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

被引:384
作者
Vergnolle, N
Bunnett, NW
Sharkey, KA
Brussee, V
Compton, SJ
Grady, EF
Cirino, G
Gerard, N
Basbaum, AI
Andrade-Gordon, P
Hollenberg, MD
Wallace, JL [1 ]
机构
[1] Univ Calgary, Dept Pharmacol & Therapeut, Calgary, AB, Canada
[2] Univ Calgary, Dept Physiol & Biophys, Calgary, AB, Canada
[3] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada
[4] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[6] Univ Naples Federico II, Dept Expt Pharmacol, Naples, Italy
[7] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm, Boston, MA 02215 USA
[8] Harvard Univ, Sch Med, Boston, MA USA
[9] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA
[10] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[11] RW Johnson Pharmaceut Res Inst, Spring House, PA 19477 USA
关键词
D O I
10.1038/89945
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:821 / 826
页数:6
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