Pancreatic neuropathy results in "neural remodeling" and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer.
OBJECTIVE
Chronic pancreatitis (CP) and pancreatic cancer (PCa) are characterized by intrapancreatic neuropathic alterations, including increased neural density and hypertrophy, pancreatic neuritis and neural invasion (NI) by cancer cells in PCa. The aim of this study was to identify the influence of these neuropathic changes on the quality of pancreatic innervation, intrapancreatic glia, and visceral pain.


METHODS
Pancreatic nerve fiber qualities were characterized by immunohistochemical visualization of various markers, including those for sympathetic (tyrosine hydroxylase, TH) and cholinergic innervation (choline acetyltransferase, ChAT), as well as the glial transcription factor, Sox10, and the neuroepithelial progenitor cell marker, Nestin, in normal pancreas (NP, n=16), CP (n=20), and PCa (n=20) patients. The neural immunoreactivity scores of these markers were correlated with the severity of intrapancreatic neuropathic changes and with abdominal pain sensation of patients.


RESULTS
Pancreatic sympathetic innervation was significantly reduced in CP and PCa, whereas parasympathetic innervation did not show major changes. Nestin neuro-immunoreactivity was stronger, and Sox10-immunoreactivity was weaker in CP and PCa than in NP. Pancreatic sympathetic and cholinergic innervation was noticeably decreased in patients with severe pancreatic neuritis, NI by cancer cells, or abdominal pain. Moreover, the neural immunoreactivity for Sox10 and Nestin also varied with intrapancreatic neuropathic alterations and abdominal pain.


CONCLUSIONS
The quality of intrapancreatic nerve fibers and the activation state of intrapancreatic glia in CP and PCa are strikingly different from those in normal pancreas. This novel phenomenon of "neural remodeling" shows how pancreatic neuropathic pain and "visceral neuropathy" are associated with altered pancreatic innervation in CP and PCa.
Ceyhan
Güralp Onur
GO
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich D-81675, Germany. ceyhan@chir.med.tu-muenchen.de
Demir
Ihsan Ekin
IE
Rauch
Ulrich
U
Bergmann
Frank
F
Müller
Michael W
MW
Büchler
Markus W
MW
Friess
Helmut
H
Schäfer
Karl-Herbert
KH
D015746:Abdominal Pain / Q000209:etiology; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009443:Neuritis / Q000473:pathology*; D009473:Neuronal Plasticity; D010147:Pain Measurement; D010179:Pancreas / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000378:metabolism / Q000473:pathology*; D055757:SOXE Transcription Factors / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
D015415:Biomarkers; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors