This study was designed to determine if the Amazonian medicinal sangre de g
rado, confers benefit by suppressing the activation of sensory afferent ner
ves. Methods: (i) vasorelaxation of rat mesenteric arteries in response to
calcitonin gene-related peptide; (ii) rat paw edema in response to protease
-activating peptide receptor 2-activating peptide; (iii) rat paw hyperalges
ia in response to low-dose protease-activating peptide receptor 2-activatin
g peptide or prostaglandin E-2; (iv) gastric hyperemia in response luminal.
capsaicin; (v) a clinical trial of a sangre de grado balm in pest control
workers. The parent botanical was fractionated for evaluation of potential
active components. In preconstricted rat mesenteric arteries, highly dilute
d sangre de grado (1:10,000) caused a shift to the right of the calcitonin
gene-related peptide dose-response curve (p<0.01). Paw edema in response to
protease-activating peptide receptor 2-activating peptide (500 <mu>g) was
reduced by as single topical administration sangre de grado balm (1% concen
tration, p<0.01) for at least 6 h. Hyperalgesia induced by either low-dose
protease-activating peptide receptor 2-activating peptide (50 <mu>g) or pro
staglandin E-2 was prevented by sangre de grado balm. A fraction possessing
analgesic and capsaicin antagonistic properties was isolated and high-perf
ormance liquid chromatography and gas chromatography mass spectrometry anal
ysis indicated that it was a proanthocyandin oligomer. In pest control work
ers, sangre de grado balm (Zangrado) was preferred over placebo, for the re
lief of itching, pain, discomfort, edema, and redness in response to wasps,
fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subject
s reported relief within minutes. We conclude that sangre de grado is a pot
ent inhibitor of sensory afferent nerve mechanisms and supports its ethnome
dical use for disorders characterized by neurogenic inflammation.