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

Bálint, Emese Réka and Fűr, Gabriella and Kui, Balázs and Balla, Zsolt and Kormányos, Eszter Sára and Orján, Erik Márk and Tóth, Brigitta and Horváth, Gyöngyi and Szűcs, Edina and Benyhe, Sándor and Ducza, Eszter and Pallagi, Petra and Maléth, József and Venglovecz, Viktória and Hegyi, Péter and Kiss, Lóránd and Rakonczay, Zoltán (2022) Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (3). No. 1192. ISSN 1661-6596

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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 buprenor- phine 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 pretreatment 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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