Dvorak M, Watkinson A, McGlone F, Rukwied R
Unilever Research & Development Port Sunlight, Wirral, UK.
Inflamm Res. 2003 Jun;52(6):238-45. doi: 10.1007/s00011-003-1162-z.
In the present study we examined the effects of the cannabinoid receptor agonist HU210 on histamine-evoked somatosensory and vascular responses in humans.
Two sets of experiments were performed, in which twelve (Study 1, iontophoresis) and six participants (Study 2, microdialysis) were recruited.
HU210 was administered peripherally by skin patch (50 mM) or dermal microdialysis (5 mM), whereas histamine was applied by iontophoresis (50 microAmps) or dermal microdialysis (5 microM).
Skin blood flow was monitored by laser Doppler, widespread flare reaction was evaluated planimetrically, extravasation of plasma proteins was measured in the dialysate and perceived itch was recorded using a visual analogue scale. Data were evaluated by analysis of variance.
Experimentally induced itch was significantly reduced by peripheral administration of HU210 (p < 0.05). Additionally, skin blood flow and neurogenic mediated flare responses were attenuated (p < 0.003 and p < 0.03, respectively), whereas protein extravasation due to histamine was enhanced by co-administration of HU210, as investigated by dermal microdialysis.
In humans peripheral administration of a cannabinoid receptor agonist attenuates histamine-induced itch. The observation that protein extravasation was not decreased demonstrates that the alleviation of itch is not due to an anti-histaminergic property of HU210. The reduced neurogenic flare reaction indicates an attenuated antidromic nerve fibre activation and neuropeptide release.
在本研究中，我们检测了大麻素受体激动剂HU210对人体组胺诱发的体感和血管反应的影响。
进行了两组实验，招募了12名参与者（研究1，离子导入法）和6名参与者（研究2，微透析法）。
HU210通过皮肤贴片（50 mM）或皮肤微透析（5 mM）进行外周给药，而组胺通过离子导入法（50微安）或皮肤微透析（5微摩尔）给药。
用激光多普勒监测皮肤血流，用平面测量法评估广泛的潮红反应，在透析液中测量血浆蛋白外渗，并使用视觉模拟量表记录感觉到的瘙痒。数据通过方差分析进行评估。
外周给予HU210可显著减轻实验诱导的瘙痒（p < 0.05）。此外，皮肤血流和神经源性介导的潮红反应减弱（分别为p < 0.003和p < 0.03），而通过皮肤微透析研究发现，HU210联合给药可增强组胺引起的蛋白外渗。
在人体中，外周给予大麻素受体激动剂可减轻组胺诱发的瘙痒。蛋白外渗未降低的观察结果表明，瘙痒的缓解并非由于HU210的抗组胺特性。神经源性潮红反应的减弱表明逆行性神经纤维激活和神经肽释放减弱。
