Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis.
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.
Michalski
Christoph W
CW
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Shi
Xin
X
Reiser
Carolin
C
Fachinger
Patrick
P
Zimmermann
Arthur
A
Büchler
Markus W
MW
Di Sebastiano
Pierluigi
P
Friess
Helmut
H
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
D011498:Protein Precursors; D012333:RNA, Messenger; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C044206:preprotachykinin; D015260:Neprilysin