Background: Chronic pancreatitis (CP) is characterized by severe abdominal neuropathic pain, perineural inflammatory cell infiltrations, and intrapancreatic neural growth. Artemin was recently shown to eliminate neuropathic pain and reverse neuro-chemical damage after nerve injury. The role of artemin and its receptor GFRalpha3 was investigated in CP patients.
Methods: The expression of artemin and its receptor GFRalpha3 was studied in CP (n=66) and normal (n=22) pancreatic tissues by QRT-PCR and Western-blot analysis. Artemin expression was correlated with pain, and pathomorphological changes (inflammation, perineural inflammatory cell infiltration, neural alterations and fibrosis). Immunohistochemistry was used to localize artemin and GFRalpha3 in the tissues. To detect sources of artemin, primary human pancreatic stellate cells (hPSCs) were isolated and analysed by QRT-PCR and immunocytology analysis.
Results: In CP, artemin and GFRalpha3 are significantly overexpressed and are located in smooth- muscle cells of arteries, Schwann cells and neural ganglia. Increased levels of artemin-mRNA correlated with pain severity, inflammation, perineural inflammatory cell infiltration, neural density and hypertrophy. Furthermore, the severity of fibrosis was positively related to artemin expression and neural alterations. Activated hPSCs expressed low basal levels of artemin- mRNA which were up-regulated by exposure to TGF-beta1.
Conclusions: Overexpression of artemin in CP might function as a compensatory up-regulation in order to repair neural damage incurred by ongoing pancreatic inflammation. Upregulation of TGF-beta1 seems not only to increase pancreatic fibrosis, but also to contribute to neural alteration by stimulating artemin expression in hPSCs. However, overexpression of endogenous artemin seems not to be sufficient to prevent pain in CP.
- chronic pancreatitis
- neural alteration
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.