Ion channel blockers for the treatment of neuropathic pain.

Neuropathic pain, a severe chronic pain condition characterized by a complex pathophysiology, is a largely unmet medical need. Ion channels, which underlie cell excitability, are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain. This review highlights the biological evidence supporting the involvement of voltage-, proton- and ligand-gated ion channels in the neuropathic pain setting.

Ralfinamide administered orally before hindpaw neurectomy or postoperatively provided long-lasting suppression of spontaneous neuropathic pain-related behavior in the rat.

Ralfinamide is analgesic when applied as a single dose in rodent models of stimulus-evoked chronic pain. However, it is unknown whether its chronic application after nerve injury can suppress spontaneous chronic pain, the main symptom driving patients to seek treatment. In this study ralfinamide was administered to rats at doses producing plasma levels similar to those causing analgesia in pain patients.

Functional expression of type 1 rat GABA transporter in microinjected Xenopus laevis oocytes.

In this chapter we describe technical aspects and experimental potential of the two electrodes voltage clamp (TEVC) electrophysiological approach applied to the Xenopus oocyte-expression system. This technique is addressed to the study of a particular class of expressed proteins, those responsible to drive ion fluxes through the plasma membrane. In fact the voltage-clamp technique provides the most direct and sensitive measurement of the functional properties of ion channels and electrogenic transporters, allowing specific ion currents to be recorded under well-defined voltage conditions and temporal control.

The anti-nociceptive agent ralfinamide inhibits tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ currents in dorsal root ganglion neurons.

Tetrodotoxin-resistant and tetrodotoxin-sensitive Na+ channels contribute to the abnormal spontaneous firing in dorsal root ganglion neurons associated with neuropathic pain. Effects of the anti-nociceptive agent ralfinamide on tetrodotoxin-resistant and tetrodotoxin-sensitive currents in rat dorsal root ganglion neurons were therefore investigated by patch clamp experiments. Ralfinamide inhibition was voltage-dependent showing highest potency towards inactivated channels.

The therapeutic potential of Na+ and Ca2+ channel blockers in pain management.

Chronic pain affects a large percentage of the population, representing a socio-economic burden. Current treatments are characterised by suboptimal efficacy and/or side effects that limit their use. Among several approaches to treating chronic pain, voltage-sensitive Ca(2+) and Na(+) channels are promising targets.