Fatty Acid Binding Protein Deletion Suppresses Inflammatory Pain through Endocannabinoid/N-Acylethanolamine-Dependent Mechanisms
Open accessAbstract
Background: Fatty acid binding proteins (FABPs) serve as intracellular carriers that deliver endocannabinoids and N-acylethanolamines to their catabolic enzymes. Inhibition of FABPs reduces endocannabinoid transport and catabolism in cells and FABP inhibitors produce antinociceptive and anti-inflammatory effects in mice. Potential analgesic effects in mice lacking FABPs, however, have not been tested. Findings: Mice lacking FABP5 and FABP7, which exhibit highest affinities for endocannabinoids, possessed elevated levels of the endocannabinoid anandamide and the related N-acylethanolamines palmitoylethanolamide and oleoylethanolamide. There were no compensatory changes in the expression of other FABPs or in endocannabinoid-related proteins in the brains of FABP5/7 knockout mice. These mice exhibited reduced nociception in the carrageenan, formalin, and acetic acid tests of inflammatory and visceral pain. The antinociceptive effects in FABP5/7 knockout mice were reversed by pretreatment with cannabinoid receptor 1, peroxisome proliferator-activated receptor alpha, and transient receptor potential vanilloid 1 receptor antagonists in a modality specific manner. Lastly, the knockout mice did not possess motor impairments. Conclusions: This study demonstrates that mice lacking FABPs possess elevated levels of N-acylethanolamines, consistent with the idea that FABPs regulate the endocannabinoid and N-acylethanolamine tone in vivo. The antinociceptive effects observed in the knockout mice support a role for FABPs in regulating nociception and suggest that these proteins should serve as targets for the development of future analgesics.
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Genetic deletion of FABP5 and FABP7 reduces thermal hyperalgesia and edema induced by carrageenan injection.
“Similarly, genetic deletion of FABP5 and FABP7 reduces thermal hyperalgesia and edema induced by carrageenan injection (Kaczocha et al, 2015).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Kaczocha et al, 2015
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Self-citationRoeder, N. M., Powell, A., Hamilton, J. A., Richardson, B., Sharma, A., Sharafshah, A., Blum, K., Pinhasov, A., & Thanos, P. K. (2026) · Neuroscience Letters · doi:10.1016/j.neulet.2026.138558 · Cited by 1 · see citing works
Self-citationEvaluating FABP5 as a Therapeutic Target for Pain Management
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Self-citationMildly Increased Mechanical Nociceptive Sensitivity in REV-ERBα Knock-out Mice
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The Role and Research Progress of the Endocannabinoid System in Neuropathic Pain
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Roles of FABPs on endocannabinoid transport and metabolism
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Fatty Acid-Binding Proteins and Substance Use Disorders: From Lipid Signaling to Therapeutic Targets
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- Authors
- Kaczocha, M., Glaser, S. T., Maher, T., Clavin, B., Hamilton, J., Rourke, J. O., Rebecchi, M., Puopolo, M., Owada, Y., & Thanos, P. K.
- Affiliations
- Stony Brook University (US)
- Kingsborough Community College (US)
- Tohoku University (JP)
- Corresponding author
- Kaczocha, Martin
- Venue
- Molecular Pain
- Publisher
- SAGE Publications
- Published
- 2015-01-01
- Volume
- 11
- Pages
- 52-52
- ISSN
- 1744-8069 (ISSN-L)
- PMC
- PMC4551694
- OpenAlex
- W1962384335
- Cited by
- 68
- References
- 24
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 14 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 8 · 2016: 7
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Pain (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 Institute on Drug Abuse (DA035949)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- fatty acid binding protein, FABP5, FABP7, endocannabinoids, N-acylethanolamines, anandamide, palmitoylethanolamide, oleoylethanolamide, inflammatory pain, visceral pain, antinociception, CB1 receptor, PPARα, TRPV1, analgesic targets, knockout mice
- MeSH terms
- Fatty Acid-Binding Protein 7, Animals, Ethanolamines, Inflammation, Male, Mice, Inbred C57BL, Motor Activity, Neoplasm Proteins, Nerve Tissue Proteins, Pain, Mice, Knockout, Fatty Acid-Binding Proteins, Nociception, Endocannabinoids
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