The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Inhibition of Fatty Acid Binding Proteins Elevates Brain Anandamide Levels and Produces Analgesia
Open accessAbstract
The endocannabinoid anandamide (AEA) is an antinociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by fatty acid amide hydrolase (FAAH). Fatty acid binding proteins (FABPs) are intracellular carriers that deliver AEA and related N-acylethanolamines (NAEs) to FAAH for hydrolysis. The mammalian brain expresses three FABP subtypes: FABP3, FABP5, and FABP7. Recent work from our group has revealed that pharmacological inhibition of FABPs reduces inflammatory pain in mice. The goal of the current work was to explore the effects of FABP inhibition upon nociception in diverse models of pain. We developed inhibitors with differential affinities for FABPs to elucidate the subtype(s) that contributes to the antinociceptive effects of FABP inhibitors. Inhibition of FABPs reduced nociception associated with inflammatory, visceral, and neuropathic pain. The antinociceptive effects of FABP inhibitors mirrored their affinities for FABP5, while binding to FABP3 and FABP7 was not a predictor of in vivo efficacy. The antinociceptive effects of FABP inhibitors were mediated by cannabinoid receptor 1 (CB1) and peroxisome proliferator-activated receptor alpha (PPARα) and FABP inhibition elevated brain levels of AEA, providing the first direct evidence that FABPs regulate brain endocannabinoid tone. These results highlight FABPs as novel targets for the development of analgesic and anti-inflammatory 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?
In the citing paper
“The FABP inhibitors SBFI26 and SBFI50 attenuate carrageenan-induced acute paw edema and thermal hyperalgesia (Kaczocha et al, 2014).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Kaczocha et al, 2014
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
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,882
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 · cited 1×
“NAEs activate diverse receptor systems, including cannabinoid and PPARa receptors [12,13].”
BackgroundA peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376
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 · cited 1×
“The Hargreaves test was used to assess thermal hyperalgesia [36].”
An anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083
The Economic Costs of Pain in the United States
Gaskin, D. J., & Richard, P. (2012) · The Journal of Pain · doi:10.1016/j.jpain.2012.03.009 · Cited by 2,359 · cited 1×
“Chronic pain affects approximately fifteen percent of the population [43,44].”
BackgroundFatty acid-binding proteins: role in metabolic diseases and potential as drug targets
Furuhashi, M., & Hotamışlıgil, G. S. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2589 · Cited by 1,811 · cited 1×
“Fatty acid binding proteins (FABPs) comprise a family of small cytoplasmic lipid transport proteins [1].”
BackgroundCravatt, 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 · cited 1×
“(FAAH), the principal NAE hydrolyzing enzyme in mice [8,9,26].”
BackgroundIdentification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism
Cao, H., Gerhold, K. A., Mayers, J. R., Wiest, M. M., Watkins, S. M., & Hotamışlıgil, G. S. (2008) · Cell · doi:10.1016/j.cell.2008.07.048 · Cited by 1,174 · cited 1×
“FABPs regulate a plethora of physiological processes including lipid metabolism, neurite outgrowth, inflammation, sleep, and neuronal signaling [14–20].”
BackgroundSelective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects
Long, J. Z., Li, W., Booker, L., Burston, J. J., Kinsey, S. G., Schlosburg, J. E., Pavón, F. J., Serrano, A., Selley, D. E., Parsons, L. H., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.129 · Cited by 954 · cited 1×
“Quantification of endogenous NAEs and 2-AG were performed as previously described with minor modifications [30].”
Method
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–146 of 146
ten Barge, J. A., van den Bosch, G. E., Slater, R., van den Hoogen, N. J., Reiss, I. K. M., & Simons, S. H. P. (2025) · Pediatric Drugs · doi:10.1007/s40272-024-00676-0 · Cited by 6
“Rodent studies have shown that these inhibitors can decrease visceral pain, with enhanced effects when both FAAH and COX are inhibited [242–245].”
Endocannabinoid Metabolism and Transport as Drug Targets
Ciaramellano, F., Fanti, F., Scipioni, L., Maccarrone, M., & Oddi, S. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2728-0_16 · Cited by 6
Truxillic acid monoamides as fatty acid binding protein 5 inhibitors
Zhu, C., Schutz, L., Jayanetti, K., Takemura, K., Doswell, F., Wang, L., Ojima, I., & Kaczocha, M. (2023) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2023.117464 · Cited by 6
Self-citationSierra, S., Dalmau, D., Higuera, S., Cortés, D., Crespo, O., Jiménez, A. I., Pop, A., Silvestru, C., & Urriolabeitia, E. P. (2021) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.1c01458 · Cited by 6
Ohguro, H., Higashide, M., Nishikiori, N., Ogawa, T., Furuhashi, M., Sato, T., & Watanabe, M. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1634262 · Cited by 5
Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis
Mieczkowski, K., Bakiri, L., Martins, B. S., Matsuoka, K., & Wagner, E. F. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-025-01630-4 · Cited by 5
The Role of Fatty Acid Binding Proteins in Neuropsychiatric Diseases: A Narrative Review
Powell, A., Yamaguchi, N., Lu, H., Pareek, O., Elman, I., Gold, M. S., Pinhasov, A., Blum, K., & Thanos, P. K. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl26812 · Cited by 5
Warren, W. G., Osborn, M., David-Pereira, A., Tsantoulas, C., Xue, W., Yates, A., & O’Sullivan, S. E. (2024) · European Journal of Pain · doi:10.1002/ejp.4718 · Cited by 5
Cabezas, R., Sahebkar, A., Echeverrı́a, V., Santos, J. G., Ashraf, G. M., & Barreto, G. E. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-64872-5_29 · Cited by 5
Myogenic Classical Endocannabinoids, Their Targets and Activity
Balezina, O. P., Tarasova, E. O., & Bogacheva, P. O. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924100080 · Cited by 4
“Involvement of heat shock proteins and fatty acid-binding proteins (FABP) in the intracellular and/or transmembrane transport of ECs has also been proven [43].”
