Nociceptor activation and protein extravasation induced by inflammatory mediators in human skin

Protein extravasation (PE) is known to play an important role in inflammato ry conditions. In this study we used dermal microdialysis to apply inflamma tory mediators (histamine, bradykinin, serotonin) to human skin. Locally in duced PE was compared to pain ratings and axon reflex erythema measured sim ultaneously. Linear microdialysis capillaries (outer diameter 0.4 min, cut- off 3000 kDa) were inserted intracutaneously at a length of 1.5 cm in the v olar forearm of healthy volunteers. The capillaries were perfused with Ring er's solution at a constant flow rate of 4 mul/min. The perfusate was sampl ed at 15-min intervals and was analysed for total protein concentration. Af ter a baseline of 60 min, the perfusion was switched to inflammatory mediat ors for 30 min and then back to vehicle again. Sensations evoked by the sti mulation were assessed on a visual analogue scale and visible axon reflex e rythema was measured planimetrically. Dose-dependent increases in PE could be assessed for all inflammatory media tors tested. Bradykinin (10(7) M) induced a significant PE, whereas seroton in was effective only at a concentration of 10(3) M. While serotonin in low er concentrations induced moderate burning pain and an axon reflex flare bu t no PE, bradykinin provoked PE without pain or axon reflex flare at a conc entration of 10(7) M. Application of histamine similarly evoked PE at lower concentrations as compared to the induction of itch sensation and axon ref lex flare. It is concluded that there is no link between nociceptor activation and pro tein extravasation induced by inflammatory mediators in healthy human skin. (C) 2001 European Federation of Chapters of the International Association for the Study of Pain.