Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin.
OBJECTIVE
In the present study we examined the effects of the cannabinoid receptor agonist HU210 on histamine-evoked somatosensory and vascular responses in humans.


METHODS
Two sets of experiments were performed, in which twelve (Study 1, iontophoresis) and six participants (Study 2, microdialysis) were recruited.


METHODS
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dvorak
M
M
Unilever Research & Development Port Sunlight, Wirral, UK.
Watkinson
A
A
McGlone
F
F
Rukwied
R
R
D000287:Administration, Topical; D000328:Adult; D001369:Axons / Q000473:pathology; D063386:Cannabinoid Receptor Agonists; D002199:Capillary Permeability / Q000187:drug effects; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000633:toxicity*; D006633:Histamine Antagonists; D006801:Humans; D007478:Iontophoresis; D008297:Male; D017551:Microdialysis; D011506:Proteins / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced / Q000188:drug therapy; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D006633:Histamine Antagonists; D011506:Proteins; D000431:Ethanol; D013759:Dronabinol; D006632:Histamine; C062018:HU 211