Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis

Michalski, Christoph W; Shi, Xin; Reiser, Carolin; Fachinger, Patrick; Zimmermann, Arthur; Büchler, Markus W; Di Sebastiano, Pierluigi; Friess, Helmut (2007). Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis. Annals of surgery, 246(5), pp. 786-93. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1097/SLA.0b013e318070d56e

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OBJECTIVE: Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. METHODS: Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. RESULTS: In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. CONCLUSIONS: Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Zimmermann, Arthur
ISSN:	0003-4932
ISBN:	17968170
Publisher:	Lippincott Williams & Wilkins
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:54
Last Modified:	05 Dec 2022 14:16
Publisher DOI:	10.1097/SLA.0b013e318070d56e
PubMed ID:	17968170
Web of Science ID:	000250773400015
URI:	https://boris.unibe.ch/id/eprint/22834 (FactScience: 37243)