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  • Title: The effects of class Ic antiarrhythmics on tetrodotoxin-resistant Na+ currents in rat sensory neurons.
    Author: Osawa Y, Oda A, Iida H, Tanahashi S, Dohi S.
    Journal: Anesth Analg; 2004 Aug; 99(2):464-71, table of contents. PubMed ID: 15271726.
    Abstract:
    IV or oral administration of antiarrhythmics has been reported to be effective for relieving neuropathic pain. Recent reports have indicated that tetrodotoxin-resistant (TTX-R) Na(+) channels play important roles in the nerve conduction of nociceptive sensation. In the present study, we investigated the effects of flecainide, pilsicainide (class Ic antiarrhythmics), and lidocaine (a class Ib drug) on TTX-R Na(+) currents in rat dorsal root ganglion neurons using the whole-cell patch-clamp method. Flecainide, pilsicainide, and lidocaine reversibly blocked the peak amplitude of TTX-R Na(+) currents in a concentration-dependent manner with half-maximum inhibitory concentration values of 8.5 +/- 6.6 microM (n = 7), 78 +/- 6.9 microM (n = 7), and 73 +/- 6.8 microM (n = 7), respectively. Each drug shifted the inactivation curve for the TTX-R Na(+) currents in the hyperpolarizing direction and caused a use-dependent block. We also studied an interaction between these antiarrhythmics on TTX-R Na(+) channels. Additional application of flecainide or pilsicainide to lidocaine resulted in an additive increase of tonic and use-dependent block. These results suggest that the inhibition of TTX-R Na(+) currents of dorsal root ganglion neurons by such antiarrhythmics is attributable, at least partly, to their antinociceptive effects.
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