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The Journal of Neuroscience, November 15, 2001, 21(22):9036-9042

The Proteinase-Activated Receptor 2 Is Involved in Nociception

W. A. Hoogerwerf¹, L. Zou², M. Shenoy¹, D. Sun¹, M. A. Micci¹, H. Lee-Hellmich¹, S. Y. Xiao², J. H. Winston¹, and P. J. Pasricha¹

¹ Enteric Neuromuscular Disorders and Pain Laboratory, Division of Gastroenterology and Hepatology, and ² Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0764

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.

Key words: proteinase-activated receptor 2; dorsal root ganglia; nociception; pancreas; Fos; neuronal sensitization

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21229036-07$05.00/0

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