Evidence of a role for NK₁ and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear

1. The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. 2. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK₁ receptor knockout mice (-/-). Blood flow was assessed by laser Doppler flowmetry and oedema formation by ¹²⁵I-albumin accumulation. 3. Capsaicin induced significant increases in blood flow (0.2-200 μg in 20 μl) and oedema (2-200 μg in 20 μl). The oedema response was absent in NK₁-/- mice and NK₁ +/+ mice treated with the selective NK₁ receptor antagonist SR140333 (480 nmol kg^-1) as expected. Furthermore, the capsaicin-evoked increase in blood flow was significantly potentiated in the knockout mice (203% of wild-type response, P < 0.05) and wild-type mice treated with SR140333 (201%, P < 0.05). 4. The CGRP receptor antagonist CGRP_8-37 (400 nmol kg^-1) had no effect on capsaicin-induced blood flow in NK₁ +/+ mice but abolished the increased blood flow to capsaicin in NK₁-/-, and NK₁ +/+wild-type mice pre-treated with SR140333. 5. The results indicate that neurogenic vasodilatation can be measured in the mouse ear. The capsaicin-induced increased blood flow involves activation of, and possible interactions between, both NK₁ and CGRP₁ receptors.