5-Hydroxytryptamine bradykinin and histamine as mediators of inflammatory hyperesthesia

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Abstract
Changes in threshold to pressure and volume were measured in rat paws injected with 5-HT, bradykinin, or histamine separately and in combination to find out if one or more of these agents mediate hyperesthesia of experimentally inflamed rat paws, and also to assess the role of the mechanical factors imposed by the attendant edema. Subcutaneous perfusates obtained at the time of maximal hyperesthesia from yeast-inflamed paws were bioassayed for 5-HT, bradykinin, and histamine content. Intensity of hyperesthesia correlated well with dose of 5-HT or bradykinin, but not with the degree of accompanying edema. Hyperesthesia induced by 10 µg 5-HT was potentiated in paws injected simultaneously with 10 µg bradykinin. However, a 30- to 45-min delay in appearance of maximal hyperesthesia induced by 5-HT and bradykinin injected alone or in combination suggested an indirect rather than a direct effect. Perfusates from yeast-inflamed paws contained no 5-HT or histamine and only infrequently a bradykinin-like substance. We concluded that the hyperesthesia of experimentally inflamed rat paws was not mediated by a direct action on subcutaneous nerve endings of 5-HT, bradykinin, or histamine separately or in combination, and that its intensity was not indicated by the degree of attendant edema.