Effects of anandamide in migraine: data from an animal model

J Headache Pain. 2011 Apr;12(2):177-83. doi: 10.1007/s10194-010-0274-4. Epub 2011 Feb 18.


Systemic nitroglycerin (NTG) produces spontaneous-like migraine attacks in migraine sufferers and induces a condition of hyperalgesia in the rat 4 h after its administration. Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine. In this study, the analgesic effect of anandamide (AEA) was evaluated by means of the formalin test, performed in baseline conditions and following NTG-induced hyperalgesia in male Sprague-Dawley rats. AEA was administered 30 min before the formalin injection. In addition, the effect of AEA (administered 30 min before NTG injection) was investigated on NTG-induced Fos expression and evaluated 4 h following NTG injection. AEA induced a significant decrease in the nociceptive behavior during both phases of the formalin test in the animals treated with vehicle, while it abolished NTG-induced hyperalgesia during the phase II. Pre-treatment with AEA significantly reduced the NTG-induced neuronal activation in nucleus trigeminalis caudalis, confirming the results obtained in our previous study, and in area postrema, while the same treatment induced an increase of Fos expression in paraventricular and supraoptic nuclei of the hypothalamus, parabrachial nucleus, and periaqueductal grey. The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a pharmacological modulation of CB receptors can be useful for the treatment of migraine pain.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Arachidonic Acids / pharmacology*
  • Arachidonic Acids / therapeutic use
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cannabinoid Receptor Modulators / pharmacology
  • Cannabinoid Receptor Modulators / therapeutic use
  • Disease Models, Animal
  • Drug Interactions / physiology
  • Endocannabinoids
  • Male
  • Migraine Disorders / drug therapy*
  • Nitroglycerin / antagonists & inhibitors
  • Nitroglycerin / toxicity
  • Pain Measurement / methods
  • Polyunsaturated Alkamides / pharmacology*
  • Polyunsaturated Alkamides / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Treatment Outcome
  • Vasodilator Agents / antagonists & inhibitors
  • Vasodilator Agents / toxicity


  • Analgesics
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Polyunsaturated Alkamides
  • Vasodilator Agents
  • Nitroglycerin
  • anandamide