{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:24Z","timestamp":1787028504616,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:00:00Z","timestamp":1678579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 111-2320-B-001-009"],"award-info":[{"award-number":["MOST 111-2320-B-001-009"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Academia Sinica, Taipei, Taiwan","award":["MOST 111-2320-B-001-009"],"award-info":[{"award-number":["MOST 111-2320-B-001-009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central post-stroke pain is a severe persistent pain disease that affects 12% of stroke survivors (CPSP). These patients may have a cognitive impairment, depression, and sleep apnea, which leave them open to misdiagnosis and mistreatment. However, there has been little research on whether the neurohormone melatonin can effectively reduce pain in CPSP conditions. In the present study, we labeled melatonin receptors in various brain regions of rats. Later, we established a CPSP animal model by intra-thalamic collagenase lesions. After a rehabilitation period of three weeks, melatonin was administered using different doses (i.e., 30 mg\/kg, 60 mg\/kg, 120 mg\/kg) for the following three weeks. Mechanical allodynia, thermal hyperalgesia, and cold allodynia behavioral tests were performed. Immediately after behavioral parameters were tested, animals were sacrificed, and the thalamus and cortex were isolated for biochemical (mitochondrial complexes\/enzyme assays and LPO, GSH levels) and neuroinflammatory (TNF-\u03b1, IL-1\u03b2, IL-6) assessments. The results show that melatonin receptors were abundant in VPM\/VPL regions. The thalamic lesion significantly induced pain behaviors in the mechanical, thermal planters, and cold allodynia tests. A significant decrease in mitochondrial chain complexes (C-I, II, III, IV) and enzymes (SOD, CAT, Gpx, SDH) was observed after the thalamic lesion. While there were significant increases in reactive oxygen species levels, including increases in LPO, the levels of reduced GSH were decreased in both the cortex and thalamus. Proinflammatory infiltration was noticed after the thalamic lesion, as there was a significant elevation in levels of TNF-\u03b1, IL-1\u03b2, and IL-6. Administration of melatonin has been shown to reverse the injury effect dose-dependently. Moreover, a significant increase in C-I, IV, SOD, CAT, and Gpx levels occurred in the CPSP group. Proinflammatory cytokines were significantly reduced by melatonin treatments. Melatonin seems to mediate its actions through MT1 receptors by preserving mitochondrial homeostasis, reducing free radical generation, enhancing mitochondrial glutathione levels, safeguarding the proton potential in the mitochondrial ETC by stimulating complex I and IV activities, and protecting the neuronal damage. In summary, exogenous melatonin can ameliorate pain behaviors in CPSP. The present findings may provide a novel neuromodulatory treatment in the clinical aspects of CPSP.<\/jats:p>","DOI":"10.3390\/ijms24065413","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:36:21Z","timestamp":1678685781000},"page":"5413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Modulation of Melatonin in Pain Behaviors Associated with Oxidative Stress and Neuroinflammation Responses in an Animal Model of Central Post-Stroke Pain"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1747-5094","authenticated-orcid":false,"given":"Tavleen","family":"Kaur","sequence":"first","affiliation":[{"name":"Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang-Ming Chiao Tung University and Academia Sinica, Taipei 11529, Taiwan"},{"name":"Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9794-7302","authenticated-orcid":false,"given":"Andrew","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Psychology, Fo Guang University, Yilan County 26247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Chuang","family":"Shyu","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S1474-4422(09)70176-0","article-title":"Central post-stroke pain: Clinical characteristics, pathophysiology, and management","volume":"8","author":"Klit","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4314\/mmj.v32i3.5","article-title":"The prevalence and management of central post-stroke pain at a hospital in Zimbabwe","volume":"32","author":"Ntsiea","year":"2020","journal-title":"Malawi Med. 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