Chemical pancreatectomy: an unconventional approach to preventing autodigestion in pancreatitis

Due to progressive inflammation, chronic pancreatitis destroys both the exocrine and endocrine pancreas and sensitizes pancreatic nerves, leading to unremitting pain. Unfortunately, there are no treatments for pancreatic inflammation and approaches to ameliorate pain are suboptimal. Pancreatic inflammation is particularly problematic because damage to acinar cells causes local release of digestive enzymes, which initiate pancreatic autodigestion. The combination of autodigestion and inflammation is unique to pancreatitis and undoubtedly contributes to the difficulty in devising effective treatments. In this issue of the JCI, Saleh et al. describe a nonsurgical technique to ablate pancreatic acinar cells, thus eliminating the source of digestive enzymes and preventing autodigestion. In mice and a nonhuman primate model, this approach effectively reduced inflammation and pain while preserving islet cell function. These findings support the concept that ongoing acinar cell damage is at the root of chronic pancreatitis and provide a possible strategy for clinical treatment.