Local keratinocyte-nociceptor interactions enhance obesity-mediated small fiber neuropathy via NGF-TrkA-PI3K signaling axis.

ABSTRACT: The pathology of diabetic small fiber neuropathy, characterized by neuropathic pain and axon degeneration, 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 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. Further mechanistic analysis identified keratinocytes as a major source of nerve growth fac

SUBMITTER: Koui Y 

PROVIDER: S-EPMC11452191 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature