Please use this identifier to cite or link to this item:
https://hdl.handle.net/1959.11/30425
Title: | Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO? | Contributor(s): | Gledhil, Laura J (author); Babey, Anna-Marie (author) | Publication Date: | 2021-07 | Early Online Version: | 2021-03-11 | DOI: | 10.1007/s10571-021-01065-8 | Handle Link: | https://hdl.handle.net/1959.11/30425 | Abstract: | The use of morphine as a first-line agent for moderate-to-severe pain is limited by the development of analgesic tolerance. Initially opioid receptor desensitization in response to repeated stimulation, thought to underpin the establishment of tolerance, was linked to a compensatory increase in adenylate cyclase responsiveness. The subsequent demonstration of cross-talk between N-methyl-d-aspartate (NMDA) glutamate receptors and opioid receptors led to the recognition of a role for nitric oxide (NO), wherein blockade of NO synthesis could prevent tolerance developing. Investigations of the link between NO levels and opioid receptor desensitization implicated a number of events including kinase recruitment and peroxynitrite-mediated protein regulation. Recent experimental advances and the identification of new cellular constituents have expanded the potential signaling candidates to include unexpected, intermediary compounds not previously linked to this process such as zinc, histidine triad nucleotide-binding protein 1 (HINT1), micro-ribonucleic acid (mi-RNA) and regulator of G protein signaling Z (RGSZ). A further complication is a lack of consistency in the protocols used to create tolerance, with some using acute methods measured in minutes to hours and others using days. There is also an emphasis on the cellular changes that are extant only after tolerance has been established. Although a review of the literature demonstrates a lack of spatio-temporal detail, there still appears to be a pivotal role for nitric oxide, as well as both intracellular and intercellular cross-talk. The use of more consistent approaches to verify these underlying mechanism(s) could provide an avenue for targeted drug development to rescue opioid efficacy. | Publication Type: | Journal Article | Source of Publication: | Cellular and Molecular Neurobiology, 41(5), p. 927-948 | Publisher: | Springer New York LLC | Place of Publication: | United States of America | ISSN: | 1573-6830 0272-4340 |
Fields of Research (FoR) 2008: | 060111 Signal Transduction | Fields of Research (FoR) 2020: | 310111 Signal transduction | Socio-Economic Objective (SEO) 2008: | 920111 Nervous System and Disorders | Socio-Economic Objective (SEO) 2020: | 200101 Diagnosis of human diseases and conditions | Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
---|---|
Appears in Collections: | Journal Article School of Rural Medicine |
Files in This Item:
File | Description | Size | Format |
---|
SCOPUSTM
Citations
9
checked on Mar 9, 2024
Page view(s)
1,638
checked on Jun 18, 2023
Download(s)
4
checked on Jun 18, 2023
Items in Research UNE are protected by copyright, with all rights reserved, unless otherwise indicated.