AM404 decreases Fos-immunoreactivity in the spinal cord in a model of inflammatory pain

Brain Res. 2007 Jun 4:1152:87-94. doi: 10.1016/j.brainres.2007.03.071. Epub 2007 Mar 28.

Abstract

Cannabinoids, such as anandamide, are involved in pain transmission. We evaluated the effects of AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide), an anandamide reuptake inhibitor, monitoring the expression of c-fos, a marker of activated neurons and the pain-related behaviours using formalin test. The study was carried out in an experimental model of inflammatory pain made by a single injection of formalin in rat hind paws. Formalin test showed that the antinociceptive effect of AM404 was evident in phase I. We found that Fos-positive neurons in dorsal superficial and deep laminae of the lumbar spinal cord increased in formalin-injected animals and that AM404 significantly reduced Fos induction. Co-administration of cannabinoid CB(1) receptor antagonist (AM251), cannabinoid CB(2) receptor antagonist (AM630) and transient receptor potential vanilloid type 1 (TRPV-1) antagonist (capsazepine), attenuate the inhibitory effect of AM404 and this effect was higher using cannabinoid CB(2) and vanilloid TRPV-1 receptor antagonists. These results suggest that AM404 could be a useful drug to reduce inflammatory pain in our experimental model and that cannabinoid CB(2) receptor and vanilloid TRPV-1 receptor, and to a lesser extent, the cannabinoid CB(1) receptor are involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / antagonists & inhibitors*
  • Arachidonic Acids / metabolism
  • Arachidonic Acids / pharmacology*
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Endocannabinoids
  • Immunohistochemistry
  • Indoles / pharmacology
  • Inflammation / metabolism
  • Male
  • Pain / immunology
  • Pain / metabolism*
  • Pain Measurement
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / antagonists & inhibitors*
  • Polyunsaturated Alkamides / metabolism
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / physiology

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Indoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-fos
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • AM 251
  • capsazepine
  • Capsaicin
  • iodopravadoline
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide