Lack of a significant effect of deletion of the tachykinin neurokinin-1 receptor on wound healing in mouse skin

The tachykinin neurokinin-1 (NK₁) receptor mediates the vasoactive effects of substance P and related members of the tachykinin family. Substance P acts via the NK₁ receptor to mediate increased microvascular permeability leading to oedema formation as confirmed in NK₁ receptor knockout mice. In addition there is evidence that neuropeptides such as substance P can have a modulatory effect on the wound-healing process. In this study male and female wild-type and NK₁ knockout mice were investigated for their comparative ability to induce acute oedema formation in response to topical application of capsaicin, as measured by the extravasation of intravenous radiolabelled-albumin, and wound healing in response to a cut, as measured by area of wound over the following days. Significant (P < 0.001) oedema, approximately three-fold over basal, was induced by capsaicin in both male and female wild-type mice, an indicator of a similar responsiveness irrespective of sex. However, as expected, the oedema was not observed in the knockout mice. Wounding was achieved through a 1-cm full-thickness cut into the interscapular area of dorsal skin. Wound healing was then followed in two different protocols. The wound was left to heal naturally over 14 days in the first protocol and no significant changes in healing were observed in wild-type compared to knockout. In the second protocol, the skin was sutured open for the first 48 h, to prevent the elasticity of the skin from initiating a natural healing process through flap formation. This caused a significant increase in the area of the wound. Despite this, wounds in both wild-type and knockout mice healed in an identical manner that was complete after 17 days. In conclusion, it is shown that deletion of a functional NK₁ receptor has little effect on wound healing in response to a simple cut in mouse skin.