Adenosine A2A Receptor and Substance P Are Involved in the Neurogenic Pain of Myocardial Infarction

OBJECTIVE: To explore the role of adenosine A2A receptor and substance P in mouse acute myocardial infarction (AMI). STUDY DESIGN: Thirty healthy C57BL/6J (WT) mice and 20 adenosine A2A receptor knockout (KO) mice were divided into 5 groups: Sham group, WT+NS group, WT+SP (Substance P blocker L-703,606) group, KO+NS group, and KO+SP group (10 animals per group). An AMI model was established, and electro-cardiograms and echocardiograms were recorded before and after surgery; serum troponin (cTnl) level was measured by ELISA; and myocardial infarction area was measured by TTC staining. The degree of pain after myocardial infarction of mouse was indirectly evaluated by formalin test; and the level of substance P in myocardial infarcted myocardium was detected by ELISA and RT-PCR tests. RESULTS: Fourteen days after the operation the mouse ECG showed the formation of Q waves, the motion of the left ventricular wall was weakened, and the ejection fraction decreased. The TTC result showed a large area of infarction. Serum cTnl concentration 24 hours after surgery was notably higher than that before surgery, and then after 14 days the cTnl concentration fell back to the preoperative level. The AMI mouse model was successfully constructed. In addition, the comparison with the Sham group, AMI mice (WT+NS group) had a notably higher degree of pain, as well as the level of substance P in myocardial tissue. However, both A2A receptor gene knockout or substance P blockers could reduce the pain and substance P level in mouse AMI. CONCLUSION: Adenosine A2A receptor and sub-stance P are involved in the neurogenic inflammatory pain of angina pectoris, so blocking the excessive activa-tion of adenosine A2A receptor and substance P receptor neurokinin 1 can reduce the degree of angina pectoris, protecting the myocardium.