Nerve growth factor expression is up-regulated in the rat model of l-arginine-lnduced acute pancreatitis

Abstract

Background & Aims: In somatic pain models, increases in nerve growth factor (NGF) are linked to the development of pain and hyperalgesia. The aim of this study was to examine a rat model of acute necrotizing pancreatitis for changes in NGF expression. Methods; NGF protein and messenger RNA (mRNA) levels in the pancreas were correlated with histopathologic changes during the course of acute necrotizing pancreatitis in rats induced by the intraperitoneal injection of L-arginine. Immunohistochemistry for NGF localization was performed on the pancreatic tissue. Results: Two phases of NGF production were observed in the inflamed pancreas: an early release from pancreatic islets at 2 and 6 hours and a later increase in mRNA (18-fold at maximum) at 3 days and in protein levels (7-fold at maximum) at 5 days coinciding with maximum parenchyma! necrosis. The intense NGF-like immunoreactivity was observed predominantly in the ductal cells in pancreas from rats with pancreatitis at 5 days. Conclusions: The development of acute necrotizing pancreatitis in this model leads to a significant increase in NGF production and appears to shift the major cellular sites of NGF production from the islets to the ductal cells. It is conceivable that NGF production in the inflamed pancreas is responsible for plastic changes in the sensory neurons that mediate peripheral sensitization and contribute to the generation of pain. © 2000 by the American Gastroenterological Association.