A "brain-skin" connection has been long been observed between chronic stress and chronic inflammatory skin disease including urticaria, psoriasis, atopic dermatitis, and prurigo nodularis. The relationship appears to be bidirectional. Chronic psychological stress has been shown to sustain hyperactivity of the sympathetic branch of the autonomic nervous system. Chronic stress is proinflammatory and in the context of several dermatologic disorders may be associated with an increase in dermal nerve fiber density, mast cells, nerve growth factor and calcitonin-gene-related peptide (CGRP). Furthermore, CGRP elicits a T2-polarized T-cell response that is a hallmark of chronic pruritic conditions such as atopic dermatitis and prurigo nodularis. This T2 response contributes directly to acute pruritus as well as the sensitization of cutaneous sensory neurons that are critical for chronic pruritus. Prurigo nodularis is a debilitating skin disorder featuring prominent nerve structural, neuropeptide, and T2 cytokine aberrations that is a model deserving of future study.