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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]
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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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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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