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

Abstract

 

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 B1 and B2 receptors in healthy and UV-B irradiated skin in human volunteers. The B1 receptor agonist des-Arg¹⁰-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.