The DOI matches its Crossref record; 98 of the 99 references it cites were found in a registry or an index.
β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia
Open accessAbstract
Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of "pharmacological" interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects.
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“Mutant mice that lacked arrestin 3 (b-arrestin 2) exhibited greater analgesia but significantly less antinociceptive tolerance, physical dependence, constipation, and respiratory suppression in response to morphine (Raehal and Bohn, 2014).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Raehal and Bohn, 2014
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BackgroundInfluentialSelf-citationIncreased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
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Strang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639
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“This contrasts to the absence of robust physiological evidence for a -arrestin signal from the MOR affecting respiratory function (45).”
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BackgroundChapter 1. Neurocircuitry of Addiction
Koob, G. F., & Volkow, N. D. (2021) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615373970.kb01 · Cited by 236
Metadata
- Authors
- Raehal, K. M., & Bohn, L. M.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Raehal, Kirsten M.
- ORCID
- Bohn, Laura M.
- Venue
- Handbook of Experimental Pharmacology
- Publisher
- Springer Berlin Heidelberg
- Published
- 2013-11-05
- Volume
- 219
- Pages
- 427-443
- ISSN
- 0171-2004 (ISSN-L)
- 1865-0325
- PMC
- PMC4804701
- OpenAlex
- W78722479
- Cited by
- 154
- References
- 99
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 63 · 2020: 13 · 2019: 11 · 2018: 7 · 2017: 15 · 2016: 5 · 2015: 2 · 2014: 3
- FWCI
- 4.36
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Handbook of experimental pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA033073, R01DA031927)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Keywords
- beta-arrestin, mu-opioid receptor, CB1 receptor, opioid analgesia, cannabinoid analgesia, G protein-coupled receptors, biased agonists, G protein signaling, receptor internalization, pain management, opioid side effects
- MeSH terms
- beta-Arrestins, Analgesics, Analgesics, Opioid, Animals, Cannabinoids, Humans, Pain, Drug Design, Receptors, Opioid, mu, Arrestins, Receptors, G-Protein-Coupled, Receptor, Cannabinoid, CB1
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