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Tissue and Serum Levels of Substance P Correlate in Patients with Chronic Pancreatitis
Giuseppe Mascetta1, Fabio Francesco Di Mola1, Federico Selvaggi1,2, Massimo Falconi4, Claudio Bassi4, Nathalia Giese2, Markus W. Buechler2, Helmut M. Friess3, Pierluigi Di Sebastiano*1
1Dpt. of Surgery, IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy; 2Dpt. of General Surgery, University of Heidelberg, Heidelberg, Germany; 3Dpt. of Surgery, Technical University of Munich, Munich, Germany; 4Dpt. of Surgery, University of Verona, Verona, Italy
The pathophysiology of pain in chronic pancreatitis (CP) is still unclear. Recent data suggest a role for neuropeptides such as substance P (SP) and the neuroimmune interaction in the inflammatory process of the pancreas. SP degradation is mediated by the endogenous extracellular metalloenzyme called neutral endopeptidase (NEP). Actually, no data are available regarding the relationship between tissue and serum levels of SP in CP. In this study we aimed to investigate a possible correlation between SP mRNA expression in pancreatic tissue and serum levels of SP in patients undergoing surgical resection for CP and to test the hypothesis that neuroimmune inflammation is a pathogenetic factor in CP.
Materials and Methods: SP and NEP mRNA levels were analyzed by quantitative RT-PCR in pancreatic tissue specimens from 30 patients undergoing pancreatic resection for CP and 8 healthy organ donors. In addition, SP serum levels were determined before and after surgery and in 8 healthy individuals (control group) using an ELISA test.
Results: Quantitative RT-PCR demonstrated increased SP mRNA expression in CP tissues (P<0.05) compared to controls, while NEP mRNA expression showed no significant changes between CP and healthy controls. The SP preoperative serum levels correlated with SP tissue levels in CP patients. After pancreatic resection, the majority of CP patients exhibited a significantly reduced expression of SP serum levels compared with preoperative levels.
Conclusions: The present data show that expression of SP is increased during chronic inflammation whereas NEP tissue levels are unaltered. In the SP pathway, it would appear that NEP is unable to sufficiently degrade the increased amount of SP, which may in part explain the perpetuation of pancreatic inflammation. Removal of pancreatic inflamed tissue, the "pacemaker" of neuroimmune inflammation, resulted in the reduction of the circulating level of SP, supporting the hypothesis of neuroimmune crosstalk in CP. Furthermore the correlation between serum and tissue levels of SP suggest that this neuropeptide might also represent a reliable marker of neurogenic inflammation in CP.
