SPINAL MATRIX METALLOPROTEINASE 3 MEDIATES INFLAMMATORY HYPERALGESIA VIA A TUMOR NECROSIS FACTOR-DEPENDENT MECHANISM
- Title
- SPINAL MATRIX METALLOPROTEINASE 3 MEDIATES INFLAMMATORY HYPERALGESIA VIA A TUMOR NECROSIS FACTOR-DEPENDENT MECHANISM
- Author
- 심재항
- Keywords
- matrix metalloproteinase 3; tumor necrosis factor; pain; inflammation; hyperalgesia; allodynia
- Issue Date
- 2012-01
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
- Citation
- NEUROSCIENCE, 권: 200, 페이지: 199-210
- Abstract
- Matrix metalloproteinases (MMPs) have been implicated in the modulation of synaptic plasticity, glial activation, and long-term potentiation in the CNS. Here we demonstrate for the first time a mechanism for the regulation of nociceptive processing by spinal MMP-3 during peripheral inflammation. We first determined by western blotting that the catalytic (active) form of MMP-3 (cMMP-3) is increased in lumbar spinal cord following peripheral inflammation in rats. The peripheral inflammation-induced thermal hyperalgesia and tactile hypersensitivity was transiently (2-3 h) attenuated by intrathecal (IT) pretreatment with either an MMP-3 inhibitor (NNGH), or a broad spectrum MMP inhibitor (GM6001). In addition, IT delivery of cMMP-3 evoked hypersensitivity, whereas the pro (enzymatically inactive) form of MMP-3 did not. This suggests a pro-algesic effect of spinal MMP-3 mediated by an enzymatic mechanism. This cMMP-3-induced hypersensitivity is concurrent with increased tumor necrosis factor (TNF) in the spinal cord. The hypersensitivity behavior is prevented by intrathecal etanercept (TNF blockade). Treatment with cMMP-3 resulted in an increase in TNF release from spinal primary microglial, but not astrocyte cultures. These findings thus present direct evidence implicating MMP-3 in the coordination of spinal nociceptive processing via a spinal TNF-dependent mechanism. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
- URI
- https://www.sciencedirect.com/science/article/abs/pii/S0306452211011936
- ISSN
- 0306-4522
- DOI
- 10.1016/j.neuroscience.2011.10.019
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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