title: Spatial and temporal analysis of nociception-related spinal cord matrix metalloproteinase expression in a murine neuropathic pain model.
abstract: BACKGROUND
  Although the mammalian central nervous system contains numerous matrix metalloproteinases (MMPs), the significance of each MMP relative to nociception remains obscure. Working from the hypothesis that MMPs may be involved in activity-dependent reorganization during neuronal modulation, we explored the role of each MMP following neuropathological injury by establishing MMP expression profiles in a murine model for neuropathic pain.
  
  
  METHODS
  Sciatic nerves of adult male C57BL/6C mice were partially ligated, and their responses to mechanical and radiant heat stimulations were observed at 1, 3, 7, and 14 days. The expression of several nociception-related MMPs (MMP-2, MMP-9, MMP-12, MMP-17, and MMP-24) in the spinal cord was detected by immunohistochemical analysis, Western blotting, and real-time polymerase chain reaction. In addition, the potential of GM6001, a general inhibitor of MMP peritoneal administration, to modulate nociceptive pain responses in a chronic neuropathic pain model in mice was also investigated.
  
  
  RESULTS
  MMP-2, 9, 17, and 24, but not MMP-12, were expressed in the murine spinal cord. MMP-9 was constitutively expressed in neurons and microglial cells, immediately upregulated after nerve injury, and returned to baseline levels at day 3. Expression of MMP-2, MMP-17, and MMP-24 gradually increased after nerve injury. Morphologically, MMP-2-positive cells were glial-like cells. MMP-17 and MMP-24 expression was widespread in gray matter, neurons, and microglial cells, and concentrated in the marginal zone of the dorsal horn and in small capillaries. Peritoneal administration of GM6001 resulted in significantly attenuated thermal hyperalgesia and tactile allodynia induced by nerve injury.
  
  
  CONCLUSIONS
  Expression of several nociception-related MMPs was differentially regulated both temporally and spatially following nerve injury. These results suggest that neuronal remodeling requires concerted expression of particular MMPs in specific temporal and spatial patterns, which may be necessary for neuronal plasticity and/or recovery.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan, ROC.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Liou
authors.forename: Daniel Ching-Wah
authors.initials: DC
authors.lastname: Sum
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Liu
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Mao
authors.forename: Ying-Shu
authors.initials: YS
authors.lastname: Lai
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000201:enzymology*; D009473:Neuronal Plasticity; D059225:Nociception / Q000502:physiology*; D013116:Spinal Cord / Q000201:enzymology*
chemical_list: D020782:Matrix Metalloproteinases