Alcohol abuse is a major cause of
pancreatitis in people, but the mechanism is unknown. It has been recently demonstrated that transient receptor potential vanilloid 1 (TRPV1) activation causes
neurogenic inflammation and plays an important role in
acute pancreatitis. Moreover, TRPV1 is activated by
ethanol. We examined the direct effects of
ethanol on
acute pancreatitis. Acute
inflammation of the pancreas was produced by injection of
ethanol and
palmitoleic acid (POA), a nonoxidative metabolite of
ethanol, in wild-type C57BL/6J mice and Trpv1-knockout C57BL/6J mice. Inflammatory indexes were analyzed 24 h later. Injection of
ethanol + POA produced
acute pancreatitis indicated by significant increases in histopathological damage, serum
amylase levels, and pancreatic MPO concentrations (P<0.05-0.001). All parameters of
pancreatitis were blocked by pretreatment with the TRPV1 antagonist
drug AMG9810. In addition,
ethanol + POA administration to Trpv1knockout mice did not produce pancreatic
inflammation. Treatment with vehicle,
ethanol alone, or POA alone had no inflammatory effects. TRPV1 partially mediates
inflammation induced by
ethanol + POA in the mouse pancreas, consistent with the ability of
ethanol to activate TRPV1. We propose that
ethanol may contribute to alcohol-induced
pancreatitis by a neurogenic mechanism.