Wang, H., Zhu, C., Swamynathan, M. M., Rajput, S., Jayanetti, K., Rendina, D., Takemura, K., Bogdan, D., Wang, L., Rizzo, R. C., et al. (2025) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2025.118136 · Cited by 4
Self-citationMartin, G. G., Seeger, D. R., McIntosh, A. L., Chung, S., Milligan, S., Landrock, D., Dangott, L. J., Golovko, M. Y., Murphy, E. J., Kier, A. B., et al. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.05.013 · Cited by 4
Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins
Chen, S., Pan, Z., Liu, M., Guo, L., Jiang, X. L., & He, G. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00086 · Cited by 4
Doswell, F., Haley, J. D., & Kaczocha, M. (2024) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.123.002006 · Cited by 4
Self-citationNanì, M. F., Rinaldi, M. M., Miraglia, M., Amico, K. R., Cicco, P. D., & Romano, B. (2025) · Progress in Lipid Research · doi:10.1016/j.plipres.2025.101358 · Cited by 3
Chemical Probes for Investigating the Endocannabinoid System
Hanske, A., Nazaré, M., & Grether, U. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_563 · Cited by 3
Changes in median eminence of fatty acid–binding protein 3 in a mouse model of pain
Tachibana, D., Nakamoto, K., & Tokuyama, S. (2022) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12225 · Cited by 2
Svenningsen, E. B., Ottosen, R. N., Jørgensen, K. B., Nišavić, M., Larsen, C. K., Hansen, B. K., Wang, Y., Lindorff‐Larsen, K., Tørring, T., Hacker, S. M., et al. (2022) · RSC Chemical Biology · doi:10.1039/d2cb00161f · Cited by 3
Chemical Genetic Approaches for the Investigation of Neutral Lipid Metabolism
Doler, C., Schweiger, M., Zimmermann, R., & Breinbauer, R. (2015) · ChemBioChem · doi:10.1002/cbic.201500501 · Cited by 2
A Swath Label-Free Proteomics insight into the Faah−/− Mouse Liver
Hamid, Z., Summa, M., & Armirotti, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-30553-z · Cited by 2
Sierra, S., Dalmau, D., Alegre‐Requena, J. V., Pop, A., Silvestru, C., Marin, M. L., Boscá, F., & Urriolabeitia, E. P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087583 · Cited by 2
Evaluating FABP5 as a Therapeutic Target for Pain Management
Warren, W. G., Osborn, M., Kaczocha, M., Yates, A. S., & O’Sullivan, S. E. (2026) · European Journal of Pain · doi:10.1002/ejp.70267 · Cited by 1
Self-citationLu, H., Roeder, N. M., Richardson, B., Hamilton, J. A., Lagamjis, G., Owada, Y., Kagawa, Y., Sharma, A., & Thanos, P. K. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04753-3 · Cited by 1
Mildly Increased Mechanical Nociceptive Sensitivity in REV-ERBα Knock-out Mice
Lee, J., Ko, H., Kim, K., & Kaang, B. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.6.342 · Cited by 1
“Therefore, inhibition of FABPs has caused analgesia in various pain models [27].”
BackgroundLiang, L., Xu, S., Peng, X., Wang, Z., Le, C., Wu, X., Zeng, Z., Zeng, S., Zhang, C., Qiu, M., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3407631/v1 · Cited by 1
Kidney proteomic profiling of African catfish.
Robak, P., Ozgo, M., Herosimczyk, A., Lepczyński, A., Pyć, A., & Skrzypczak, W. F. (2015) · Medycyna Weterynaryjna
Mina tratatzeko estrategia farmakologiko berriak: kannabinoideak
Aostri, E., Pineda, J., & Mendiguren, A. (2017) · Osagaiz osasun-zientzien aldizkaria · doi:10.26876/osagaiz.2.2017.91
Inactivated Fatty Acid-Binding Protein 5 (FABP5) is a Suppressor for Prostate Cancer
Al-Jameel, W. H., He, G., Jin, X., Zhang, J., Al-Bayati, A. M. S., Platt-Higgins, A. M., PRudland, P. S., & Ke, Y. (2020) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pag.1.2020.8
“com effect of BMS309403, were originally effective analgesics and anti-inflammatory agents in mice [21-23].”
