title: Fatty acid binding protein deletion suppresses inflammatory pain through endocannabinoid/N-acylethanolamine-dependent mechanisms.
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.
  
  
  RESULTS
  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.
authors: Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 117940, USA. martin.kaczocha@stonybrook.edu.
authors: Martin
authors: M
authors: Kaczocha
authors: Department of Biological Sciences, Kingsborough Community College, Brooklyn, NY, 11235, USA. sherrye.glaser@kbcc.cuny.edu.
authors: Sherrye T
authors: ST
authors: Glaser
authors: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794, USA. thomas.maher@stonybrook.edu.
authors: Thomas
authors: T
authors: Maher
authors: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794, USA. brendan.clavin@stonybrook.edu.
authors: Brendan
authors: B
authors: Clavin
authors: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794, USA. john.hamilton@stonybrook.edu.
authors: John
authors: J
authors: Hamilton
authors: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794, USA. joseph.orourke@stonybrook.edu.
authors: Joseph
authors: J
authors: O'Rourke
authors: Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 117940, USA. mario.rebecchi@stonybrookmedicine.edu.
authors: Mario
authors: M
authors: Rebecchi
authors: Department of Anesthesiology, Stony Brook University, Stony Brook, NY, 117940, USA. michelino.puopolo@stonybrookmedicine.edu.
authors: Michelino
authors: M
authors: Puopolo
authors: Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Japan. owada@med.tohoku.ac.jp.
authors: Yuji
authors: Y
authors: Owada
authors: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794, USA. peter.thanos@stonybrook.edu.
authors: Panayotis K
authors: PK
authors: Thanos
mesh_terms: D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency* / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000378:metabolism; D059225:Nociception; D010146:Pain / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D063388:Endocannabinoids; D004983:Ethanolamines; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; C022203:N-acylethanolamines; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins