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. 2013 Oct 16;33(42):16627–16641. doi: 10.1523/JNEUROSCI.1473-13.2013

Figure 1.

Figure 1.

Camphor boosts cold transduction in a subpopulation of nociceptors. A, Original recording from a cold nociceptor showing instantaneous discharge rates in response to camphor application and cooling from 30°C to 10°C. Camphor 2 mm superfused 5 min after a control cold stimulus sensitizes a menthol- and capsaicin-sensitive fiber to cooling. Interstimulus interval and drug wash-in was 5 min. Lower trace, Time course of cold stimulus and temperature thresholds of activation. Note the shift in activation threshold induced by camphor. Inset, Average spike shape. Calibration: 0.5 ms, 200 μV. B, Four-way distribution describing the percentage of mechanosensitive C-fibers of each subclass sensitized to cold by camphor (CM, temperature-insensitive nociceptor, n = 12/26; CMC, cold nociceptor, n = 6/10); CMCH, multimodal nociceptor, n = 1/9; CMH, polymodal nociceptor, n = 1/21); all, n = 20/66). C–E, Quantification of the sensitization of camphor to cold: increase in response magnitude counted as action potentials (APs) per 60 s of cold stimulus (white bars: wild type, 7.6 ± 4.5–41.8 ± 11.6, p < 0.004; striped bars: TRPV1−/−, 5.9 ± 3.1–48.3 ± 13.2; p < 0.008, Wilcoxon test; no difference between genotypes, U test; C) and peak firing frequency (open circles: wild type, 1.1 ± 0.7–4.9 ± 1.4 spikes/s; crossed circles: TRPV1−/−, 0.5 ± 0.3–7.2 ± 2.8 spikes/s; p < 0.008, Wilcoxon test; no difference between genotypes, U test; D], and rise in threshold temperature in sensitized cold-sensitive units [open rectangles: wild type, 17.7 ± 1.5°C–22.1 ± 1.8°C (only CMCH, n = 4); crossed rectangles: TRPV1−/−, 15.5 ± 0.9°C–24.3 ± 1.8°C (only CMC, n = 3), significant for pooled population, p < 0.03, Wilcoxon test; no difference between genotypes, U test; E]. F, Averaged histogram summarizing the cold responses of all sensitized nociceptors in bins of 4 s (n = 20) for TRPV1−/− (striped white and black bars) and TRPV1+/+ (blank white and black bars), camphor 2 mm induced sensitization to cold in one-third of the treated fibers (TRPV1+/+, n = 11/38; and TRPV1−/−, n = 9/28). TRPV1+/+ were congenic to C57BL/6. Lower trace, Temperature time course.