Plasminogen repairs abnormal pain perception through improving sensory function recovery and regeneration of peripheral small nerve fiber in db/db mice

Painful diabetic peripheral neuropathy (PDPN) is a devastating complication of diabetes and severely threatens the health of humankind. The plasminogen activator system and plasminogen (Plg) have multiple functional roles in tissue regeneration and extracellular matrix remodeling, which suggests that Plg may have a potentially pivotal role in anti-PDPN. In the present study, we explore whether an increased level of circulating Plg has positive effect on repairing abnormal pain perception in diabetic mice model. Our data demonstrated that additional Plg not only helps healing pain allodynia or hyperalgesia on the mice at the age of 8 weeks old in early PDPN, but more important, also has positive effects of regaining normal pain perception from hypoalgesia on the mice at ages of 14-15 or 24-25 weeks in advanced PDPN. Furthermore, our data also reveal a possible mechanism for Plgs contribution to rebuilding normal pain perception among db/db mice by promoting axonal myelination and regeneration of small nerve fiber in peripheral nervous system. Therefore, our data suggest that Plg show promise to become a drug candidate for treating diabetic peripheral neuropathic pain.