Sympathetic neurons modulate plasma extravasation in the rat through a non-adrenergic mechanism.

A blister model of inflammation in the rat hind footpad was used to study the possible interaction between noradrenergic sympathetic fibres and primary afferent unmyelinated fibres which contain substance P (SP), the putative mediator of neurogenic inflammation. Plasma protein extravasation (PE) was used as a measure of the response of post-capillary venules to SP perfused over the blister base. In rats treated with 6-hydroxydopamine (6-OHDA, 75 mg/kg/day for 3 days intraperitoneally) PE was reduced by 42%. However, in rats treated by local perfusion of the blister base with noradrenaline (1 mumol/L) PE was also reduced. As prostaglandins have been postulated to effect some sympathetically mediated responses, PGE1 (1 mumol/L) was perfused over the blister base and found to enhance the response to SP. The results indicate that sympathetic noradrenergic neurones may contribute to SP-induced plasma extravasation by a sensitising mechanism independent of noradrenaline.