Wienholtz NKF, Christensen CE, Coskun H, et al. - Given that signaling neuropeptides including pituitary adenylate cyclase-activating polypeptide (PACAP), a regulator of vasodilation and edema, are upregulated in rosacea skin, researchers sought to assess PACAP38-induced rosacea features and examine whether a 5-HT_1B/1D receptor agonist could reduce these features. In total, 35 patients with erythematotelangiectatic rosacea received an intravenous infusion of 10 pmol/kg/min of PACAP38 followed by an intravenous infusion of 4 mg sumatriptan or placebo (saline) on two study days in a double-blind, randomized, placebo-controlled and crossover trial. According to results, PACAP38 increased the blood flow of facial skin by 90%, dilated the superficial temporal artery by 56%, and induced prolonged flushing and facial edema. A clinical experimental model of rosacea features has been established and it has been shown that sumatriptan has been able to attenuate PACAP38-induced rosacea flushing and edema. Findings support a key role of PACAP38 in the pathogenesis of rosacea flushing. Whether rosacea can be improved by PACAP38 inhibition remains uncertain.