Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis

Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60–65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.