Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis

Abstract

In order to evaluate more fully the role of neuropeptides in the pathogenesis of psoriasis, skin biopsies were obtained from 36 patients with psoriasis to identify substance P (SP), vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). Lesional and nonlesional skin was examined from these biopsies and the results compared with those from biopsies taken from patients with a variety of other inflammatory dermatoses, including lichen planus, lichen simplex chronicus, spongiotic dermatitis, and seborrheic dermatitis. Also studied was a series of nine biopsies taken from patients with no known skin disorders. We found an increase in the number of SP-positive nerve fibers within the epidermis in biopsies from lesional skin of psoriasis patients (8.4 nerves per 3-mm biopsy) compared with nonlesional psoriatic skin (2.6 nerves per 3-mm biopsy) and normal skin (2.0 nerves per 3 mm biopsy). Other inflammatory disorders also demonstrated fewer SP-positive nerves than lesional psoriatic skin; lichen planus (0 nerves per 3 mm biopsy) and lichen simplex chronicus (1.3 nerves per 3 mm biopsy). The difference in SP-positive nerve expression between lesional psoriatic skin and the group comprising nonlesional skin, normal skin, lichen planus, and lichen simplex chronicus attained statistical significance (P < 0.013). SP-positive intraepidermal nerve fibers in lesional psoriatic specimens were fewer than in spongiotic dermatitis (17.4 nerves per 3 mm biopsy). There was no significant difference in numbers of VIP- or CGRP-immunopositive intraepidermal nerve fibers between psoriatic skin and the group comprising all other material tested. However, in five patients with psoriasis, there was a marked increase in the expression of intraepidermal CGRP (up to 10.7 nerves per 3-mm biopsy) and VIP (up to 8.3 nerves per 3-mm biopsy) which was not observed in control groups. These findings suggest that neuropeptides SP, CGRP, and VIP play a role in the pathogenesis of psoriasis.

Revisiting the Koebner Phenomenon

“…31 In our earlier studies we have substantiated this hypothesis by demonstrating that the psoriasis plaques are characterized by marked proliferation of terminal cutaneous nerves in association with up-regulation of NGF-R (p75) and increased density of neuropeptergic nerve fibers expressing SP and CGRP. 18,29,32 In this study we observed a marked proliferation of NGF-R (p75)-positive nerve fibers in the transplanted psoriatic plaque compared to a few nerves in the transplanted normal human skin ( Figure 6). These observations firmly demonstrate that NGF released from the keratinocytes of psoriatic plaques is functionally active.…”

“…28 It has also been reported that keratinocytes are an important source of NGF, and topical administration of NGF significantly accelerates regeneration of nerve fibers. 26,27,29,30 Thus, in conditions with the increased epidermal expression of NGF, such as in psoriasis 16,17 it is expected that there would be increased nerve fibers and abundant expression of NGF-R in the cutaneous nerves. Up-regulation of the p75 receptor along with sprouting of terminal cutaneous nerve fibers are an unique in vivo effect of NGF.…”

Updated Neurophysiology of Itch

“…46) despite all publications regarding SP-induced itch in animals, it is still controversial whether SP plays an important role in itch induction in human skin. Increased local levels of SP and nK1R have been reported in pruritic skin diseases such as atopic dermatitis, 47) urticaria, 48) and psoriasis, 49) suggesting that SP is involved in itch induction in humans, too. However, SP-induced itch in humans seems to be at least partly mediated via histamine release from mast cells.…”

Psoriasis, a Systemic Disease Beyond the Skin, as Evidenced by Psoriatic Arthritis and Many Comorbities – Clinical Remission with a Leishmania Amastigotes Vaccine, a Serendipity Finding

“…SP can stimulate mast cells (Kawana et al, 2006;Kandere-Grzybowska et al, 2003) and contributes to inflammation (Leeman & Ferguson, 2000;O'Connor et al, 2004). SP-positive nerve fibers are denser in psoriatic lesions and have an increased number of mast cell contacts compared to normal skin (Chan et al, 1997;Al'Abadie et al, 1995). The nervous system contributes to inflammatory skin diseases.…”