A transient unresponsive state of self-scratching behaviour is induced in mice by skin-scratching stimulation.

When mice were scratched with brushes on their dorsal skins, they began to scratch themselves with their hind paws. Thus, self-scratching behaviour was induced in mice in response to skin-scratching stimulation. If the second skin-scratching stimulation was given within a few days, the induction of the second self-scratching behaviour was significantly suppressed compared with the first one. Thereafter, mice gradually recovered from this unresponsive state within a week. Thus, a transient unresponsive state of self-scratching behaviour is induced by skin-scratching stimulation. Pretreatment with a tachykinin receptor NK-1R antagonist L-703606 or capsaicin significantly suppressed self-scratching behaviour, while pretreatment with a neutral endopeptidase inhibitor phosphoramidon significantly enhanced it. Pretreatment with a calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) did not affect the following self-scratching behaviour. From these results, it is suggested that substance P (SP) signalling through its receptor NK-1R at least in part mediates the induction of self-scratching behaviour. After skin-scratching stimulation, immunoreactivity of SP both in the peripheral nerve fibres and in the dorsal root ganglion (DRG) neurons was significantly decreased and was well-correlated with suppression of self-scratching behaviour. From these findings, it is suggested that the induction of unresponsive states of self-scratching behaviour may be at least in part caused by the depleted states of SP in peripheral nerve fibres and/or in DRG neurons. The induction of a transient unresponsive state after skin-scratching may possibly happen also in patients with pruritus. Thus, further studies to elucidate the precise mechanisms are required.