Matrix metalloproteinases: potential therapeutic target for diabetic neuropathic pain

Abstract

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.

Serum Level of Metalloproteinase-2 but not Metalloproteinase-9 Rises in Patients With Failed Back Surgery Syndrome After Spinal Cord Stimulation

“…NP is a chronic condition, the result of diverse, complex, and sometimes opposing processes, both regenerative and destructive . MMPs are not only responsible for deleterious effects on the extracellular matrix (ECM) but are also required for beneficial remodeling of the ECM under normal physiological conditions . The elevated level of MMP‐2 in patients with FBSS before implantation and further increase after SCS implantation suggests possible role of MMP‐2 in alleviation of NP.…”

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling

“…Increased levels of both MMP-2 and MMP-9 have been implicated in the generation and maintenance of neuropathic pain in diabetes. 22,23 Currently, six tenascin (TN) glycoprotein family have been identified. Of those, TN-C and TN-R are the best characterized members and have been implicated in the early development of central and peripheral nervous systems.…”

In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain

“…Isoorientin also reduced the MMP-9 expression as well as overexpressed astrocytes and microglia in CCI operated mice [131]. MMP-9 is required for the activation of glial cell via activating pro-inflammatory cytokines [106,149]. In another study, morin treatment improved sciatic functional index (SFI) but was unable to completely recover to the normal SFI.…”

“…Matrix metalloprotease 9 (MMP-9) plays an important role in neuropathic pain and is associated with neuroinflammation and oxidative stress [105][106][107]. MMP-9 is activated by ROS produced at the site of injury.…”