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Cited by 795Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsNeuropeptides and Animal Physiology

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 access
Hohmann, Andrea G., Suplita, Richard L., Bolton, Nathan M., Neely, Mark H., Fegley, Darren, Mangieri, Regina, Krey, Jocelyn F., Michael Walker, J., Holmes, Philip V., Crystal, Jonathon D., Duranti, Andrea, Tontini, Andrea, Mor, Marco, Tarzia, Giorgio, Piomelli, Daniele·2005·Nature
DOI 10.1038/nature03658
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Abstract

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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  1. Walker, J. M. & Hohmann, A. G. in Cannabinoids—Handbook of Experimental Pharmacology (ed. Pertwee, R.) 509–554 (Springer, Berlin, 2005)

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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
Publisher
Springer Science and Business Media LLC
Published
2005-06
Volume
435
Issue
7045
Pages
1108-1112
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature03658
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
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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