Effects of Ralfinamide, a Na channel blocker, on firing properties of adult rat dorsal root ganglia nociceptive neurons

Abstract

Ralfinamaide (RM), a Na+channel blocker, suppresses cyclophosphamide and acetic acid-induced bladder hyperactivity. It is presumed that RM elicits these effects by decreasing the excitability of capsaicin sensitive (CAP-S) bladder afferent nerve. In present study, we investigated the effects of RM on Na+ currents and action potentials (AP) in rat dorsal root ganglion (DRG) neuron using whole cell patch clamp techniques. RM (25 and 50 μM) inhibited in a frequency-dependent manner TTX-resistant Na currents. Long depolarizing pulses (600 ms) elicited two types of firing patterns (phasic, 1AP and tonic, 4–10 APs) in DRG neurons. In CAP-S tonic neurons, RM (25 μM) reduced the number of APs evoked by 500 pA from 10.6 ± 1.8 to 1.1 ± 0.1. In phasic CAP-S neurons treated with substance P (SP, 0.5 μM) that increased firing from 1.0 ± 0.1 to 4.7 ± 0.3 APs. RM reduced the number of APs to 1.5 ± 0.5. RM also increased the AP threshold and decreased the overshoot of APs. These data suggest that in CAP-S phasic DRG neurons unmasking of tonic firing which can be induced by suppression of A-tyep K+ channels by exposure to SP or chronic bladder irritation can be reversed by blocking Na+ channels with RM.