Axonal protection in experimental autoimmune neuritis by the sodium channel blocking agent flecainide.

Inflammatory demyelinating neuropathies such as Guillain-Barre syndrome (GBS) and its animal model, experimental autoimmune neuritis (EAN), are typically acute monophasic diseases of the PNS that can leave affected individuals with permanent disability due primarily to axonal degeneration. The mechanisms underlying the degeneration are not understood, but we have previously shown in vitro and in vivo that axons can degenerate when exposed to the inflammatory mediator nitric oxide, and that axons can be protected by application of the sodium channel-blocking agent, flecainide. Here we examine whether flecainide administration can similarly reduce axonal degeneration in the periphery in animals with EAN. EAN was induced in Lewis rats (n = 116, in three independent trials), and rats received either flecainide (Flec) (30 mg/kg/day) or vehicle (Veh) from the onset of disease expression. Flecainide administration significantly reduced the mean (SD) scores for neurological deficit at both the peak of disease (Flec: 5.7 (2.7), Veh: 8.0 (3.6), P < 0.001) and at the termination of the trials 25-29 days post-inoculation (Flec: 2.2 (2.4), Veh: 4.2 (4.2), P < 0.001). Histological examination of the tibial nerve of EAN animals revealed that flecainide provided significant protection against axonal degeneration so that 80.0% of the normal number of axons survived in flecainide-treated rats compared with 62.8% in vehicle-treated rats (P < 0.01). These findings may indicate a novel avenue for axonal protection in GBS and other inflammatory demyelinating neuropathies.