| Literature DB >> 28783046 |
Loren J Martin1,2, Shad B Smith3, Arkady Khoutorsky4, Claire A Magnussen5, Alexander Samoshkin6, Robert E Sorge1, Chulmin Cho2, Noosha Yosefpour5, Sivaani Sivaselvachandran2, Sarasa Tohyama2, Tiffany Cole7, Thang M Khuong7, Ellen Mir3, Dustin G Gibson3, Jeffrey S Wieskopf1, Susana G Sotocinal1, Jean Sebastien Austin1, Carolina B Meloto6, Joseph H Gitt3, Christos Gkogkas4, Nahum Sonenberg4, Joel D Greenspan8, Roger B Fillingim9, Richard Ohrbach10, Gary D Slade11, Charles Knott12, Ronald Dubner8, Andrea G Nackley3, Alfredo Ribeiro-da-Silva5, G Gregory Neely7, William Maixner3, Dmitri V Zaykin13, Jeffrey S Mogil1, Luda Diatchenko6.
Abstract
The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions.Entities:
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Year: 2017 PMID： 28783046 PMCID： PMC5669538 DOI： 10.1172/JCI87406
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808