{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:23:55Z","timestamp":1779211435150,"version":"3.51.4"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The \u03b12-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the \u03b12-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, \u03b12-adrenoceptor mRNA expression was significantly upregulated, and \u03b12-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular\u2013mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25\u00a0h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the \u03b12-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.<\/jats:p>","DOI":"10.3389\/fphar.2024.1359319","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T05:12:17Z","timestamp":1710997937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Alpha 2-adrenoceptor participates in anti-hyperalgesia by regulating metabolic demand"],"prefix":"10.3389","volume":"15","author":[{"given":"Ke","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Qing","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxia","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Zhuo","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Kun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao-Qiong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41586-019-0920-1","article-title":"The CH25H-CYP7B1-ROR\u03b1 axis of cholesterol metabolism regulates osteoarthritis","volume":"566","author":"Choi","year":"2019","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1097\/j.pain.0000000000002078","article-title":"Large-scale functional ultrasound imaging of the spinal cord reveals in-depth spatiotemporal responses of spinal nociceptive circuits in both normal and inflammatory states","volume":"162","author":"Claron","year":"2021","journal-title":"Pain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s12640-020-00257-2","article-title":"Neuropathic pain: the dysfunction of Drp1, mitochondria, and ROS homeostasis","volume":"38","author":"Dai","year":"2020","journal-title":"Neurotox. 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