Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model

• Published in: Journal of headache and pain 2014-03, Vol.15 (1), p.14-8, Article 14
• Main Authors: Greco, Rosaria, Mangione, Antonina Stefania, Sandrini, Giorgio, Nappi, Giuseppe, Tassorelli, Cristina
• Format: Article
• Language: English
• Subjects: Analgesics - administration & dosage; Animals; Cannabinoids - administration & dosage; Disease Models, Animal; Drug Delivery Systems - methods; Internal Medicine; Male; Medicine; Medicine & Public Health; Migraine Disorders - drug therapy; Migraine Disorders - metabolism; Neurology; Pain - drug therapy; Pain - metabolism; Pain Measurement; Pain Medicine; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - metabolism; Research Article
• ISSN: 1129-2369; 1129-2377; 1129-2377
• DOI: 10.1186/1129-2377-15-14

Background Experimental 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. Methods The 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. Results AM1241 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. Conclusion These findings suggest that the pharmacological manipulation of the CB 2 receptor may represent a potential therapeutic tool for the treatment of migraine.