NK-1 receptor gene expression is related to pain in chronic pancreatitis.
Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP. Pancreatic tissues from 31 patients (22 males, nine females; mean age 45.9+/-9.4 years) with CP were evaluated. Nine normal pancreases (five males, four females; mean age 42.9+/-9.5 years) served as controls. Quantitative PCR was used to determine the NK-1R mRNA expression levels and in situ hybridization and immunohistochemistry were used to localize expression sites of NK-1R mRNA and protein, respectively. We also analyzed whether an association exists between NK-1R mRNA expression and pain and inflammation. In CP samples, in situ hybridization and immunohistochemistry localized NK-1R mRNA expression and protein mainly in the nerves, ganglia, blood vessels, inflammatory cells and occasionally in fibroblasts. In patients with mild to moderate and strong intensity of pain, NK-1R mRNA levels were increased 14- and 30-fold over controls, respectively. There was a significant relationship between NK-1R mRNA levels and intensity of pain (r=0.46, P=0.03), NK-1R mRNA and the frequency of pain (r=0.51, P=0.04), and NK-1 mRNA and duration of pain (r=0.46, P=0.01) in CP patients, but not with the degree of tissue inflammation. NK-1R signaling may be involved in the pain syndrome of CP. The expression of NK-1R in inflammatory cells and blood vessels also points to an interaction of immunoreactive substance P nerves, inflammatory cells and blood vessels, and further supports the existence of a neuroimmune interaction that probably influences the pain syndrome and chronic inflammatory changes so characteristic of CP.
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland Institute of Pathology, University of Bern, Inselspital, Bern, Switzerland.
Shailesh V
SV
Shrikhande
Helmut
H
Friess
Fabio F
FF
di Mola
Adrien
A
Tempia-Caliera
José R
JR
Conejo Garcia
Zhaowen
Z
Zhu
Arthur
A
Zimmermann
Markus W
MW
Büchler
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D015213:Neuroimmunomodulation; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010179:Pancreas / Q000737:chemistry / Q000294:innervation / Q000503:physiopathology; D010195:Pancreatitis / Q000150:complications / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1