title: Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis.
abstract: 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.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.forename: Carolin
authors.initials: C
authors.lastname: Reiser
authors.forename: Patrick
authors.initials: P
authors.lastname: Fachinger
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Di Sebastiano
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D015746:Abdominal Pain / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D010147:Pain Measurement; D050500:Pancreatitis, Chronic / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D011498:Protein Precursors; D012333:RNA, Messenger; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C044206:preprotachykinin; D015260:Neprilysin