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 car 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 I-125-albumin accumulation. 3 Capsaicin induced significant increases in blood flow (0.2-200 mug in 20 mul) and oedema (2-200 mug in 20 mul). 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 car. The capsaicin-induced increased blood flow involves activation of, and possible interactions between, both NK1 and CGRP(1) receptors.