Proteinase-activated receptor-2 and hyperalgesia: A novel pain pathway

N. Vergnolle, N. W. Bunnett, K. A. Sharkey, V. Brussee, S. J. Compton, E. F. Grady, G. Cirino, N. Gerard, A. I. Basbaum, P. Andrade-Gordon, M. D. Hollenberg, J. L. Wallace

Research output: Contribution to journalArticle

Abstract

Using a combined pharmacological and gene-deletion approach, we have delineated a novel mechanism of neurokinin-1 (NK-1) receptor-dependent hyperalgesia induced by proteinase-activated receptor-2 (PAR2), a G-protein-coupled receptor expressed on nociceptive primary afferent neurons. Injections into the paw of sub-inflammatory doses of PAR2 agonists in rats and mice induced a prolonged thermal and mechanical hyperalgesia and elevated spinal Fos protein expression. This hyperalgesia was markedly diminished or absent in mice lacking the NK-1 receptor, preprotachykinin-A or PAR2 genes, or in rats treated with a centrally acting cyclooxygenase inhibitor or treated by spinal cord injection of NK-1 antagonists. Here we identify a previously unrecognized nociceptive pathway with important therapeutic implications, and our results point to a direct role for proteinases and their receptors in pain transmission.

Original languageEnglish (US)
Pages (from-to)821-826
Number of pages6
JournalNature Medicine
Volume7
Issue number7
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Vergnolle, N., Bunnett, N. W., Sharkey, K. A., Brussee, V., Compton, S. J., Grady, E. F., Cirino, G., Gerard, N., Basbaum, A. I., Andrade-Gordon, P., Hollenberg, M. D., & Wallace, J. L. (2001). Proteinase-activated receptor-2 and hyperalgesia: A novel pain pathway. Nature Medicine, 7(7), 821-826. https://doi.org/10.1038/89945