The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
An endocannabinoid mechanism for stress-induced analgesia
Open accessAbstract
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.
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“Monoacylglycerol lipase (MGL) is a key enzyme implicated in the hydrolysis of 2-AG.33, 34”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [33]
Citations
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Self-citation
Research works printed but not linked: 1
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Polyunsaturated fatty acids and their metabolites in brain function and disease
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Russo, E. B. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01238.x · Cited by 1,535
Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,595
A Comprehensive Profile of Brain Enzymes that Hydrolyze the Endocannabinoid 2-Arachidonoylglycerol
Blankman, J. L., Simon, G. M., & Cravatt, B. F. (2007) · Chemistry & Biology · doi:10.1016/j.chembiol.2007.11.006 · Cited by 1,177
Metadata
- Authors
- Hohmann, A. G., Suplita, R. L., Bolton, N. M., Neely, M. H., Fegley, D., Mangieri, R., Krey, J. F., Michael Walker, J., Holmes, P. V., Crystal, J. D., Duranti, A., Tontini, A., Mor, M., Tarzia, G., & Piomelli, D.
- Affiliations
- University of Georgia (US)
- University of California, Irvine (US)
- Brown University (US)
- University of Urbino (IT)
- University of Parma (IT)
- Corresponding author
- Hohmann, Andrea G.
- Piomelli, Daniele
- ORCID
- Venue
- Nature
- Published
- 2005-06
- Volume
- 435
- Issue
- 7045
- Pages
- 1108-1112
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2030777873
- Cited by
- 778
- References
- 30
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 22 · 2023: 22 · 2022: 28 · 2021: 26 · 2020: 22 · 2019: 20 · 2018: 29 · 2017: 53 · 2016: 34 · 2015: 38 · 2014: 40 · 2013: 33 · 2012: 45
- FWCI
- 39.98
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- stress-induced analgesia, endocannabinoid system, CB1 receptor, periaqueductal gray, 2-arachidonoylglycerol, anandamide, monoacylglycerol lipase, fatty acid amide hydrolase, opioid-independent analgesia, pain inhibition, stress-related disorders, therapeutic target
- MeSH terms
- Analgesia, Animals, Arachidonic Acids, Biological Transport, Biphenyl Compounds, Glycerides, Hydrolysis, Male, Mesencephalon, Monoacylglycerol Lipases, Stress, Physiological, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Cannabinoid, CB1, Rats, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques
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