Cold transduction in peripheral thermoreceptors involves a cold-and menthol-activated cation channel (Reid & Flonta, 2001), one of the TRP family (McKemy et al. 2002; Peier et al. 2002). Neurones expressing this channel depend for survival on TrkA, the nerve growth factor (NGF) receptor (Peier et al. 2002). Here we have tested whether NGF also alters the channel’s properties.

Dorsal root ganglion (DRG) neurones were cultured from adult rats (killed by CO₂ inhalation and decapitation). After 2Ð4 days, cells were loaded with the Ca²⁺-sensitive dye Calcium Green-1 AM, adapted at 32 °C and imaged during cooling ramps from 37 to 18 °C; whole-cell recordings were made using the amphotericin perforated patch configuration.

The Ca²⁺-induced fluorescence increase on cooling (ΔF) as a fraction of basal fluorescence (F₀) was larger in cold-sensitive neurones cultured with 50 ng ml^-1 NGF 7S (40 ± 16 %, mean ± S.D., n = 205) than without NGF (34 ± 16 %, n = 48; P = 0.03, Student’s unpaired t test) and the threshold temperature was also higher (31.4 ± 3.8 °C, n = 56 vs. 28.1 ± 3.4 °C, n = 48; P < 0.001). This threshold difference was accentuated by 100 mM (-)-menthol (NGF, 35.4 ± 4.0 °C, n = 26; no NGF, 29.9 ± 8.0 °C, n = 12; P = 0.008). The cold-induced depolarisation was larger in neurones cultured with NGF (30.5 ± 8.9 mV, n = 30 vs. 20.4 ± 8.3 mV, n = 16; P < 0.001) and its threshold was higher (33.6 ± 2.9 °C, n = 29 vs. 28.3 ± 3.8 °C, n = 13; P < 0.001).

In neurones cultured with NGF, cooling activated an inward current with a threshold of 31.3 ± 2.4 °C (n = 42) and an amplitude at 18 °C of 139 ± 83 pA (n = 41); without NGF, the current activated at 28.6 ± 2.9 °C (n = 13; P = 0.002) and its amplitude was halved (70 ± 50 pA, n = 13; P = 0.007). NGF did not change the proportion of cold-sensitive neurones (NGF, 67/923, 7.3% no NGF, 21/297, 7.1 %).

We conclude that NGF increases the amplitude and temperature sensitivity of the cold- and menthol-activated current in DRG neurones that already express it. As well as suggesting intracellular mechanisms that may modulate the channel, this indicates that the NGF-induced sensitisation of nociception in conditions like inflammation is likely to be accompanied by an increase in cold sensitivity.

Financial support was from the Romanian Ministry of Education (World Bank grant C-326), NATO and The Physiological Society.

All procedures accord with current local guidelines.