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Título: | Inhibitory effect of amitriptyline on the impulse activity of cold thermoreceptor terminals of intact and tear-deficient Guinea pig corneas |
Autor: | Masuoka, Takayoshi; Gallar, Juana CSIC ORCID; Belmonte, Carlos CSIC ORCID | Fecha de publicación: | 2018 | Editor: | Mary Ann Liebert | Citación: | Journal of Ocular Pharmacology and Therapeutics 34(1-2): 195-203 (2018) | Resumen: | [Purpose]: Chronic dryness of the ocular surface evokes sensitization of corneal cold-sensitive neurons through an increase of sodium currents and a decrease of potassium currents, leading to the unpleasant dryness and pain sensations typical of dry eye disease. Here, we explored the effects of amitriptyline, a voltage-gated Na+ channel blocker used for the treatment of depression and chronic pain, on nerve terminal impulse (NTI) activity of cold-sensitive nerve terminals recorded in intact and tear-deficient guinea pig corneas. [Methods]: Main lachrymal gland was surgically removed in anesthetized guinea pigs to induce chronic tear deficiency. Four to 6 weeks afterward, animals were sacrificed and both corneas placed in a perfusion chamber superfused at 34°C. Thermal stimuli were induced by changing the solution temperature from 34°C to 20°C (cooling ramp) and from 34°C to 50°C (heating ramp). Spontaneous and stimulus-evoked NTIs of cold-sensitive nerve terminals were recorded before, during, and after perfusion with solutions containing amitriptyline at different concentrations (3–30 μM). [Results]: Perfusion with amitriptyline inhibited irreversibly and in a concentration-dependent manner the spontaneous NTI activity of cold thermoreceptors of intact corneas. This effect was less evident in tear-deficient corneas. In addition, amitriptyline (10 μM) attenuated the maximal response to cooling ramps without changing cold threshold in intact but not in tear-deficient corneas. Only cold thermoreceptors with low cooling threshold values were sensitive to amitriptyline. [Conclusion]: Amitriptyline effectively reduces the activity of cold thermoreceptors, although its efficacy is different in intact and tear-deficient corneas, which might be due to the changes induced by ocular dryness in the expression of the various voltage-gated Na+ channels responsible of the action potential generation and propagation. |
Versión del editor: | https://doi.org/10.1089/jop.2017.0066 | URI: | http://hdl.handle.net/10261/308519 | DOI: | 10.1089/jop.2017.0066 | E-ISSN: | 1557-7732 |
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