Skin Biopsy: From a Diagnostic Tool to a Powerful Asset for Basic and Translational Research in Peripheral Neuropathic Pain

Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. PDN is characterized by small-fiber degeneration, which can progress to complete loss of cutaneous innervation and is accompanied by neuropathic pain. Uncovering the mechanisms underlying the degeneration of cutaneous nerves in PDN remains a major challenge to finding effective and disease-modifying therapy. Sensory nerve afferents normally extend into the epidermis in close communication with keratinocytes but degenerate in diabetic skin Dr. Menichella will discuss how an unbiased single-cell transcriptional approach to mouse skin and of skin biopsy from patients is a powerful tool in the lab and in the clinics to explore the mechanisms by which keratinocytes communicate with cutaneous afferents and how this communication impacts axonal degeneration underlying neuropathic pain in PDN. Dr. Menichella will demonstrate that activation of basal keratinocyte Gq-linked GPCRs influences neuronal and keratinocyte function to impact nerve regeneration and integrity and prevent neuropathic pain. D Menichella will discuss how an improved understanding of neuron to keratinocyte communication in diabetic skin could translate into new topical interventions, including based on GPCR agonism or antagonism, which could meet the unmet need for therapy for both small-fiber degeneration and neuropathic pain in diabetes.