Genotyping and phenotyping of substance P (SP) deficient (Tac1−/−
) and CGRP receptor deficient (RAMP1−/−
) mice. PCR products of tail DNA from wildtype (WT) and Tac1−/− mice yielded 190 and 170-bp PCR fragments, respectively (A). The knockout mutant PCR fragment was shorter due to the targeted deletion. WT and mutant RAMP1−/− alleles yielded 108 and 240-bp PCR fragments, respectively. Western blot assay was used to demonstrate that RAMP1 protein expression in the hindpaw skin was abolished due to disruption in the genomic structure of the RAMP1 allele (C) Electrically evoked extravasation responses were quantified by measuring Evans blue dye content in the hindpaw skin after 5 minutes of sciatic stimulation at C-fiber intensity (D). Tac1−/− mice extravasation responses were reduced 60% vs WT mice, but no decrease in extravasation was observed in the RAMP1−/− mice (n = 6 per cohort). These results indicate that neuronal SP release can induce microvascular protein extravasation into the cutaneous interstitial space, but neuronal CGRP release is an ineffective mediator of cutaneous extravasation. **P <0.01 vs WT, #P < 0.05 vs Tac1−/−.