The proteinase-activated receptor 2 is involved in nociception.
The proteinase-activated receptor 2 is expressed on a subset of primary afferent neurons and may participate in the neurogenic component of inflammation. We hypothesized that this receptor may also play a role in neuronal sensitization and contribute to the pathogenesis of pain in inflammatory conditions such as pancreatitis. Using a specific proteinase-activated receptor 2 activating peptide, we found evidence of such sensitization in vitro in the form of enhanced capsaicin- and KCl-evoked release of calcitonin gene-related peptide, a marker for nociceptive signaling. We then demonstrated that injection of the proteinase-activated receptor 2 activating peptide into the pancreatic duct can activate and sensitize pancreas-specific afferent neurons in vivo, as measured by Fos expression in the dorsal horn of the spinal cord. These observations suggest that proteinase-activated receptor 2 contributes to nociceptive signaling and may provide a novel link between inflammation and pain.
Hoogerwerf
W A
WA
Enteric Neuromuscular Disorders and Pain Laboratory, University of Texas Medical Branch, Galveston, Texas 77555-0764, USA.
Zou
L
L
Shenoy
M
M
Sun
D
D
Micci
M A
MA
Lee-Hellmich
H
H
Xiao
S Y
SY
Winston
J H
JH
Pasricha
P J
PJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin; D002478:Cells, Cultured; D004333:Drug Administration Routes; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D010183:Pancreatic Ducts / Q000187:drug effects; D020671:Posterior Horn Cells / Q000378:metabolism; D011189:Potassium Chloride; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000008:administration & dosage / Q000819:agonists / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D011189:Potassium Chloride; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin