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M. Carmen Acosta, Illes Kovacs, Susana Quirce, Carolina Luna, Kamila Mizerska, Carlos Belmonte, Juana Gallar; Lacosamide Diminishes Dryness-induced Hyperexcitability of Corneal Cold Sensitive Nerve Terminals. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1798.
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Enhanced spontaneous and stimulus-evoked activity of corneal cold receptors has been observed in the experimental model of dry eye produced by lacrimal gland removal. Lacosamide is an anti-epileptic drug also used for the treatment of painful diabetic neuropathy, which blocks voltage-gated sodium channels. We explored here the effect of acute application of lacosamide on the electrical activity of corneal cold nerve terminals of lacrimo-deficient guinea pigs.
Four weeks after unilateral surgical removal of the main lacrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34 ºC for extracellular recording of cold-sensitive nerve terminal activity (NTI). The characteristics of the spontaneous activity and stimulus-evoked responses (cooling ramps from 34º to 20 ºC) NTI before and in presence of lacosamide and lidocaine (both at 100µM) were compared.
Cold nerve terminals (n=19) from dry eye corneas showed a significantly augmented spontaneous and cold-evoked NTI firing and a reduced threshold to cooling ramps in comparison with those of control animals (n=18). Lidocaine and lacosamide decreased spontaneous activity significantly (by -5.02±1.46 imp/s, p<0.001 and by -4.29±0.90 imp/s; p<0.01, respectively). Temperature decrease required to evoke the cooling response that was 1.71±0.15 ºC before drug application was augmented by lidocaine (2.91±0.34 ºC; p=0.005) but not by lacosamide (1.66±0.21 ºC; p>0.05). Also, application of lidocaine and lacosamide resulted in a significantly lower peak frequency value in response to cooling (4.71±3.32 imp/s and 14.01±2 imp/s respectively) compared to values before drug application (21.24±1.5 imp/s; p<0.001).
Lacosamide decreased significantly both the enhanced spontaneous activity and the response to cooling of corneal cold receptors, although its effects were weaker than those of lidocaine. Lacosamide may be used to reduce the hyperexcitability of corneal cold receptors caused by long term ocular dryness possibly through a direct action on voltage-gated sodium channels.
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