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

Figure 8.

Figure 8.

Cold sensitization by XE991 and camphor requires TRPM8. A, Averaged histogram of cold sensitization by XE991 10 μm in bins of 2 s in wild type (wt; black bars, n = 10 CMCH) and TRPM8−/− (white bars, n = 8). XE991 sensitization to cold was present in fibers from C57BL/6 (n = 8) and TRPM8+/+ (n = 2) but not in TRPM8−/− fibers. Lower trace, Time course of cold stimulus. Right, Bar chart summarizing XE991 sensitization to cold per 60 s cold stimulus in both genotypes (wt: 19.9 ± 4.5–40 ± 6.5; p = 0.02, t test; TRPM8−/−: 6.2 ± 1.1–2.7 ± 0.8). B, Correlation between activation threshold temperature of cold nociceptors (CMC) and cold sensitization by XE991 plotted as the fold increase in response magnitude (action potentials per cold stimulus of 60 s); dotted line, 0.95 confidence interval. C, Averaged histogram of cold sensitization by camphor in bins of 2 s recorded from TRPM8+/+ (black bars, n = 18 CMCH fibers) and TRPM8−/− (white bars, n = 10). The sensitization to cold of camphor was reproduced in wt but not in TRPM8-deficient fibers. Lower trace, Time course of cold stimulus. Right, Bar chart summarizing camphor sensitization to cold per 60 s cold stimulus in both genotypes (wt: 14.2 ± 4.3–37.6 ± 12.6; p = 0.08, t test; TRPM8−/−: 7.8 ± 1.6–6.1 ± 1.7. D, Correlation between activation threshold temperature of cold nociceptors and cold sensitization by camphor plotted as the fold increase in response magnitude (action potentials per cold stimulus of 60 s) for 15 CMC fibers. E, Mean firing frequency of corneal cold thermoreceptors from C57BL/6 mice in control solution (dotted line), in camphor 1 mm (black circles) and 10 mm (white circles). The figure displays the activity before (10 s) and during a dynamic cooling ramp from 34 to 20°C illustrated in the bottom trace. Inset, Mean slope (see Materials and Methods) of the change of frequency between the cooling threshold and the peak frequency versus temperature during dynamic cooling ramps (dotted line): 9.1 ± 1.7 versus camphor 1 mm (black circles) 8.8 ± 3.1 impulses/s/°C and 10 mm (white circles) 0.5 ± 0.3 impulses/s/°C; n = 7; paired t test: p = 0.003). Errors bars represent the SEM. F, Mean activity, shown as impulses per second at 34°C, is increased by the application of camphor 1 mm for 3.4 min, while the maximum response during a dynamic cooling ramp is attenuated or blocked after application of camphor 1 or 10 mm, respectively. Ongoing activity: 3.7 ± 1.2 impulses/s (control) vs 7.5 ± 1.9 impulses/s at 1 mm (n = 7) and 3.4 ± 1.2 impulses/s at 10 mm (n = 10); paired t test, p = 0.003 and p = 0.5, respectively; peak frequency: 56.9 ± 6.7 impulses/s (control) versus 38.0 ± 5.6 impulses/s at 1 mm and 8 ± 4.4 impulses/s at 10 mm; n = 7; paired t test, p = 0.01 and p = 0.004, respectively. Errors bars represent the SEM.