Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals.
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.
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain; Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
Illés
I
Kovács
Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
Lóránt
L
Dienes
Department of Ophthalmology, Semmelweis University, Budapest, Hungary.
Kristóf
K
Perényi
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain.
Susana
S
Quirce
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain.
Carolina
C
Luna
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain.
Kamila
K
Mizerska
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain.
M Carmen
MC
Acosta
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain.
Carlos
C
Belmonte
Instituto de Neurociencias, Universidad Miguel Hernández - CSIC, San Juan de Alicante, Spain. Electronic address: juana.gallar@umh.es.
Juana
J
Gallar
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003080:Cold Temperature; D003315:Cornea / Q000294:innervation* / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D000078334:Lacosamide; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000502:physiology*; D013666:Tears / Q000378:metabolism
D000081:Acetamides; D000078334:Lacosamide
Cold thermoreceptors; Dry eye; Hyperexcitability; Lacosamide; Sodium channels