title: Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.
abstract: 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.
  
  
  CONCLUSIONS
  These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Greco
authors.forename: Antonina Stefania
authors.initials: AS
authors.lastname: Mangione
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sandrini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C, Mondino" National Neurological Institute, 27100 Pavia, Italy. cristina.tassorelli@mondino.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tassorelli
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*
chemical_list: C439263:AM 1241; D000700:Analgesics; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2