Changes in cutaneous sensory nerve fibers induced by skin-scratching in mice

Skin-scratching behavior, a common response observed in patients with pruritus, is supposed to promote the sprouting of cutaneous sensory nerve fibers. Thus, it sometimes exacerbates the original lesions. However, the precise changes that develop in cutaneous sensory nerve fibers after skin-scratching have not yet been elucidated.

To investigate how and what kinds of cutaneous sensory nerve fibers increase and how nerve growth factor (NGF) and its receptors change after skin-scratching.

After scratching the dorsal skin of anesthetized ICR mice, change in cutaneous nerve fibers was detected by immunofluorescence for protein gene product 9.5 (PGP9.5), substance P (SP) and/or calcitonin gene-related peptide (CGRP). To investigate the involvement of NGF signaling, the production of NGF and the expression of its receptors were examined using ELISA and/or immunofluorescence, respectively.

Skin-scratching dramatically induced the sprouting of cutaneous nerve fibers. Both dermal and epidermal nerve fibers began to increase and reached a peak at days 3-7. At the same time, nerve fibers containing SP or CGRP increased significantly. NGF in the scratched skin increased immediately and reached a peak at days 1-3. The expression of NGF receptors, such as phosphorylated trk A and p75, on nerve fibers was remarkably upregulated within 2 days.

Skin-scratching induced the sprouting of cutaneous sensory nerve fibers in the skin within several days, thus possibly leading to enhanced neurogenic inflammation. Analyses of the expression of NGF and its receptors suggest that NGF signaling may be, at least in part, involved in these changes.