Stimulation of sensory nerves and CGRP attenuate pancreatic damage in ischemia/reperfusion induced pancreatitis.
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.


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  g/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.
Dembiński
Artur
A
Department of Physiology, Jagiellonian University Medical School, Cracow, Poland. mpdembin@cyf-kr.edu.pl
Warzecha
Zygmunt
Z
Ceranowicz
Piotr
P
Jaworek
Jolanta
J
Sendur
Ryszard
R
Knafel
Anna
A
Dembiński
Marcin
M
Bilski
Jan
J
Pawlik
Wiesław W
WW
Tomaszewska
Romana
R
Stachura
Jerzy
J
Konturek
Stanisław J
SJ
D000681:Amylases / Q000097:blood; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology* / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D008049:Lipase / Q000097:blood; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010179:Pancreas / Q000098:blood supply; D010195:Pancreatitis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications
D008049:Lipase; D000681:Amylases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin