All nerve terminals exhibiting a repetitive background activity immediately after application of the pipette also responded readily to a cooling ramp with a robust increase in firing frequency. We classified these nerve terminals as high-background activity, low-threshold (HB-LT) cold thermoreceptor terminals; they represented 72% of the total population of cold-sensitive nerve endings found in the cornea. Mechanical pressure evoked a few NTIs in six HB-LT terminals where it was tested (
Fig. 4).
Table 2 summarizes the firing characteristics of the HB-LT cold thermoreceptor terminals. Their background activity at 34°C was usually composed of regularly appearing individual or paired NTIs, firing at a mean frequency ranging between 1.3 and 19.3 imp·s
−1 (mean 6.6 ± 1.0 imp·s
−1,
n = 26). During the initial portion of the cooling ramp, firing pattern often changed from regular beating to bursting and, after reaching a peak frequency value of 57.8 ± 3.9 imp·s
−1 at 26 ± 0.7°C, NTIs usually silenced at around 23°C, well before reaching the lowest temperature point (14–15°C). During the 30-second heating period back to the control temperature, a transient NTI discharge (mean number 102.1 ± 40 NTIs), appearing at a mean temperature of 27.5 ± 0.5°C and lasting on the average 7.5 ± 1.8 seconds, was observed in 14 out of 26 HB-LT terminals (
Fig. 4), followed again by a silence until a temperature of 31.4 ± 0.3°C was attained, at which point the NTI activity gradually recovered to the frequency that it had prior to the cooling ramp. The application of 20 μM menthol increased significantly ongoing activity of HB-LT terminals (
Table 2). Also, perfusion with 340 mOsm·kg
−1 hyperosmolal solution increased the ongoing firing frequency (from 8.0 ± 1.5 to 10.3 ± 1.6 imp·s
−1,
P < 0.05). Sixty-seven percent of the HB-LT terminals responded to a heating ramp with a transient NTI discharge (“paradoxical response”) starting at 41.9 ± 2°C (mean number of NTIs, 355.5 ± 111.4; mean duration of the firing period, 9.4 ± 2.1 seconds). Four HB-LT terminals with a paradoxical response were tested with 1 μM capsaicin; in all of them, capsaicin increased the mean firing rate at 34°C (Δ = 13.0 ± 3.5 imp·s
−1,
n = 4) and reduced the cooling threshold to temperature values 3°C to 4°C lower than the pretreatment value. Intriguingly, in two out of four terminals tested, the TRPA1 agonist AITC prolonged the duration of NTI firing during the cooling ramp to a temperature below 20°C (19.9°C and 14.4°C in the two responsive terminals).