/jats:sub>\n                    -ARs expression. DEX-induced inhibition of ASIC currents was mimicked by the protein kinase A inhibitor H-89, and blocked by intracellular application of the G\n                    <jats:sub>i\/o<\/jats:sub>\n                    protein inhibitor pertussis toxin and the cAMP analog 8-Br-cAMP. In addition, peripherally administration of DEX dose-dependently relieved nociceptive responses to intraplantar injection of acetic acid in rats through local \u03b1\n                    <jats:sub>2A<\/jats:sub>\n                    -ARs. Our results indicated that DEX inhibited the functional activity of ASICs via \u03b1\n                    <jats:sub>2A<\/jats:sub>\n                    -ARs and intracellular G\n                    <jats:sub>i\/o<\/jats:sub>\n                    proteins and cAMP\/protein kinase A signaling pathway in rat DRG neurons, which was a novel potential mechanism that probably mediated peripheral analgesia of DEX.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.685460","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T02:43:15Z","timestamp":1621824195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Dexmedetomidine Inhibits ASIC Activity via Activation of \u03b12A Adrenergic Receptors in Rat Dorsal Root Ganglion Neurons"],"prefix":"10.3389","volume":"12","author":[{"given":"Shuang","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yu","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Ping","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1097\/00000542-199106000-00005","article-title":"The Effect of Intravenously Administered Dexmedetomidine on Perioperative Hemodynamics and Isoflurane Requirements in Patients Undergoing Abdominal Hysterectomy","volume":"74","author":"Aho","year":"1991","journal-title":"Anesthesiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1007\/bf03018237","article-title":"Dexmedetomidine in Combination with Morphine PCA Provides superior Analgesia for Shockwave Lithotripsy","volume":"51","author":"Alhashemi","year":"2004","journal-title":"Can. 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