The DOI matches its Crossref record; 49 of the 53 references it cites were found in a registry or an index.
Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia
Abstract
Although the N-arachidonoyl ethanolamine (anandamide) binds to cannabinoid receptors and has been implicated in the suppression of pain, its rapid catabolism in vivo by fatty acid amide hydrolase (FAAH) has presented a challenge in investigating the physiological functions of this endogenous cannabinoid. In order to test whether anandamide and other non-cannabinoid fatty amides modulate nociception, we compared FAAH (+/+) and (-/-) mice in the tail immersion, hot plate, and formalin tests, as well as for thermal hyperalgesia in the carrageenan and the chronic constriction injury (CCI) models. FAAH (-/-) mice exhibited a CB1 receptor-mediated phenotypic hypoalgesia in thermal nociceptive tests. These mice also exhibited CB1 receptor-mediated hypoalgesia in both phases of the formalin test accompanied with a phenotypic anti-edema effect, which was not blocked by either CB1 or CB2 antagonists. Additionally, FAAH (-/-) mice displayed thermal anti-hyperalgesic and anti-inflammatory effects in the carrageenan model that were mediated, in part, by CB2, but not CB1 receptors. In contrast, no genotype differences in pain behavior were evident following CCI, which was instead found to obliterate the phenotypic hypoalgesia displayed by FAAH (-/-) mice in the tail immersion and hot plate tests, suggesting that nerve injury may promote adaptive changes in these animals. Collectively, these findings demonstrate a cannabinoid receptor-mediated analgesic phenotype in FAAH (-/-) mice. In more general terms, these findings suggest that selective inhibitors of FAAH might represent a viable pharmacological approach for the clinical treatment of pain disorders.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“FAAH inhibitors also attenuate carrageenaninduced edema, an effect that is mediated through the CB 2 receptor (Holt et al, 2005;Lichtman et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Lichtman et al, 2004
In the citing paper
“For example, pharmacological inhibition or genetic deletion of FAAH attenuates carrageenan-induced inflammation as well as mechanical allodynia and thermal hyperalgesia (increased sensitivity to a noxious heat stimuli) (Ghosh et al, 2013;Karbarz et al, 2009;Lichtman et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Lichtman et al, 2004
In the citing paper
“FAAH-/- mice are hypoalgesic in models of acute and inflammatory pain; these effects are blocked by a CB1 antagonist.29, 30”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [30]
In the citing paper
“This basal hypoalgesia is absent in FAAH-/- mice subjected to nerve injury, where genotype differences in evoked neuropathic pain behaviors are not apparent.30”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [30]
Citations
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R. A., Brown, F. J., Flores, C., & Joris, J. L. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,155
Ledent, C. A., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Impérato, A., Pedrazzini, T., Roques, B. P., et al. (1999) · Science · doi:10.1126/science.283.5400.401 · Cited by 3,628
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., et al. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00109-d · Cited by 2,913
2-Arachidonoylgylcerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain
Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2437 · Cited by 2,196
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
Self-citationSR141716A, a potent and selective antagonist of the brain cannabinoid receptor
Rinaldi, M. L., Barth, F., Héaulme, M., Shire, D. J., Calandra, B., Congy, C., Martinez, S., Maruani, J., Neliat, G., Caput, D., et al. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00773-x · Cited by 1,762
Leptin-regulated endocannabinoids are involved in maintaining food intake
Di Marzo, V., Goparaju, S. K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G. I., Palmiter, R. D., Sugiura, T., et al. (2001) · Nature · doi:10.1038/35071088 · Cited by 1,559
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310
Self-citationModulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293
Cited by
Sorted by citations
Items 301–328 of 328
BindingDB (2008) · UC San Diego · doi:10.7270/q2dr2ssh
BindingDB (2008) · UC San Diego · doi:10.7270/q2jh3jgs
BindingDB (2010) · UC San Diego · doi:10.7270/q28s4pzc
BindingDB Entry 50047140: Arylboronic acids as dual-action FAAH and TRPV1 ligands.
BindingDB (2017) · UC San Diego · doi:10.7270/q24f1sm9
BindingDB Entry 50038737: Discovery and development of fatty acid amide hydrolase (FAAH) inhibitors.
BindingDB (2012) · UC San Diego · doi:10.7270/q2j67ht8
BindingDB (2012) · UC San Diego · doi:10.7270/q2qv3ncp
BindingDB (2013) · UC San Diego · doi:10.7270/q2zk5hsk
Targeting the endocannabinoid system to reduce nociception
Booker, L. (2011) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/j2fe-wf53
Cannabinoids for the control of experimental multiple sclerosis
Pryce, G. (2010) · OpenGrey (Institut de l'Information Scientifique et Technique)
Metadata
- Authors
- Lichtman, A. H., Shelton, C. C., Advani, T., & Cravatt, B. F.
- Affiliations
- Scripps Research Institute (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Lichtman, Aron H
- Venue
- Pain
- Published
- 2004-06
- Volume
- 109
- Issue
- 3
- Pages
- 319-327
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2094469214
- Cited by
- 301
- References
- 53
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 14 · 2014: 21 · 2013: 14 · 2012: 23
- FWCI
- 17.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA015197, P01DA009789, R01DA015197, DA‐03672, DA 09789)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- fatty acid amide hydrolase, anandamide, endocannabinoid system, CB1 receptor, CB2 receptor, thermal hyperalgesia, formalin test, chronic constriction injury, nerve injury, analgesic effect, FAAH inhibitors
- MeSH terms
- Fatty Acid Amide Hydrolases, Adaptation, Physiological, Amidohydrolases, Animals, Arachidonic Acids, Disease Models, Animal, Enzyme Inhibitors, Female, Genotype, Inflammation, Male, Pain, Pain Measurement, Peripheral Nerves, Phenotype, Pain Threshold, Mice, Knockout, Somatosensory Disorders, Receptors, Cannabinoid, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Mice, Polyunsaturated Alkamides, Peripheral Nerve Injuries, Cannabinoid Receptor Antagonists, Endocannabinoids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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 ›
Are you an author, or do you see a problem with this page? Request a review
