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M. C. Acosta, C. Luna, T. Donovan-Rodriguez, J. Gallar, J. Gallar, C. Belmonte; The Paradoxical Response to Heat of Corneal Cold Nerve Terminals. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2564. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To study the characteristics of the response to noxious heating (the so-called paradoxical response, PR) of cold nerve terminals (CNT) recorded from guinea-pig corneas in vitro.
Whole eyes or isolated corneas were mounted in a recording chamber and superfused with physiological saline at 32°C. A glass recording electrode (tip diameter ~50µm) filled with physiological saline was applied to the corneal epithelial surface with light suction. Thermal stimulation was performed changing the temperature of the solution from 32ºC down to 20°C or up to 52°C. Effects of capsaicin (CAP, 1µM), capsazepine (CPZ, 10-50µM), ruthenium red (RR, 10-100µM) and BCTC (10 µM) on thermosensitivity were also tested. Spontaneous and stimulus-evoked nerve impulses occurring in single corneal CNT were recorded using focal extracellular recording techniques. The characteristics of the responses to cooling and heating, and the effects of CAP were analyzed in CNT with (PR+) and without paradoxical response (PR-). TRPV1 blockers CPZ and RR were tested in CNT-PR+.
All corneal CNTs increased their basal firing frequency (7.9±0.3 imp/s, n=188) in response to cooling and decreased their discharge rate when warming the bath solution from 32ºC, 94% of them being silenced above 37ºC. Also, 36% of CNTs showed subsequent increases in impulse frequency during heating in the noxious range (above 44ºC). Mean discharge rate in response to heat was 6.2±0.5 imp/s, with a peak frequency of 17.0±1.6 imp/s at 52ºC. Response to cooling presented similar characteristics in PR+ and PR- cold nerve terminals. 95% of PR+ significantly increased their firing frequency in response to capsaicin, versus only a 13% of PR-. Capsazepine and RR blocked the response to CAP without affecting the response to heating. BCTC reduced the amplitude of the PR by 50%.
One third of corneal nerve terminals sensitive to cold also responded to heat. This PR seems to be associated with expression of TRPV1 channels, responsible for the sensitivity to the pungent agent capsaicin. However, the absence of blockade of PR by CPZ and RR suggests that heating has a complex effect on the excitability of corneal nerve terminals.
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