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Am J Physiol Gastrointest Liver Physiol ; 327(1): G16-G24, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38651230

RESUMEN

Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. Although typically painful, AP can also be painless. Various agents, including opioids, are used for pain control in AP; the risks and benefits of which are often debated. As experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid, buprenorphine, on the initiation and progression of AP. For this, we administered extended-release buprenorphine subcutaneously before inducing the previously established severe AP model that uses interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days, and parameters of AP induction and progression were compared. Buprenorphine significantly reduced serum amylase, lipase, pancreatic necrosis, and AP-associated fat necrosis, which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP-associated reduction of carotid artery pulse distention and the development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate versus IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers that had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.NEW & NOTEWORTHY Extended-release buprenorphine interferes with the initiation and progression of acute pancreatitis at multiple levels.


Asunto(s)
Buprenorfina , Pancreatitis , Animales , Buprenorfina/farmacología , Pancreatitis/inducido químicamente , Pancreatitis/patología , Ratones , Analgésicos Opioides/farmacología , Modelos Animales de Enfermedad , Masculino , Interleucina-12/metabolismo , Interleucina-18/metabolismo , Interleucina-18/sangre , Ratones Obesos , Enfermedad Aguda , Páncreas/patología , Páncreas/efectos de los fármacos , Ratones Endogámicos C57BL
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