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Transient Receptor Potential Vanilloid 1 Inhibitors Block Laparotomy- and Opioid-induced Infarct Size Reduction in Rats.

Transient Receptor Potential Vanilloid 1 Inhibitors Block Laparotomy- and Opioid-induced Infarct Size Reduction in Rats.
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Heymann HM, Wu Y, Lu Y, Qvit N, Gross GJ, Gross ER,


Heymann HM, Wu Y, Lu Y, Qvit N, Gross GJ, Gross ER, (click to view)

Heymann HM, Wu Y, Lu Y, Qvit N, Gross GJ, Gross ER,

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British journal of pharmacology 2017 10 05() doi 10.1111/bph.14064
Abstract
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.

EXPERIMENTAL APPROACH
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.

KEY RESULTS
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.

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