B6.2 NERVES, NEUROPEPTIDES, AND THE HUMAN ANAGEN HAIR FOLLICLE

Maria Hordinsky, MD, Marna Ericson, PhD

Department of Dermatology, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Hair loss patients may describe “pain” when their hair is combed or brushed or when the wind blows through their hair. Patients with alopecia areata may report “pain” or “itch” with hair loss or hair regrowth. The etiology of these symptoms is not well understood. To examine nerve and neuropeptide (calcitonin gene related peptide and substance P expression) in such patients, we collected four-mm scalp punch biopsy specimens from normal control subjects, two patients with extensive alopecia areata before and after application of capsaicin for 21 days and patients with painful scalps. Specimens were processed for routine histopathological examination and were multi-labeled with antibodies to (1) pan-neuronal protein gene product 9.5 (PGP 9.5) and Cyanine 3.18, Substance P or CGRP and Cyanine 5.18 as well as the vascular marker UEA I agglutinin conjugated to fluorescein. In-focus images of well-defined optical sections (0.5-1.0 microns) were captured by laser scanning confocal microscopy. Analysis of normal human scalp specimens was similar to previous descriptions of the perifollicular nerve network. Analysis of 21 day scalp biopsy AA samples compared to baseline revealed (1) a qualitative decrease in the number of nerves staining with PGP 9.5 and SP in the epidermis, (2) small extra-neuronal globules staining with antibody to SP and (3) abundance of SP expression in the stockade region of the miniaturized follicle. These results indicate cutaneous innervation is altered in alopecia areata. Analysis of scalp biopsies taken from patients with “symptomatic scalp” revealed several substance P staining globules within the vasculature suggesting the symptoms these patients experience may be more related to enhanced expression of SP on lymphocytes, macrophages, or eosinophils, all of which have receptors for SP, rather than to alterations in the peripheral nervous system.