The role of adenosine triphosphate and its receptors in migraine pathophysiology and to develop possible treatment protocols

The Role of Adenosine Triphosphate and Its Receptors In Migraine Pathophysiology and To Develop Possible Treatment Protocols Migraine is a neurovascular disease characterized by recurrent unilateral headache. The dura mater is one of the most important structures in the generation of headaches and it contains many mast cells. Trigeminal innervations of meninges provide a morphological substrate for migraine pain. The fact that ATP lead to pain via its purinoceptors that could play a role in migraine pathophysiology constituted basis of our hypothesis. In the present study, it was aimed to investigate the role of ATP and its receptors in migraine pathophysiology and to develop possible treatment protocols. In the study, suction electrode and Ca+2-imaging methods were used. Rat hemi skulls in artificial cerebrospinal fluid were prepared for electrophysiologic recordings. The preparations were applied ATP (100 µM), ADP (100 µM), AMP (100 µM), adenosine (100 µM), α-β MeATP (20 µM, P2X2, P2X3, P2X2/3 agonist), 2MeSADP (20 µM, P2Y1 agonist), BzATP (100 µM, P2X7 agonist), Suramin (100 µM, P2 antagonist), A-317491 (1 µM, P2X3 antagonist). For Ca+2-imaging, pure neuron and mast cell-neuron co-culture were exposed to ATP (100 µM), Compound 48/80 (10 µg/ml) and Suramin (100 µM). In addition, hemi skulls were exposed ex-vivo to ATP (100 µM) and compound 48/80 (10 µg/ml). The data were compared with t-test by using SPSS 17.0. While ATP and α-β MeATP increased pain spikes (p<0,01); BzATP, 2MeSADP, ADP, AMP and adenosine did not reveal any effect in meninges. ATP increased Ca+2 influx in the neurons (p<0,05). Compound 48/80 increased Ca+2 influx in mast cell-neuron co-culture (p<0,05) and this was blocked by Suramin. Compound 48/80 increased mast cell degranulation and diameters of meningeal arteries (p<0,05). In migraine pathogenesis, while ATP directly plays a role by inducing pain spikes via its P2X2, P2X3 ve P2X2/3 receptors, mast cells take part indirectly through ATP. P2X2, P2X3 ve P2X2/3 receptor antagonists may be new treatment options for migraine headache. Keywords: Migraine, ATP, ATP receptors, pain, nociceptor.