Regulation and Function of Matrix Metalloproteinases in Nervous System Injury and Neuropathic Pain

Abstract

The balance between expression of matrix metalloproteases (MMPs) and their endogenous tissue inhibitors (TIMPs) has important implications for the healthy nervous system as well as pathogenesis and recovery in disease or injury. The functional consequences of MMP activity depend on the cellular localization, tissue distribution, and temporal pattern of MMP expression. MMP expression and activity is controlled by intracellular and extracellular signaling molecules, cell surface receptor activity, transcription factors, proteolytic activation of inactive MMP pro-forms, and inhibition by TIMPs. Evidence that MMPs are not only effectors of tissue damage, but may be operational in repair mechanisms has indicated the need to re-examine the role of MMPs after acute processes such as stroke and traumatic spinal cord injury, as well as in chronic conditions such as neuropathic pain. Here we review recent evidence for a beneficial and harmful role for MMPs following central and peripheral nerve injury, as well as their involvement in neuropathic pain following such injury. Finally, therapeutic potential of modifying MMP activity is discussed and considerations for future directions. doi: 10.5214/ans.0972.7531.2008.150402 Competing interests: None. Source of Funding: None Received Date: 15 Aug 2008 Revised Date: 09 Sept 2008 Accepted Date: 23 Sept 2008