From the Perspective of the Peripheral Sensory Nervous System: The Role of Vitamin D in Neurogenic Inflammatory Skin Disorders

Vitamin D (VD) is a secosteroid hormone with critical physiologic roles in calcium homeostasis and bone mineralization. Recently, studies have uncovered VD's broader effects on immune system and nervous system function. VD receptors (VDRs) and enzymes responsible for the metabolism of VD have been discovered in dorsal root ganglion (DRG) neurons and nociceptive sensory neurons, implicating VD as a potential regulator of neurogenic inflammation. Neurogenic inflammation is a phenomenon in which sensory nerve fibers in the peripheral nervous system (PNS) are activated and release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), resulting in vasodilation, cytokine production, and immune cell infiltration. This process has been shown to drive chronic inflammatory skin disorders, including atopic dermatitis (AD) and psoriasis. VD has been recognized as a key factor in the pathogenesis and management of both conditions; however, the mechanism underlying its clinical benefits remains unclear. Emerging evidence has shown VD to influence CGRP signaling, interleukin-6 (IL-6) production, and TRPV1 channel activity-pathways that are integral to nociception and pruritus, as well as the Th17- and Th2-driven inflammation seen in psoriasis and AD, respectively. Thus, this review provides an overview of VD's possible mechanistic role in neurogenic skin inflammation and the implications of these pathways for identifying new therapeutic targets for psoriasis and AD.