Stimulation of sensory nerves and CGRP attenuate pancreatic damage in ischemia/reperfusion induced pancreatitis
Artur Dembliński, Zygmunt Warzecha, Piotr Ceranowicz, Jolanta Jaworek, Ryszard Sendur, Anna Knafel, Marcin Dembliński, Jan Bliski, Wiesław W. Pawlik, Romana Tomaszewska, Jerzy Stachura, Stanisław J. Konturek
Med Sci Monit 2003; 9(12): BR418-425
Background:Previous studies have shown that sensory nerves and calcitonin gene-related peptide (CGRP) affect caerulein-induced pancreatitis. The aim of this study was to examine the role of capsaicin-sensitive nerves and the impact of CGRP administration on necrotizing pancreatitis induced by ischemia/reperfusion.Material/Methods:Ablation of sensory nerves was made by capsaicin 10 days before induction of pancreatitis. Acute pancreatitis was induced in rats by limitation of pancreatic blood flow (PBF) followed by reperfusion. Treatment with saline or CGRP (10 µg/kg s.c.) or stimulation of sensory nerves by low doses of capsaicin (0.5 mg/kg s.c.) was performed 1 h before ischemia. After 1 h reperfusion we examined pancreatic blood flow (PBF), plasma amylase and lipase activity, plasma interleukin-1beta (IL-1beta) concentration, pancreatic DNA synthesis and morphological signs of pancreatitis.Results:Ischemia followed by 1 h reperfusion led to induction of necrotizing pancreatitis, manifested by morphological signs of pancreatic damage, decrease in pancreatic DNA synthesis and PBF, as well as an increase in plasma amylase and lipase activity and plasma IL-1beta concentration. Both, treatment with CGRP and stimulation of sensory nerves attenuated pancreatic damage. Ablation of sensory nerves enhanced I/R evoked pancreatic damage. The deleterious effect of deactivation of sensory nerves on I/R-induced pancreatitis was partly reversed by administration of CGRP prior to I/R.Conclusions:Stimulation of sensory nerves protects the pancreas against damage evoked by I/R, whereas ablation of these nerves aggravates tissue damage in the pancreas exposed to I/R. The beneficial effect of sensory nerves is partly dependent on CGRP release.
Keywords: Amylases - blood, Animals, Calcitonin Gene-Related Peptide - pharmacology, Calcitonin Gene-Related Peptide - physiology, Capsaicin - pharmacology, Lipase - blood, Male, Neurons, Afferent - drug effects, Neurons, Afferent - physiology, Pancreas - blood supply, Pancreatitis - etiology, Pancreatitis - physiopathology, Pancreatitis - prevention & control, Rats, Rats, Wistar, Reperfusion Injury - complications