Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats

芬太尼可改善大鼠坏死性急性胰腺炎的严重程度,而吗啡或丁丙诺啡则不能

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作者:Emese Réka Bálint, Gabriella Fűr, Balázs Kui, Zsolt Balla, Eszter Sára Kormányos, Erik Márk Orján, Brigitta Tóth, Gyöngyi Horváth, Edina Szűcs, Sándor Benyhe, Eszter Ducza, Petra Pallagi, József Maléth, Viktória Venglovecz, Péter Hegyi, Lóránd Kiss, Zoltán Rakonczay Jr

Abstract

Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.

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