Neuropeptide- and capsaicin-induced histamine release in skin monitored with the microdialysis technique

Mast cells are thought to be involved in neurogenic inflammation in skin, and numerous neuropeptides are known to degranulate mast cells. We monitored histamine release in skin in situ with the microdialysis method after skin challenge with neuropeptide injections (10 microM substance P, vasoactive intestinal peptide and calcitonin gene-related peptide), capsaicin injection (30 microM) and 0.1% capsaicin cream with a moist compress. Fractions were collected for 15 min each at 3.0 microliter/min. One hour after insertion of the probe, the baseline histamine level was 4.5 +/- 4.5 nM (mean +/- SD, n = 20). Substance P (250 pmol) induced histamine release peak (66.1 +/- 52.5 nM, n = 8) in the 0-15 or 15-30 min fraction. Thereafter, the histamine concentration declined steadily and rapidly and no second rise was observed. A single substance P injection was sufficient to induce major histamine release in three out of four experiments; and the release kinetics of the second injection (1 h later) mimicked that of the first injection. Vasoactive intestinal peptide (100 and 250 pmol) induced a rapid release of histamine in 4 subjects comparable to substance P, whereas calcitonin gene-related peptide (250 pmol) did not release detectable amounts of histamine in 2 subjects tested. Capsaicin induced a low and rather non-significant release of histamine in 4 out of 5 patients who received capsaicin injection and in 2 out of 5 who were treated with capsaicin cream. The present study shows that neuropeptides substance P and vasoactive intestinal peptide, but not calcitonin gene-related peptide, can induce activation of mast cells and release of histamine into the extracellular space. The low release of histamine by capsaicin suggests low levels of neuropeptides or infrequent morphological contacts between mast cells and sensory nerves in normal human skin. The microdialysis method can be used for studying skin inflammatory reactions involving mast cells.