The influence of sensory nerves and CGRP on the pancreatic regeneration after repeated episodes of acute pancreatitis in rats.

Stimulation of capsaicin sensitive nerves or administration of calcitonin g ene-related peptide (CGRP) before induction of acute pancreatitis (AP) atte nuates pancreatic damage, whereas CGRP administration after development of AP aggravates lesion of pancreatic tissue. The aim of this study was to det ermine the effect of prolonged activity of sensory nerves or CGRP administr ation on the pancreatic repair after repeated episodes of AP. Five episodes of acute caerulein-induced pancreatitis (10 mu g/kg/h for 5 h s.c.) were p erformed at weekly intervals in rats receiving either vehicle or capsaicin at the sensory nerve stimulatory dose (0.5 mg/kg, 3 times daily), or CGRP ( 10 mu g/kg, 3 times daily). Two weeks after the last induction of AP morpho logical signs of pancreatic damage, pancreatic blood flow (PBF), serum and pancreatic amylase activity, fecal chymotrypsin activity, pancreatic weight , pancreatic RNA and DNA content, as well as, serum interleukin-1 beta (Il- 1 beta) were assessed. Pancreata of animals receiving vehicle alone showed almost full recovery within two weeks after last episode of pancreatitis in duction. In capsaicin-treated group of rats, we observed the increase in PB F by 44% and in serum Il-1 beta concentration by 91%. The pancreatic amylas e activity, fecal activity of chymotrypsin, pancreatic nucleic acids conten t and DNA synthesis were decreased. In rats treated with CGRP the alteratio ns in PBF, serum Il-1 beta concentration, as well as, in pancreatic and fec al activity of enzymes were similar to capsaicin treated group but less pro nounced. We conclude that prolonged activity of capsaicin-sensitive sensory nerves and the presence of their main mediator-CGRP during pancreatic rege neration after AP leads to pancreatic functional insufficiency typical for chronic pancreatitis.