Capsaicin-Mediated Neurogenic Vasodilatation in Neurokinin-1, NK1, Receptor Knockout Mice

Capsaicin induces tachykinin NK1 receptor-dependent neurogenic oedema in the mouse ear and this model has been used to determine the absence of NK1 receptors in NK1 knockout (NK1-/-) mice[1]. We have now simultaneously measured neurogenic vasodilatation and oedema in the ear. Wild-type and NK1-/Sv129+C57BL/6 mice were used in this study. Anaesthesia (urethane, 25% w/v; 100ml/10g) was induced. Oedema was assessed by the accumulation of Ialbumin, and blood flow by laser Doppler flowmetry. Responses were measured for 1 h after topical application of capsaicin to one ear and vehicle to the contralateral ear. Capsaicin induced oedema in wild-type Sv129+C57BL/6 mice (p < 0.001), but not in NK1-/mice, as expected[2]. However, neurogenic vasodilatation (p < 0.05) was observed in both wild-type and NK1-/mice, and remained in wild-type mice in the presence of the NK1 antagonist SR140333 (480 nmol/kg). Interestingly, increased blood flow in the NK1-/mice was significantly (p < 0.05) greater than that in the wild-type mice. It was substantially blocked in NK1-/mice pretreated with the CGRP antagonist CGRP8-37 (400nmol/kg), or wild-type mice treated with both SR140333 and CGRP8-37, but not in wild-type mice treated with CGRP8-37 alone. The results suggest that neurogenic vasodilatation is a consequence of CGRP and NK1 receptor mediated responses in the mouse. They also indicate that some form of interaction between functional CGRP and NK1 receptors may occur. A.D. Grant is supported by a BHF studentship.