Pharmacology of the Neurogenic Oedema Response to Electrical Stimulation of the Saphenous Nerve in the Rat

The pharmacology of the early and delayed phases of the neurogenic oedema responses to electrical stimulation of the saphenous nerve was studied in anesthetized rats using a quantitative Evans blue dye leakage technique. The immediate response to 5 min nerve stimulation was not reduced by aprotinin or mepyramine in combination with methysergide. However the response measured 10 min later and also that to 15 min nerve stimulation were reduced by these agents indicating that kinins and mast cell amines might be released after some delay, but they did not contribute significantly to the early phase of the response. Results with indomethacin indicated that prostaglandins were not involved in the later phase of the response. Bacitracin which has been reported to potentiate the sialogogic effect of substance P, the most likely candidate for primary mediator of neurogenic oedema, was without effect on the early phase of the response. Morphine, which has been suggested to inhibit stimulus-evoked substance P release from primary afferent terminals, reduced the early phase of the neurogenic oedema response but it also reduced blood pressure. Both effects were abolished by naloxone and thus it is likely that the reduction in the neurogenic oedema response was due to the depressor action of morphine. In confirmation of previous findings, capsaicin pretreatment of both adult rats and rats as neonates resulted in marked reduction of the neurogenic oedema response without effect on the vascular permeability response to substance P.