Electrical stimulation of the sensory saphenous nerve leads to neurogenic
edema formation in the innervated area of the paw of the anesthetized rat. Evidence suggests that the
edema formation is the result of increased microvascular permeability mediated via neurokinin NK1 receptors and increased blood flow mediated via
calcitonin gene related peptide CGRP1 receptors. Results indicate that selective receptor antagonists will only inhibit the response mediated by the specific receptor they antagonise. In the case of
neurogenic inflammation, where it is common for more than one biologically active
neuropeptide to be released concomitantly, it may be more sensible to develop agents that inhibit
neuropeptide release. The effects of some agents suggested to affect neurogenic responses are presented. The anti-inflammatory
steroid dexamethasone (1 mg/kg subcutaneously, -4 h) significantly (p < 0.01) inhibited
edema formation, but the mechanism of action is likely to be related to the general anti-
edema effect of
dexamethasone. In contrast the anti-
asthma agent
nedocromil sodium (up to 10 mg/kg intravenously, -15 min) and the
histamine H3 agonist (R)-alpha-methyl
histamine (1-10 mg/kg intravenously, -5 min) both failed to inhibit saphenous nerve induced
edema formation, despite positive results in other sensory nerve systems. The results are discussed in the context of evidence obtained using other agents in skin.