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Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2016 Sep 15; Vol. 787, pp. 2-8. Date of Electronic Publication: 2016 Jun 03. - Publication Year :
- 2016
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Abstract
- Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34°C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34°C to 15°C) activity before and in presence of lacosamide 100µM and lidocaine 100µM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0±1.1 vs. 5.2±0.7imp/s; P<0.05) and cold response (21.2±1.7 vs. 16.8±1.3imp/s; P<0.05) as well as reduced cold threshold (1.5±0.1 vs. 2.8±0.2 Δ°C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Acetamides therapeutic use
Animals
Cornea metabolism
Dry Eye Syndromes drug therapy
Dry Eye Syndromes metabolism
Female
Guinea Pigs
Lacosamide
Male
Tears metabolism
Acetamides pharmacology
Cold Temperature
Cornea innervation
Dry Eye Syndromes physiopathology
Nerve Endings drug effects
Nerve Endings physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 787
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27263827
- Full Text :
- https://doi.org/10.1016/j.ejphar.2016.05.044