Open AccessRole of Matrix Metalloproteinases in Myelin Abnormalities and Mechanical Allodynia in Rodents with Diabetic Neuropathy
Author(s) -
Xiaheng Deng,
Pingchuan Ma,
Mingzheng Wu,
HuaBao Liao,
XueJun Song
Publication year - 2021
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2021.0126
Subject(s) - matrix metalloproteinase , medicine , diabetic neuropathy , allodynia , diabetes mellitus , myelin , pharmacology , endocrinology , hyperalgesia , central nervous system , nociception , receptor
The treatment of diabetic neuropathic pain (DNP) is a major clinical challenge. The underlying mechanisms of diabetic neuropathy remain unclear, and treatment approaches are limited. Here, we report that the gelatinases MMP-9 and MMP-2 play a critical role in axonal demyelination and DNP in rodents. MMP-9 may contribute to streptozotocin (STZ)-induced DNP via inducing axonal demyelination and spinal central sensitization, while MMP-2 may serve as a negative regulator. In STZ-induced DNP rats, the activity of MMP-9 was increased, while MMP-2 was decreased in the dorsal root ganglion and spinal cord. Spinal inhibition of MMP-9, but not MMP-2, greatly suppressed the behavioral and neurochemical signs of DNP, while administration of MMP-2 alleviated mechanical allodynia. In mice, STZ treatment resulted in axonal demyelination in the peripheral sciatic nerves and spinal dorsal horn, in addition to mechanical allodynia. These neuropathic alterations were significantly reduced in MMP-9 -/- mice. Finally, systematic administration of α-lipoic acid significantly suppressed STZ-induced mechanical allodynia by inhibiting MMP-9 and rescuing MMP-2 activity. These findings support a new mechanism underlying the pathogenesis of diabetic neuropathy and suggest a potential target for DNP treatment. Gelatinases MMP-9 and MMP-2 play a critical role in the pathogenesis of diabetic neuropathy and may serve as a potential treatment target. MMP-9/2 underlies the mechanism of α-lipoic acid in diabetic neuropathy, providing a potential target for the development of novel analgesic and anti-inflammatory drugs.