title: Matrix metalloproteinases: potential therapeutic target for diabetic neuropathic pain.
abstract: BACKGROUND
  MMPs are zinc-dependent endopeptidases that play a key role in the remodeling of extracellular matrix (ECM). Various pathogenic mediators trigger abnormal MMP activity that leads to ECM abnormality. Hyperglycemia is one of the strong stimuli among oxidative stress and inflammation that upregulate MMP expression in the central and peripheral nervous system. MMP-mediated ECM abnormality hypersensitizes peripheral as well as central nerves that precipitate neuropathic pain in diabetic patients.
  
  
  METHODS
  Molecular mechanisms associated with MMP-mediated diabetic neuropathic pain have been discussed. Various endogenous, natural and synthetic MMP inhibitors are also explored.
  
  
  CONCLUSIONS
  In diabetes, hyperglycemia activates MMPs that along with the other pathogenic mediators cause neuronal injury and precipitates neuropathic pain. Thus, MMPs play a crucial role in the development of neuropathic pain among diabetics. However, MMPs are not only responsible for deleterious ECM abnormalities but are also required for beneficial remodeling of ECM under normal physiological conditions. Therefore, highly selective and specific inhibitors must be designed and explored for their clinical potential for treatment/prevention of diabetic neuropathic pain.
authors.affiliation: Panjab University, University Institute of Pharmaceutical Sciences, Pharmacology Research Laboratory, UGC Centre of Advanced Study , Chandigarh - 160 014 , India +91 9915173064 ; +91 172 2534101 ; anurag_pu@yahoo.com.
authors.forename: Anurag
authors.initials: A
authors.lastname: Kuhad
authors.forename: Pratishtha
authors.initials: P
authors.lastname: Singh
authors.forename: Kanwaljit
authors.initials: K
authors.lastname: Chopra
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases
keywords: MMP; astrocytes; cytokines; diabetic neuropathy; extracellular matrix; microglia; oxidative stress; tissue inhibitor of metalloproteinase