Changes of immunoreactive substance P level in mouse ear treated with capsaicin

Topical application of capsaicin, the pungent component of red peppers, to the mouse ear causes acute inflammation by the activation of tachykinin NK1 receptors. We examined the change of immunoreactive substance P (iSP) levels in the ear tissue after topical application of capsaicin (250μg/ear). The edema response to capsaicin reached a maximum at 30min and then was abolished at up to 24h after application. The iSP level in the ear tissue fell to 24% of the control value during the first 15min and was significantly reduced by 55% at 24h after application. This decrease in iSP level by capsaicin was observed for up to 28 days, but there was no difference in the iSP level between control and capsaicin-treated ears at day 48. Phosphoramidon (0.1mg/kg, i.v.), an endopeptidase inhibitor, not only enhanced edema response but also prevented the decrease of iSP levels by capsaicin. Immunohistochemical study showed that SP is localized in sensory nerves and mast cells in normal ear. SP-immunoreactivity in sensory nerves, but not mast cells, in ears treated with capsaicin was much weaker than that in untreated ears at 24h after application. These results indicate that SP is released immediately from sensory nerve endings by application of capsaicin and is cleaved by endogenous endopeptidases in the mouse ear. Furthermore, it appears that recovery of SP in the ear tissue demands for more than a month after topical application of capsaicin in adult mice.