Effects of mast cell degranulation on blood-nerve barrier permeability and nerve conduction in vivo.

Changes in blood-nerve barrier (BNB) integrity and nerve conduction were assessed in rat tibial nerves in which mast cell degranulation was induced by intraneural injection of Compound 48/80 (C48/80). BNB permeability changes were quantitated by the endoneurial accumulation of Evan's blue-labelled albumin (EBA). Over 24 h following intraneural injections, nerves receiving saline showed a 6-fold increase in endoneurial extravasated EBA compared to non-injected nerves. Injection of 250 ng C48/80 produced a similar level of EBA accumulation as saline injections. Increasing the C48/80 dose to 1 microgram produced twice the EBA accumulation as control saline injections and a 12-fold increase over non-injected nerves. Tibial nerves injected with these C48/80 doses showed completely normal nerve conduction. In contrast, increasing the dose to 5 micrograms C48/80 induced, again, increased EBA accumulation over lower doses, but also significant axonal degeneration indicated by profound decreases in compound muscle action potential amplitudes measured with nerve stimulation distal to the injection site. Co-injection of Leupeptin and neutralizing anti-TNF-alpha antibodies with C48/80 failed to mitigate conduction abnormalities suggesting a direct toxic effect of C48/80 on nerve fibres. Time-kinetic studies showed rapid restoration of BNB integrity 24-48 h after injections in all nerves, but at these timepoints C48/80 injected nerves still showed significantly increased BNB permeability compared to nerves injected with saline. Neural mast cell stimulation in the absence of a primed immune response can produce profound temporary changes in blood-nerve barrier permeability and endoneurial fluid composition without affecting nerve conduction.