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.