Transient Receptor Potential Vanilloid 1 Mediates Laporotomy and Opioid-induced Infarct Size Reduction in Rats

Abstract

Background: In light of an opioid epidemic in the United States, physicians are increasingly prescribing non-opioid analgesics. However, newer pain medications such as transient receptor potential vanilloid 1 (TRPV1) inhibitors may impede organ protection. We examined in rodents whether a laparotomy- and morphine-induced infarct size reduction is mediated by TRPV1. Further, we tested if inhibiting TRPV1 interferes with laparotomy- or morphine-induced cardioprotection. Methods: Male Sprague-Dawley rats were subjected to 30 minutes of coronary occlusion followed by 120 minutes reperfusion. Before ischaemia, a laparotomy with or without application of capsaicin cream (0.1%, a TRPV1 activator), was performed. Additional sets of rats were given morphine (3 mg/kg) with or without capsaicin. Further, capsazepine (3 mg/kg, a classical TRPV1 inhibitor), and P5 (3 mg/kg, a peptide analgesic and TRPV1 inhibitor), were given prior to the laparotomy or morphine. Myocardial infarct size was determined. Results: A laparotomy or capsaicin reduced infarct size versus controls (to 44±2%* or 49±1%* vs. 66±1%, infarct size/area at risk %, n=6, *P<0.0001). When combining laparotomy and capsaicin, cardioprotection was not additive. Morphine also reduced infarct size (37±3%* vs. 61±2%, n=6, P<0.0001), with no additive effect when combined with capsaicin. The TRPV1 inhibitors capsazepine and P5 abolished cardioprotection induced by either a laparotomy (58±1%+ and 65±2%+ vs. 44±2%+, respectively) or morphine (62±3%+ and 58±2%+ vs. 37±3%, respectively, n=6, +P<0.0001). Conclusions: Infarct size reduction by a laparotomy or morphine is blocked by inhibiting TRPV1. Drugs given which inhibit TRPV1 may impede organ protection and this requires further study.