Introduction: 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.
Areas covered: Molecular mechanisms associated with MMP-mediated diabetic neuropathic pain have been discussed. Various endogenous, natural and synthetic MMP inhibitors are also explored.
Expert opinion: 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.
Keywords: MMP; astrocytes; cytokines; diabetic neuropathy; extracellular matrix; microglia; oxidative stress; tissue inhibitor of metalloproteinase.