RGD Reference Report - Spinal matrix metalloproteinase 3 mediates inflammatory hyperalgesia via a tumor necrosis factor-dependent mechanism. - Rat Genome Database

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Spinal matrix metalloproteinase 3 mediates inflammatory hyperalgesia via a tumor necrosis factor-dependent mechanism.

Authors: Christianson, CA  Fitzsimmons, BL  Shim, JH  Agrawal, A  Cohen, SM  Hua, XY  Yaksh, TL 
Citation: Christianson CA, etal., Neuroscience. 2012 Jan 3;200:199-210. doi: 10.1016/j.neuroscience.2011.10.019. Epub 2011 Oct 20.
RGD ID: 8693664
Pubmed: PMID:22056600   (View Abstract at PubMed)
PMCID: PMC3346277   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuroscience.2011.10.019   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia  ISOMmp3 (Rattus norvegicus)8693664; 8693664 RGD 
Hyperalgesia  IMP 8693664 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp3  (matrix metallopeptidase 3)

Genes (Mus musculus)
Mmp3  (matrix metallopeptidase 3)

Genes (Homo sapiens)
MMP3  (matrix metallopeptidase 3)


Additional Information