• Rosaria Greco, Antonina Stefania Mangione, Giorgio Sandrini, Giuseppe Nappi, and Cristina Tassorelli.
• Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C, Mondino" National Neurological Institute, 27100 Pavia, Italy. cristina.tassorelli@mondino.it.
• J Headache Pain. 2014 Mar 17; 15: 14.

BackgroundExperimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine. Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception. However, recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain. Systemic administration of nitroglycerin (NTG) consistently induces spontaneous-like headache attacks in migraneurs; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission. In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia.MethodsThe study was performed in male Sprague-Dawley rats pre-treated with NTG (10 mg/kg, i.p.) or vehicle (4 hours before) and treated with the CB2 agonist AM1241 o dimethylsulfoxide (DMSO) 60 minutes before both the tail flick test and the formalin test.ResultsAM1241 showed a significant analgesic effect in baseline conditions in both tests. Furthermore, when administered 3 hours after NTG administration, AM1241 at both doses significantly reduced the total number of flinches/shakes during phase II of the test.ConclusionThese findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.

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