Experımental ınvestıgatıon of the role of P2Y12 receptors ın nocıceptıve processes

According to data from the World Health Organization in 2002, has approximately 177 million diabetics and in 2025 this number is expected to reach 300 million. Diabetic patients, depending on the level of the regulation of blood sugar, about half are in the neuropathy. Painful diabetic neuropathy in developed countries is the most common cause neuropathy.Diabetic neuropathy has not been fully understood causes and there is no ideal treatment is still effective. In this thesis, pathophysiology of neuropathic pain possible role of the P2Y12 receptor subtype and selective antagonist of these receptors as potential therapeutic role of clopidogrel and MRS 2395 painful diabetic neuropathy were examined.Dorsal root ganglia (DRG) were removed from 1-2 day old neonatal rats after decapitation and DRG neurones were isolated by enzymatic and mechanical procedures. Fluorescent calcium imaging studies can be made to the effect of clopidogrel and MRS 2395 intracellular free calcium levels were investigated. Both agents dose-dependent as also in the amount of intracellular free calcium led to significantly increased.In in vivo experiments, hot plate analgesimeter was used to determine pain threshold from latency of the nociceptive behavior. clopidogrel and MRS 2395 (1, 10 ve 30 mg/kg) significantly increased the pain threshold when diabetic neuropathy was induced.In conclusion; the widespread use of antithrombotic drug clopidogrel and newly discovered MRS 2395 created an increase in intracellular calcium ratio and increased pain threshold. This finding indicates that, in the treatment of neuropathic pain seems to have potential therapeutic clopidogrel and MRS 2395.