Cutaneous responses to substance P and calcitonin gene-related peptide in chronic urticaria: the effect of cetirizine and dimethindene

Background: Neuropeptides appear to participate in the pathogenesis of: chr onic urticaria. The purpose of this study was to investigate the cutaneous responses to substance P (SP) and calcitonin gene-related peptide (CGRP) in delayed pressure urticaria patients (DPUpt) and chronic idiopathic urticar ia patients (CIUpt) compared to healthy adults (HA), and also to evaluate t he effect of H-1-antagonists on these responses. Methods: Wheal (W) and flare (F) reactions to intradermally (ID) injected S P, CGRP, histamine (H), and diluent controls were evaluated in nine CIUpt, nine DPUpt, and nine HA at 3, 7, 15, 30, 60, and 120 min after injection. M aximal W and F, area under curve (AVC), and time of W and F disappearance w ere calculated at baseline and 4 h after a single dose of 20 mg cetirizine (Ce), 4mg dimethindene (Di), or placebo (P), in a double-blind, placebo-con trolled (DBPC), crossover, randomized study. Results: CIUpt exhibited enhanced and longer lasting W reactions to SP and CGRP (AUC: P<0.05) than HA; SP- and CGRP-induced F (at maximal concentratio n) were larger and longer lasting in CIUpt than in HA (P<0.003 and P=0.004, respectively). In the DPU group, SP-induced W and F responses were interme diate in magnitude compared to CIUpt and HA. In HA, SP-induced flares were significantly suppressed only by Ce (P<0.020), while both Ce and Di affecte d SP-induced W and F in the two patient groups (P<0.05). CGRP-induced flare inhibition by the two Hi-antagonists was also greater in the urticaria pat ient groups than in HA. Conclusions: CIUpt and, to a lesser extent, DPUpt showed enhanced SP- and C GRP-induced W and F reactions. CGRP elicited an immediate W and F response, followed by prolonged erythema. H-1-antagonists partially affected W and F reactions to SP and only the F response induced by CGRP; this effect was m ore pronounced in the urticaria patient groups than in HA. Overall, W and F cutaneous responses to SP were suppressed to a greater extent by Ce than D i.