AM404, an inhibitor of anandamide reuptake decreases Fos-immunoreactivity in the spinal cord of neuropathic rats after non-noxious stimulation

Eur J Pharmacol. 2005 Jan 31;508(1-3):139-46. doi: 10.1016/j.ejphar.2004.12.031. Epub 2005 Jan 12.

Abstract

Cannabinoids like anandamide are involved in pain transmission. In this study we evaluated the effects of administrating N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404), an inhibitor of anandamide reuptake and monitoring the expression of c-fos, a marker of activated neurons in an experimental model of neuropathic pain (sciatic nerve tying). Fos expression was monitored 14 days after tying of sciatic nerve and 2 h after non-noxious stimulation. We showed that non-noxious stimulation increased Fos-positivity in the dorsal superficial laminae of the lumbar spinal cord of tied animals but not in the control animals. AM404 significantly reduced Fos induction in tied animals. Co-administration of cannabinoid CB1 receptor, cannabinoid CB2 receptor and transient receptor potential vanilloid type 1 (TRPV-1) antagonists reduced the effect of AM404 and this reduction was higher using cannabinoid CB1 receptor antagonist. These results suggest that AM404 could be a useful drug to reduce neuropathic pain and that cannabinoid CB1 receptor, cannabinoid CB2 receptor and vanilloid TRPV-1 receptor are involved.

Publication types

  • Comparative Study
  • 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
  • Constriction
  • Dose-Response Relationship, Drug
  • Endocannabinoids
  • Immunohistochemistry
  • Indoles / pharmacology
  • Male
  • Physical Stimulation
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-fos / analysis*
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiopathology
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism

Substances

  • Arachidonic Acids
  • Endocannabinoids
  • Indoles
  • Piperidines
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-fos
  • Pyrazoles
  • AM 251
  • capsazepine
  • Capsaicin
  • iodopravadoline
  • anandamide
  • N-(4-hydroxyphenyl)arachidonylamide