Anales RANF

P.49 CONTRIBUTION OF P2Y12 RECEPTORS TO ANIMAL MODEL OF NTG-INDUCED MIGRAINE-ASSOCIATED PAIN F. Gölöncsér 1 , L. Otrokocsi 1 , Á. Dénes 1 , B. Sperlágh 1 1 . Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Purinergic receptors are known to regulate different forms of pain as well as migraine headache. To explore the contribution of P2Y12 receptors (P2Y 12 Rs) to migraine pain, we used a nitroglycerin (NTG)-induced mouse model of migraine. Migraine-like pain and behavioral alterations was induced by intraperitoneal NTG (15 mg/kg) in wild-type and P2ry12 gene-deficient ( P2ry12 -/- ) mice. In addition to test the effect of P2Y 12 R inhibition the highly potent and direct-acting P2Y 12 receptor antagonist PSB-0739 was used. NTG induced thermal hyperalgesia, increased head grooming time and caused photophobia in wild-type and P2ry12 -/- mice, followed by the induction of cytokines and c-fos in upper cervical spinal cord and trigeminal nucleus caudalis (TNC). PSB- 0739 (0.3 mg/kg i.t.) reversed thermal hyperalgesia in wild-type mice but had no effect in P2ry12 -/- mice, and it was also effective when applied as a post-treatment. PSB-0739 attenuated the expression of c-Fos in TNC in wild-type mice after NTG treatment. NTG itself did not change ADP-induced platelet activation measured by CD62P upregulation in wild-type mice. Platelet depletion by an anti-mouse CD41 antibody attenuated NTG- induced thermal hypersensitivity and affected pro- and anti-inflammatory cytokine response in wild type mice. In conclusion, P2Y 12 receptors regulate NTG-induced thermal hyperalgesia, the neurogenic inflammatory response, and expression of c-Fos in migraine related areas of the CNS. P2Y12Rs might participate in the pathogenesis of migraine.