Sensitization to bradykinin B1 and B2 receptor activation in UV-B irradiated human skin

Bradykinin B1 and B2 receptors contribute to nociceptor sensitization under inflammatory conditions. Here, we examined the vascular inflammatory responses and nociceptive effects resulting from activation of B I and B2 receptors in healthy and UV-B irradiated skin in human volunteers. The B1 receptor agonist des-Arg(10)-Kallidin (10(-6) - 10(-3) M) and the B2 receptor agonist bradykinin (10(-9) - 10(-4) M) were administered by dermal microdialysis to the ventral thigh. UV-B irradiation was performed 24 h prior to the experiment with the threefold minimum erythemal dose. Pain sensation perceived during the stimulation with the bradykinin receptor agonists was estimated on a numeric scale. Local and axon reflex-induced vasodilatations were recorded by laser Doppler imaging. For protein extravasation, total protein content in the dialysate was assessed as a measure of increased endothelial permeability. In normal skin. both B1 and B2 receptor activation dose-dependently evoked pain, vasodilatation and protein extravasation. In UV-B irradiated skin, pain sensation and axon reflex vasodilatation were enhanced by both B1 and B2 agonists, whereas local vasodilatation was increased only following B1 receptor activation. The UV-B irradiation did not enhance B1 and B2 receptor-induced protein extravasation indicating a differential sensitization of the neuronal, but not the vascular response. (C) 2004 Published by Elsevier B.V. on behalf of International Association for the Study of Pain.