Spinal matrix metalloproteinase 8 regulates pain after peripheral trauma

Abstract

Maral Tajerian,1 J David Clark2–41Department of Biology, Queens College, City University of New York, Queens, NY 11367, USA; 2Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA; 3Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA 94305, USA; 4Palo Alto Veterans Institute for Research, Palo Alto, CA 94304, USAAbstract: It is well documented that pain chronification requires a host of plastic mechanisms at the spinal cord (SC) level, including alterations in neuronal and glial structure and function. Such cellular plasticity necessitates the existence of a plastic extracellular matrix (ECM). Here, we describe a key role for ECM remodeling in the regulation of chronic pain following peripheral injury. Three weeks following tibia fracture in mice, we show increased levels of MMP8 in the SC. Furthermore, we show that the pharmacological or genetic downregulation of MMP8 ameliorates the pain phenotype observed after injury. These results delineate an extracellular mechanism for pain chronification, thereby improving our mechanistic understanding of pain and providing novel therapeutic venues that go beyond targeting individual cell types.Keywords: spinal cord, chronic pain, matrix metalloproteinase 8, mouse model, mechanical allodynia, shRN