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

Ann Surg. 2007 Nov;246(5):786-93. doi: 10.1097/SLA.0b013e318070d56e.


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.

MeSH terms

  • Abdominal Pain / etiology*
  • Abdominal Pain / metabolism*
  • Abdominal Pain / pathology
  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neprilysin / genetics
  • Neprilysin / metabolism
  • Pain Measurement
  • Pancreatitis, Chronic / complications*
  • Pancreatitis, Chronic / metabolism*
  • Pancreatitis, Chronic / pathology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Neurokinin-2 / genetics
  • Receptors, Neurokinin-2 / metabolism*
  • Receptors, Neurokinin-3 / genetics
  • Receptors, Neurokinin-3 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tachykinins / genetics
  • Tachykinins / metabolism
  • Time Factors


  • Protein Precursors
  • RNA, Messenger
  • Receptors, Neurokinin-2
  • Receptors, Neurokinin-3
  • Tachykinins
  • preprotachykinin
  • Neprilysin