{ "labelLang" : "hun", "responseDate" : "2024-03-28 19:53", "content" : { "otype" : "JournalArticle", "mtid" : 31335696, "status" : "VALIDATED", "published" : true, "comment" : "Funding Agency and Grant Number: Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary of the Semmelweis University; National Research, Development and Innovation Office of Hungary [NKFI FK 124878]; Economic Development and Innovation Operational Programme [GINOP 2.3.2-15-2016-00034]; European Community (EPILA) [QLK6-1999-02334]; Austrian Science FundAustrian Science Fund (FWF) [FWF: I2463-B21]\n Funding text: The work was supported by The Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Neurology Thematic Programme of Semmelweis University (FIKP, 2018) the National Research, Development and Innovation Office of Hungary (NKFI FK 124878), by the Economic Development and Innovation Operational Programme (GINOP 2.3.2-15-2016-00034), the European Community (EPILA, QLK6-1999-02334) and the Austrian Science Fund (FWF: I2463-B21).\nDepartment of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, P.O. Box 370, Budapest, H-1445, Hungary \n Institute of Biochemistry, Biological Research Center, Temesvári krt. 62., Szeged, H-6726, Hungary \n Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum University of Bologna, Via Irnerio 48, Bologna, 40126, Italy \n Department of Pharmaceutical Chemistry, Institut of Pharmacy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck, 6020, Austria \n Cited By :3 \n Export Date: 18 August 2021 \n CODEN: MOLEF \n Correspondence Address: Fürst, S.; Department of Pharmacology and Pharmacotherapy, Nagyvárad tér 4, P.O. 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Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, β-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.", "fundings" : [ { "otype" : "Funding", "mtid" : 2037027, "link" : "/api/funding/2037027", "label" : "(GINOP-2.3.2-15-2016-00034)", "published" : false, "snippet" : true }, { "otype" : "Funding", "mtid" : 2037028, "link" : "/api/funding/2037028", "label" : "(NKFI FK 124878)", "published" : false, "snippet" : true } ], "keywords" : [ { "otype" : "Keyword", "mtid" : 2034, "link" : "/api/keyword/2034", "label" : "ANALGESIA", "published" : true, "oldId" : 2034, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1386520, "link" : "/api/keyword/1386520", "label" : "dysbiosis", "published" : true, "oldId" : 1386520, "snippet" : true }, { "otype" : "Keyword", "mtid" : 2017548, "link" : "/api/keyword/2017548", "label" : "peripheral analgesic tolerance", "published" : true, "snippet" : 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