The DOI matches its Crossref record; 41 of the 43 references it cites were found in a registry or an index.
Blockade of Endocannabinoid-Degrading Enzymes Attenuates Neuropathic Pain
Open accessAbstract
Direct-acting cannabinoid receptor agonists are well known to reduce hyperalgesic responses and allodynia after nerve injury, although their psychoactive side effects have damped enthusiasm for their therapeutic development. Alternatively, inhibiting fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the principal enzymes responsible for the degradation of the respective endogenous cannabinoids, anandamide (AEA) and 2-arachydonylglycerol (2-AG), reduce nociception in a variety of nociceptive assays, with no or minimal behavioral effects. In the present study we tested whether inhibition of these enzymes attenuates mechanical allodynia, and acetone-induced cold allodynia in mice subjected to chronic constriction injury of the sciatic nerve. Acute administration of the irreversible FAAH inhibitor, cyclohexylcarbamic acid 3'-carbamoylbiphenyl-3-yl ester (URB597), or the reversible FAAH inhibitor, 1-oxo-1-[5-(2-pyridyl)-2-yl]-7-phenylheptane (OL-135), decreased allodynia in both tests. This attenuation was completely blocked by pretreatment with either CB(1) or CB(2) receptor antagonists, but not by the TRPV1 receptor antagonist, capsazepine, or the opioid receptor antagonist, naltrexone. The novel MAGL inhibitor, 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) also attenuated mechanical and cold allodynia via a CB(1), but not a CB(2), receptor mechanism of action. Whereas URB597 did not elicit antiallodynic effects in FAAH(-/-) mice, the effects of JZL184 were FAAH-independent. Finally, URB597 increased brain and spinal cord AEA levels, whereas JZL184 increased 2-AG levels in these tissues, but no differences in either endo-cannabinoid were found between nerve-injured and control mice. These data indicate that inhibition of FAAH and MAGL reduces neuropathic pain through distinct receptor mechanisms of action and present viable targets for the development of analgesic therapeutics.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The cited source says what the claim attributes to it.
In the citing paper
“However, other studies using knockout mice or selective inhibitors of CB 1 or CB 2 receptors show no alterations of nociceptive behavior in neuropathic pain models (Kinsey et al, 2009(Kinsey et al, , 2010) ) though ceiling effects and other methodological differences between studies may have precluded the detection of enhanced nociceptive behavior.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Kinsey et al, 2009
In the citing paper
“though ceiling effects and other methodological differences between studies may have precluded the detection of enhanced nociceptive behavior.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Kinsey et al, 2009
In the citing paper
“Additionally both OL135 and URB597 are antinociceptive in FAAH+/+ mice, but fail to produce an effect in FAAH-/- mice.59”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [59]
In the citing paper
“OL135 and URB597 attenuate cold and mechanical allodynia in a manner that is dependent upon activation of both CB1 and CB2 receptors.59”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [59]
In the citing paper
“The novel MGL inhibitor, JZL184, attenuates CCI-induced mechanical and cold allodynia through indirect activation of the CB1 receptor; JZL184 was efficacious in attenuating neuropathic nociception in both FAAH+/+ and FAAH-/- mice.59”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [59]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,740
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
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
Spared nerve injury: an animal model of persistent peripheral neuropathic pain
Décosterd, I., & Woolf, C. J. (2000) · Pain · doi:10.1016/s0304-3959(00)00276-1 · Cited by 2,317
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-citationGaliègue, S., Mary, S., Marchand, J., Dussossoy, D., Carrière, D., Carayon, P., Bouaboula, M., Shire, D. J., Fur, G. L., & Casellas, P. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20780.x · Cited by 1,776
Identification and Functional Characterization of Brainstem Cannabinoid CB2Receptors
Van Sickle, M. D., Duncan, M., Kingsley, P. J., Mouihate, A., Urbani, P., Mackie, K., Stella, N., Makriyannis, A., Piomelli, D., Davison, J. S., et al. (2005) · Science · doi:10.1126/science.1115740 · Cited by 1,470
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
Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S. E., Allchorne, A. J., Poole, S., Bonventre, J. V., & Woolf, C. J. (2001) · Nature · doi:10.1038/35068566 · Cited by 1,282
Cited by
Sorted by citations
Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system
Schlosburg, J. E., Blankman, J. L., Long, J. Z., Nomura, D. K., Pan, B., Kinsey, S. G., Nguyen, P. T., Ramesh, D., Booker, L., Burston, J. J., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2616 · Cited by 641
Self-citationLipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores
Lass, A., Zimmermann, R., Oberer, M., & Zechner, R. (2010) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.10.004 · Cited by 677
Multiple Functions of Endocannabinoid Signaling in the Brain
Katona, I., & Freund, T. F. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150420 · Cited by 630
The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease
Long, J. Z., & Cravatt, B. F. (2011) · Chemical Reviews · doi:10.1021/cr200075y · Cited by 434
Self-citationLong, J. Z., Nomura, D. K., Vann, R. E., Walentiny, D. M., Booker, L., Jin, X., Burston, J. J., Sim‐Selley, L. J., Lichtman, A. H., Wiley, J. L., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909411106 · Cited by 405
Self-citation
Metadata
- Authors
- Kinsey, S. G., Long, J. Z., O’Neal, S. T., Abdullah, R. A., Poklis, J. L., Boger, D. L., Cravatt, B. F., & Lichtman, A. H.
- Affiliations
- Virginia Commonwealth University (US)
- Scripps Research Institute (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 330
- Issue
- 3
- Pages
- 902-910
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC2729802
- OpenAlex
- W2132380973
- Cited by
- 330
- References
- 43
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 13 · 2023: 8 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 14 · 2018: 21 · 2017: 24 · 2016: 16 · 2015: 21 · 2014: 35 · 2013: 29 · 2012: 33
- FWCI
- 24.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute of International Education
- National Institute on Drug Abuse (DA015197, P01DA009789, DA-017259, R01DA015197, DA009789-11, DA007027-32, P01DA017259, DA 009789, DA015648, T32DA007027, DA007027)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- neuropathic pain, endocannabinoid system, fatty acid amide hydrolase, monoacylglycerol lipase, anandamide, 2-arachidonoylglycerol, CB1 receptor, CB2 receptor, URB597, JZL184, chronic constriction injury, mechanical allodynia, cold allodynia, analgesic drug development
- MeSH terms
- Fatty Acid Amide Hydrolases, Amidohydrolases, Animals, Arachidonic Acids, Benzamides, Carbamates, Cold Temperature, Enzyme Inhibitors, Glycerides, Hyperalgesia, Male, Mice, Inbred C57BL, Monoacylglycerol Lipases, Narcotic Antagonists, Pain, Pain Measurement, Peripheral Nervous System Diseases, Piperidines, Pyridines, Analgesics, Non-Narcotic, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, TRPV Cation Channels, Mice, Benzodioxoles, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, 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
