Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms

Martin Kaczocha, Sherrye T. Glaser, Thomas Maher, Brendan Clavin, John Hamilton, Joseph O'Rourke, Mario Rebecchi, Michelino Puopolo, Yuji Owada, Panayotis K. Thanos

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number52
JournalMolecular Pain
Volume11
Issue number1
DOIs
Publication statusPublished - 2015 Aug 28

Keywords

  • Anandamide
  • Endocannabinoid
  • FABP
  • Fatty acid binding protein
  • Pain

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms'. Together they form a unique fingerprint.

  • Cite this

    Kaczocha, M., Glaser, S. T., Maher, T., Clavin, B., Hamilton, J., O'Rourke, J., Rebecchi, M., Puopolo, M., Owada, Y., & Thanos, P. K. (2015). Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms. Molecular Pain, 11(1), [52]. https://doi.org/10.1186/s12990-015-0056-8