Rho GTPase-activating protein DLC2 deficiency in mice leads to more severe painful diabetic neuropathy

Abstract

DLC2, a Rho GTPase-activating protein with specific activity for RhoA, has been shown to play a role in pain response. Mice deficient for this protein (DLC2 KO) are hyperalgesic compared to wild type in acute pain tests, showing higher response to noxious thermal and inflammatory stimuli, while also showing an increase in RhoA activity in peripheral nerves. Because of the increased acute pain response in DLC2 KO mice, and since RhoA is known to be involved in the development and maintenance of diabetic complications, we used them to study chronic pain in a model of diabetic neuropathy. Wild type (DLC2 WT) and DLC2 KO mice were subjected to multiple low dose streptozotocin (MLDS) treatment to induce diabetes. After 8 weeks, their pain response was tested. From the hot plate test, diabetic DLC2 ...