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Analgesic ineffectiveness of lacosamide after spinal nerve ligation and its sodium channel activity in injured neurons
Author(s) -
Hagenacker T.,
Schäfer N.,
Büsselberg D.,
Schäfers M.
Publication year - 2013
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2012.00260.x
Subject(s) - lacosamide , sodium channel , analgesic , pharmacology , neuropathic pain , sodium channel blocker , anesthesia , medicine , chemistry , sodium , epilepsy , organic chemistry , psychiatry
Background Lacosamide is a novel anti‐epileptic drug that enhances the slow‐ and not fast‐inactivating state of voltage‐gated sodium channels. Lacosamide has demonstrated analgesic efficacy in several animal studies but preclinical studies on neuropathic pain models are rare, and recent clinical trials showed no superior analgesic effects. Methods Here, we examine whether an acute or chronic administration of lacosamide (3–60 mg/kg, i.p.) attenuates pain behaviour induced by spinal nerve ligation ( SNL ). To validate the inhibitory efficacy of lacosamide on voltage‐gated sodium channels, sodium currents in naïve and SNL ‐injured dorsal root ganglion ( DRG ) neurons were recorded using whole‐cell patch clamping. Results Lacosamide only marginally attenuated thermal hyperalgesia, but not tactile allodynia when applied once 7 or 14 days after SNL and showed no analgesic effect when applied daily for 19 days. In naïve neurons, 100 μmol/ L lacosamide inhibited sodium channel currents by 58% and enhanced the slow inactivation (87% for lacosamide vs. 47% for control). In contrast, lacosamide inhibited sodium currents in injured DRG neurons by only 15%, while the effects on slow inactivation were diminished. Isolated currents from the Na V 1 .8 channel subtype were only marginally changed by lacosamide. Conclusion The reduced effectiveness of lacosamide on voltage‐gated sodium channel currents in injured DRG neurons may contribute to the reduced analgesic effect observed for the SNL model.