Primary sensory neurons: a common final pathway for inflammation in experimental pancreatitis in rats.
We hypothesized that neurogenic inflammation is a common final pathway for parenchymal inflammation in pancreatitis and evaluated the role of primary sensory neurons in secretagogue-induced and obstructive pancreatitis. Neonatal rats received either the primary sensory neuron-denervating agent capsaicin (50 mg/kg s.c.) or vehicle. At 8 wk of age, pancreatitis was produced by six hourly injections of caerulein (50 microg/kg i.p.) or by common pancreaticobiliary duct ligation (CPBDL). The severity of pancreatitis was assessed by serum amylase, pancreatic myeloperoxidase (MPO) activity, histological grading, pancreatic plasma extravasation, and wet-to-dry weight ratio. Caerulein significantly increased MPO activity and wet-to-dry weight ratio, produced histological evidence of edematous pancreatitis, induced plasma extravasation, and caused hyperamylasemia. CPBDL increased MPO activity and produced histological evidence of pancreatitis. Neonatal capsaicin administration significantly reduced tissue MPO levels, histological severity scores, and wet-to-dry weight ratio and abolished plasma extravasation. These results demonstrate that primary sensory neurons play a significant role in the inflammatory cascade in experimental pancreatitis and appear to constitute a common final pathway for pancreatic parenchymal inflammation.
Nathan
Jaimie D
JD
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Peng
Ruth Y
RY
Wang
Yu
Y
McVey
Douglas C
DC
Vigna
Steven R
SR
Liddle
Rodger A
RA
D000681:Amylases / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001652:Bile Ducts / Q000601:surgery; D002211:Capsaicin / Q000008:administration & dosage; D002108:Ceruletide / Q000008:administration & dosage; D003714:Denervation; D008026:Ligation; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D010179:Pancreas / Q000201:enzymology / Q000294:innervation* / Q000473:pathology; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D009195:Peroxidase / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D002108:Ceruletide; D009195:Peroxidase; D000681:Amylases; D002211:Capsaicin