Mustard oil induces a transient receptor potential vanilloid 1 receptor-independent neurogenic inflammation and a non-neurogenic cellular inflammatory component in mice.

摘要

A neurogenic component has been suggested to play a pivotal role in a range of inflammatory/immune diseases. Mustard oil (allyl-isothiocyanate) has been used in studies of inflammation to mediate neurogenic vasodilatation and oedema in rodent skin. The aim of the present study was to analyse mustard oil-induced oedema and neutrophil accumulation in the mouse ear focussing on the roles of neurokinin 1 (NK(1)) and vanilloid (TRPV1) receptors using normal (BALB/c, C57BL/6) as well as NK(1) and TRPV1 receptor knockout mice. A single or double treatment of 1% mustard oil on the BALB/c mouse ear induced ear oedema with responses diminished by 6 h. However a 25-30% increase in ear thickness was maintained by the hourly reapplication of mustard oil. Desensitisation of sensory nerves with capsaicin, or the NK(1) receptor antagonist SR140333, inhibited oedema but only in the first 3 h. Neutrophil accumulation in response to mustard oil was inhibited neither by SR140333 nor capsaicin pre-treatment. An activating dose of capsaicin (2.5%) induced a large oedema in C57BL/6 wild-type mice that was minimal in TRPV1 receptor knockout mice. By comparison, mustard oil generated ear swelling was inhibited by SR140333 in wild-type and TRPV1 knockout mice. Repeated administration of mustard oil maintained 35% oedema in TRPV1 knockout animals and the lack of TRPV1 receptors did not alter the leukocyte accumulation. In contrast repeated treatment caused about 20% ear oedema in Sv129+C57BL/6 wild-type mice but the absence of NK(1) receptors significantly decreased the response. Neutrophil accumulation showed similar values in both groups. This study has revealed that mustard oil can act via both neurogenic and non-neurogenic mechanisms to mediate inflammation in the mouse ear. Importantly, the activation of the sensory nerves was still observed in TRPV1 knockout mice indicating that the neurogenic inflammatory component occurs via a TRPV1 receptor independent process.