Abstract 387: TNF-alpha Contributes to Cardiac Nociception in Myocardial Infarction
Myocardial infarction (MI)-induced cardiac pain is the leading cause of mortality after an acute myocardial infarction. Recent findings from our lab and others suggest that cytokines activated in MI contribute to the pathophysiology of heart disease. Although tumor necrosis factor-alpha (TNF-α) has not been explored in the realm of nociception during acute MI, a large body of literature suggests that TNF-α plays an important role in arthritis and neuropathic pain. In this study, we explored the role played by TNF-α in cardiac nociception after an acute MI. The pain markers measured were cardiac sympathetic afferent discharge, calcitonin gene related peptide (CGRP), and substance P (SP). Adult male rats underwent surgery to induce MI by ligating the left anterior descending coronary artery, or SHAM. ECG was used to confirm myocardial ischemia. Sympathetic afferent discharge was continuously recorded. Rats were subcutaneously treated with the TNF-α inhibitor etanercept (ETN), morphine, or vehicle (VEH). Two hours after MI, rats were sacrificed and the heart and spinal cord at T4 level were collected. Sympathetic afferent discharge significantly increased after coronary artery ligation (CL), and ETN or morphine decreased nerve activity induced by CL. The level of TNF-α in the left ventricle and CGRP and SP in spinal cord laminae I–VII at T4 level in MI rats were higher than SHAM rats. ETN or morphine treatment reversed these changes. These results indicate that increased TNF-α in the heart contributes to cardiac nociception after acute MI. Treatment aimed at blocking the early rise in TNF-α might protect against angina.