Novel Animal Models of Acute and Chronic Cancer Pain: A Pivotal Role for PAR2

• DOI: 10.1523/jneurosci.2399-12.2012
• Publication Date: 2012-10-10T18:54:32Z
• Authors: David K. Lam; Dongmin Dang; Jianan Zhang; John C. Dolan; Brian L. Schmidt
• Keywords: Mice, Knockout; 0303 health sciences; Mice, Transgenic; Acute Pain; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Head and Neck Neoplasms; Cell Line, Tumor; Animals; Humans; Receptor, PAR-2; Female; Chronic Pain

Targeted therapy to prevent the progression from acute chronic pain in cancer patients remains elusive. We developed three novel models mice that together recapitulate anatomical, temporal, and functional characteristics of head neck humans. Using pharmacologic genetic approaches these models, we identified interaction between protease-activated receptor 2 (PAR2) serine proteases be central importance. show such as trypsin induce a PAR2-dependent manner. Chronic is associated with elevated microenvironment PAR2 upregulation peripheral nerves. Serine protease inhibition greatly reduces severity persistent wild-type mice, but most strikingly, development prevented PAR2-deficient mice. Our results demonstrate direct role for suggest may favor maintenance pain. Targeting PAR2-serine promising approach treatment prevention