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

Mol Pain. 2015 Aug 28;11:52. doi: 10.1186/s12990-015-0056-8.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Endocannabinoids / metabolism*
  • Ethanolamines / metabolism*
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins / deficiency*
  • Fatty Acid-Binding Proteins / metabolism
  • Inflammation / complications
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Neoplasm Proteins / deficiency*
  • Neoplasm Proteins / metabolism
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / metabolism
  • Nociception
  • Pain / complications
  • Pain / metabolism*
  • Pain / physiopathology


  • Endocannabinoids
  • Ethanolamines
  • Fabp5 protein, mouse
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • N-acylethanolamines
  • Neoplasm Proteins
  • Nerve Tissue Proteins