BackgroundThe Role and Research Progress of the Endocannabinoid System in Neuropathic Pain
刘, 雅. (2022) · International Journal of Psychiatry and Neurology · doi:10.12677/ijpn.2022.113004
Roles of FABPs on endocannabinoid transport and metabolism
Duttaroy, A. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95700-7.00029-2
Ojima, I., Wang, H., Zhu, C., Swamynathan, M. M., Rajput, S., Jayanetti, K., Rendina, D., Takemura, K., Bogdan, D., Wang, L., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5105120
Self-citationTian, J.-J., Wei, B., Lou, Y.-P., Xiao, X., & Zhong, F.-F. (2025) · Future Neurology · doi:10.1080/14796708.2025.2542714
Schutz, L., Gordon, C., Hassan, M., Studholme, K. M., Khan, A., Christophides, A. H., Halper, D., Stanley, S. P., Nicholson, J., Bennett‐Guerrero, E., et al. (2025) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000007741
Self-citationEndocannabinoid signaling in glial cells
Baraibar, A. M., Sánchez-Martín, E., Colomer, T., Calovi, S., Bernal-Chico, A., & Mato, S. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00005-0
Uzuneser, T. C., Jones, M. J., Sarikahya, M. H., Gummerson, D., Whitehead, S. N., Hardy, D. B., Rushlow, W. J., & Laviolette, S. R. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107201 · Cited by 1
Lu, Y., Xin, Y., Li, H., Fang, X., Lin, Y., & Zhang, C. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116880
Elgohary, R., & Baraka, S. M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01862-4
“Inhibitors of FABPs, such as SBFI26 and SBFI50, have been demonstrated to decrease thermal hyperalgesia associated paw edema in carrageenan model (Kaczocha et al. 2014 ).”
DOCKweb: a web-based GUI platform for molecular modeling with DOCK6
Pak, S., Boysan, B. T., Allen, W. J., & Rizzo, R. C. (2026) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-026-00855-w
Self-citationMhatre, A., Prasad, A., & Naqvi, S. (2026) · ASPET Discovery · doi:10.1016/j.aspetd.2026.100033
Fatty Acid-Binding Proteins and Substance Use Disorders: From Lipid Signaling to Therapeutic Targets
Powell, A., Yamaguchi, N., Delgado, M., Blum, K., Pinhasov, A., Elman, I., & Thanos, P. K. (2026) · Genes · doi:10.3390/genes17091000
“This elevation in endocannabinoid levels triggers cannabinoid receptors that produce significant pain reduction effects, which highlights SBFI26 as a potent anti-nociceptive agent with mild anti-inflammatory activity in mice [104,114].”
BindingDB Entry 50021299: Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins.
BindingDB (2025) · UC San Diego · doi:10.7270/q2x3533h
BindingDB Entry 50020331: Truxillic acid monoamides as fatty acid binding protein 5 inhibitors.
BindingDB (2024) · UC San Diego · doi:10.7270/q2668jnq
BindingDB Entry 7478: FABP1: A Novel Hepatic Endocannabinoid and Cannabinoid Binding Protein.
BindingDB (2016) · UC San Diego · doi:10.7270/q2ms3rjj
Metadata
- Authors
- Kaczocha, M., Rebecchi, M. J., Ralph, B. P., Teng, Y.-H. G., Berger, W. T., Galbavy, W., Elmes, M. W., Glaser, S. T., Wang, L., Rizzo, R. C., Deutsch, D. G., & Ojima, I.
- Affiliations
- Stony Brook University (US)
- Kingsborough Community College (US)
- Corresponding author
- Kaczocha, Martin
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-04-04
- Volume
- 9
- Issue
- 4
- Pages
- e94200
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3976407
- OpenAlex
- W2057639794
- Cited by
- 142
- References
- 53
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 15 · 2023: 10 · 2022: 12 · 2021: 4 · 2020: 10 · 2019: 14 · 2018: 15 · 2017: 15 · 2016: 10 · 2015: 15 · 2014: 1
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CUNY Academic Works (City University of New York) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (DA032232)
- National Institute on Drug Abuse (DA032232, R01DA035923, DA035923, R01DA016419, DA016419, R21DA032232)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- fatty acid binding protein, anandamide, endocannabinoid system, fatty acid amide hydrolase, FABP5, FABP3, FABP7, antinociception, analgesia, inflammatory pain, visceral pain, neuropathic pain, CB1 receptor, PPARα, N-acylethanolamines
- MeSH terms
- Analgesia, Analgesics, Animals, Arachidonic Acids, Brain, Disease Models, Animal, Hyperalgesia, Male, Models, Molecular, Molecular Conformation, Neuralgia, Protein Binding, Receptor, Cannabinoid, CB1, PPAR alpha, Fatty Acid-Binding Proteins, Mice, Rats, Polyunsaturated Alkamides, Molecular Docking Simulation, 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
