MHI Seminar Series presents Yosuke Mukoyama, PhD, Senior Investigator, Lab Stem Cell & Neurovascular Biology, Cell & Developmental Biology Center, NHLBI/NIH

Summary of Seminar:  The pathology of diabetic small fiber neuropathy, characterized by neuropathic pain, axon degeneration and abnormal microvasculature, develops locally within the skin during the stages of obesity and pre-diabetes. However, the initiation and progression of morphological and functional abnormalities in skin sensory nerves and vasculature remains elusive. To address this, we utilized ear skin from mice with diet-induced obesity (DIO), the mouse models for obesity and pre-type 2 diabetes. We evaluated pain-associated wiping behavior and conducted ex vivo live Ca2+ imaging of the DIO ear skin to detect sensory hypersensitivity. Our findings reveal sensory hypersensitivity in skin nociceptive axons followed by axon degeneration. The data also indicate the potential involvement of increased vascular permeability within the DIO skin, facilitating the diffusion of circulating insulin from dermal capillaries into the non-capillary epidermis. Such elevated local insulin levels enhance NGF expression in keratinocytes, which locally sensitizes nociceptors through NGF-TrkA signaling. Targeting these local neuro-vascular and neuro-keratinocyte interactions for managing neuropathic pain will be discussed.

UNC Lineberger Comprehensive Cancer Center, Pagano Conference Room (LCCC 00-002)
450 West Dr.
Chapel Hill, North Carolina 27599
United States
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