Nerve growth factor and its high-affinity receptor in chronic pancreatitis

Helmut Friess, Zhao Wen Zhu, Fabio F. Di Mola, Christoph Kulli, Hans U. Graber, Åke Andren-Sandberg, Arthur Zimmermann, Murray Korc, Max Reinshagen, Markus W. Büchler

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Objective: To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). Summary Background Data: Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. Methods: Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. Results: By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p <0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p <0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). Conclusion: Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.

Original languageEnglish (US)
Pages (from-to)615-624
Number of pages10
JournalAnnals of Surgery
Volume230
Issue number5
DOIs
StatePublished - Nov 1999
Externally publishedYes

Fingerprint

Chronic Pancreatitis
Receptor Protein-Tyrosine Kinases
Nerve Growth Factor
Messenger RNA
Acinar Cells
In Situ Hybridization
Peripheral Nerves
Pain
Northern Blotting
Growth
Growth and Development
Ganglia
Pancreas
Fibrosis
Immunohistochemistry
Staining and Labeling
Survival

ASJC Scopus subject areas

  • Surgery

Cite this

Friess, H., Zhu, Z. W., Di Mola, F. F., Kulli, C., Graber, H. U., Andren-Sandberg, Å., ... Büchler, M. W. (1999). Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Annals of Surgery, 230(5), 615-624. https://doi.org/10.1097/00000658-199911000-00002

Nerve growth factor and its high-affinity receptor in chronic pancreatitis. / Friess, Helmut; Zhu, Zhao Wen; Di Mola, Fabio F.; Kulli, Christoph; Graber, Hans U.; Andren-Sandberg, Åke; Zimmermann, Arthur; Korc, Murray; Reinshagen, Max; Büchler, Markus W.

In: Annals of Surgery, Vol. 230, No. 5, 11.1999, p. 615-624.

Research output: Contribution to journalArticle

Friess, H, Zhu, ZW, Di Mola, FF, Kulli, C, Graber, HU, Andren-Sandberg, Å, Zimmermann, A, Korc, M, Reinshagen, M & Büchler, MW 1999, 'Nerve growth factor and its high-affinity receptor in chronic pancreatitis', Annals of Surgery, vol. 230, no. 5, pp. 615-624. https://doi.org/10.1097/00000658-199911000-00002
Friess H, Zhu ZW, Di Mola FF, Kulli C, Graber HU, Andren-Sandberg Å et al. Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Annals of Surgery. 1999 Nov;230(5):615-624. https://doi.org/10.1097/00000658-199911000-00002
Friess, Helmut ; Zhu, Zhao Wen ; Di Mola, Fabio F. ; Kulli, Christoph ; Graber, Hans U. ; Andren-Sandberg, Åke ; Zimmermann, Arthur ; Korc, Murray ; Reinshagen, Max ; Büchler, Markus W. / Nerve growth factor and its high-affinity receptor in chronic pancreatitis. In: Annals of Surgery. 1999 ; Vol. 230, No. 5. pp. 615-624.
@article{44392d93d959446097e75ee56d0d33d4,
title = "Nerve growth factor and its high-affinity receptor in chronic pancreatitis",
abstract = "Objective: To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). Summary Background Data: Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. Methods: Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. Results: By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42{\%} (13.1-fold) and 54{\%} (5.5-fold) of the CP samples (p <0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p <0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). Conclusion: Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.",
author = "Helmut Friess and Zhu, {Zhao Wen} and {Di Mola}, {Fabio F.} and Christoph Kulli and Graber, {Hans U.} and {\AA}ke Andren-Sandberg and Arthur Zimmermann and Murray Korc and Max Reinshagen and B{\"u}chler, {Markus W.}",
year = "1999",
month = "11",
doi = "10.1097/00000658-199911000-00002",
language = "English (US)",
volume = "230",
pages = "615--624",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Nerve growth factor and its high-affinity receptor in chronic pancreatitis

AU - Friess, Helmut

AU - Zhu, Zhao Wen

AU - Di Mola, Fabio F.

AU - Kulli, Christoph

AU - Graber, Hans U.

AU - Andren-Sandberg, Åke

AU - Zimmermann, Arthur

AU - Korc, Murray

AU - Reinshagen, Max

AU - Büchler, Markus W.

PY - 1999/11

Y1 - 1999/11

N2 - Objective: To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). Summary Background Data: Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. Methods: Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. Results: By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p <0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p <0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). Conclusion: Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.

AB - Objective: To study the mechanisms that are involved in nerve growth and contribute to pain generation in chronic pancreatitis (CP). Summary Background Data: Chronic pancreatitis is a painful disease associated with characteristic nerve changes, including an increase in nerve number and diameter. The mechanisms that influence nerve growth are not known. Nerve growth factor (NGF) and its high-affinity tyrosine kinase receptor A (TrkA) are involved in neural development and survival and growth of central and peripheral nerves. Methods: Nerve growth factor and TrkA were investigated by Northern blot analysis, in situ hybridization, and immunohistochemical staining in the pancreases of 24 patients with CP, and the findings were correlated with clinical parameters. Results: By Northern blot analysis, NGF and TrkA mRNA expression were increased in 42% (13.1-fold) and 54% (5.5-fold) of the CP samples (p <0.01), respectively. In situ hybridization revealed that in CP, enhanced NGF mRNA expression was present in metaplastic ductal cells, in degenerating acinar cells, and in acinar cells dedifferentiating into tubular structures. TrkA mRNA was intensely present in the perineurium. Further, enhanced NGF and TrkA mRNA signals were also present in intrapancreatic ganglia cells in CP samples. Immunohistochemistry confirmed the in situ hybridization findings. Analysis of the molecular findings with clinical parameters revealed a significant relation (p <0.05) between NGF mRNA levels and pancreatic fibrosis (r = 0.64) and acinar cell damage (r = 0.74) and between TrkA mRNA and pain intensity (r = 0.84). Conclusion: Activation of the NGF/TrkA pathway occurs in CP. It might influence neural morphologic changes and the pain syndrome in this disorder.

UR - http://www.scopus.com/inward/record.url?scp=19244385562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19244385562&partnerID=8YFLogxK

U2 - 10.1097/00000658-199911000-00002

DO - 10.1097/00000658-199911000-00002

M3 - Article

C2 - 10561084

AN - SCOPUS:19244385562

VL - 230

SP - 615

EP - 624

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 5

ER -