British journal of pharmacology 2017 10 05() doi 10.1111/bph.14064
BACKGROUND AND PURPOSE
In light of the opioid epidemic, physicians are increasingly prescribing non-opioid analgesics to surgical patients. Transient receptor potential vanilloid 1 (TRPV1) inhibitors are potentially alternative pain therapeutics for surgery. Here we examined in rodents whether cardioprotection conferred by two occurrences during surgery, a laparotomy or morphine delivery, is mediated by TRPV1. We further tested whether an experimental analgesic peptide (known as P5) targeted against the TRPV1 C-terminus region interferes with laparotomy- or morphine-induced cardioprotection.
Male Sprague-Dawley rats were subjected to 30 minutes coronary occlusion followed by 120 minutes reperfusion. Before ischaemia, a laparotomy with or without capsaicin application (0.1% cream, a TRPV1 activator) was performed. Additional rats were given morphine (0.3mg·kg(-1) ) with or without capsaicin. Further, capsazepine (3mg·kg(-1) , a classical TRPV1 inhibitor), or P5 (3mg·kg(-1) , a peptide analgesic and TRPV1 inhibitor), were given either alone or prior to a laparotomy or morphine administration. Myocardial infarct size was determined.
A laparotomy, in addition to combining a laparotomy with capsaicin cream, reduced infarct size versus control (44±2*%, 40±2*%, vs. 66±1%, n=6, *P < 0.01). Morphine, in addition to combining morphine administration with capsaicin cream, also reduced infarct size versus control (37±3*%, 43±3*%, vs. 61±2%, n=6, *P < 0.01). When TRPV1 inhibitors capsazepine or P5 were given, either TRPV1 inhibitor abolished the infarct size reduction afforded by a laparotomy or morphine. CONCLUSION AND IMPLICATIONS
Inhibiting TRPV1 blocks laparotomy- or morphine-induced cardioprotection. Impaired organ protection may be a potential pitfall of using TRPV1 inhibitors for pain control.