Actions of N-arachidonyl-glycine in a rat neuropathic pain model

Neuropharmacology. 2008 Jan;54(1):189-93. doi: 10.1016/j.neuropharm.2007.05.004. Epub 2007 May 18.

Abstract

While cannabinoid receptor agonists reduce the abnormal pain sensations associated with animal models of neuropathic pain states they also produce CB(1) receptor mediated side effects. Recently, a number of arachidonic acid-amino acid conjugates, including N-arachidonyl-glycine (NAGly), have been identified which are structurally related to the endocannabinoid arachidonyl ethanolamide (anandamide). In the present study we examined the effect of NAGly in a rat model of neuropathic pain. Intrathecal administration of NAGly (700 nmol) and the pan-cannabinoid receptor agonist HU-210 (30 nmol) reduced the mechanical allodynia induced by partial ligation of the sciatic nerve. The NAGly induced anti-allodynia was dose dependent and, unlike HU-210, was unaffected by the cannabinoid CB(1) and CB(2) receptor antagonists, AM251 and SR144528 (30 nmol). The NAGly degradation products, arachidonic acid and glycine (700 nmol), did not reduce allodynia. HU-210, but not NAGly produced a reduction in rotarod latency. These findings suggest that NAGly may provide a novel analgesic approach to alleviate neuropathic pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Arachidonic Acids / therapeutic use*
  • Area Under Curve
  • Camphanes / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives
  • Dronabinol / therapeutic use
  • Glycine / analogs & derivatives*
  • Glycine / therapeutic use
  • Hyperalgesia / drug therapy
  • Hyperalgesia / etiology
  • Male
  • Pain Measurement / methods
  • Piperidines / administration & dosage
  • Pyrazoles / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Sciatica / drug therapy*
  • Sciatica / physiopathology

Substances

  • Analgesics
  • Arachidonic Acids
  • Camphanes
  • N-arachidonylglycine
  • Piperidines
  • Pyrazoles
  • SR 144528
  • AM 251
  • Dronabinol
  • HU 211
  • Glycine