PMID- 37406874 OWN - NLM STAT- MEDLINE DCOM- 20230829 LR - 20230829 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1817 DP - 2023 Oct 15 TI - Role of magnesium-L-Threonate in alleviating skin/muscle incision and retraction induced mechanical allodynia and anxiodepressive-like behaviors in male rats. PG - 148476 LID - S0006-8993(23)00247-0 [pii] LID - 10.1016/j.brainres.2023.148476 [doi] AB - Chronic postsurgical pain (CPSP) and its emotional comorbidities poses health burden to patients who have received the surgical treatment. However, its underlying mechanism remains unclear. Emerging studies indicate that magnesium deficiency is associated with neurological diseases, and magnesium supplement confers protection under these disease conditions. In this study, we examined the role and mechanism of magnesium deficiency in the pathology of surgery-induced allodynia and negative emotion using a rat model of skin/muscle incision and retraction (SMIR) and investigated the therapeutic effects of magnesium supplementation by oral magnesium-L-Threonate (L-TAMS) in SMIR-injured rats. In the SMIR model, rats developed mechanical allodynia and anxiodepressive-like behaviors. Further, SMIR caused microglia and astrocyte activation and enhanced expression of pro-inflammatory cytokine (TNF-alpha, IL-1beta and IL-6) in the anterior cingulate cortex (ACC). Importantly, magnesium ion (Mg(2+)) levels decreased in the serum and cerebrospinal fluid (CSF) of SMIR-injured rats, which exhibited high correlation with pain and emotion behavioral phenotypes in these rats. Repeated oral administration of L-TAMS increased serum and CSF levels of Mg(2+) in SMIR-injured rats. Notably, L-TAMS administration reversed SMIR-induced mechanical allodynia and anxiodepressive-like behaviors but did not affect pain and emotional behaviors in sham rats. Moreover, L-TAMS administration suppressed SMIR-caused glial activation and proinflammatory cytokine expression in the ACC but had no such effect in sham rats. Together, our study demonstrates the contributing role of magnesium deficiency in the pathology of surgery-induced chronic pain and negative emotion. Moreover, we suggest that L-TAMS might be a novel approach to treat CPSP and its emotional comorbidities. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Chen, Yu AU - Chen Y AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Zhang, Yimeng AU - Zhang Y AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Lin, Wei AU - Lin W AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China; Department of Pediatrics, The First Affiliated Hospital of Fujian Medical University, China. FAU - Tang, Ying AU - Tang Y AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Chen, Liang AU - Chen L AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Gao, Ying AU - Gao Y AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Gao, Guangcheng AU - Gao G AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. FAU - Luo, Xin AU - Luo X AD - Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, China. Electronic address: xin.luo21@hotmail.com. FAU - Chen, Aiqin AU - Chen A AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China. Electronic address: jesseaqc@163.com. FAU - Lin, Chun AU - Lin C AD - Pain Research Institute, Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, China; Department of Pediatrics, The First Affiliated Hospital of Fujian Medical University, China. Electronic address: chunlin77550@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230703 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - NTD0MI8XRT (threonic acid) RN - I38ZP9992A (Magnesium) RN - 0 (Cytokines) SB - IM MH - Rats MH - Male MH - Animals MH - *Hyperalgesia/metabolism MH - Rats, Sprague-Dawley MH - Magnesium/pharmacology MH - *Magnesium Deficiency/complications MH - Cytokines/metabolism MH - Pain/complications MH - Muscles MH - Pain, Postoperative/metabolism OTO - NOTNLM OT - Allodynia OT - Anterior cingulate cortex OT - Chronic postsurgical pain OT - Magnesium-L-Threonate OT - Negative emotion COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/07/06 01:08 MHDA- 2023/08/29 12:44 CRDT- 2023/07/05 19:28 PHST- 2023/04/01 00:00 [received] PHST- 2023/06/29 00:00 [revised] PHST- 2023/07/02 00:00 [accepted] PHST- 2023/08/29 12:44 [medline] PHST- 2023/07/06 01:08 [pubmed] PHST- 2023/07/05 19:28 [entrez] AID - S0006-8993(23)00247-0 [pii] AID - 10.1016/j.brainres.2023.148476 [doi] PST - ppublish SO - Brain Res. 2023 Oct 15;1817:148476. doi: 10.1016/j.brainres.2023.148476. Epub 2023 Jul 3.