Voltage-gated sodium channel Nav1.6 is required for excitability, but is not sufficient for cold sensitivity, of silent cold-sensing neurons. [A(i)] Histogram of cross-sectional areas of all cold-sensing neurons imaged in homozygous Nav1.8-Cre tdTomato mice with oxaliplatin. [A(ii)] Cumulative probability plot of cell areas in oxaliplatin-treated heterozygous and homozygous Nav1.8-Cre mice, compared by Kolmogorov-Smirnov test. [A(iii)] Bar plot showing the proportion of silent cold-sensing neurons expressing tdTomato in heterozygous and homozygous Nav1.8-Cre mice, compared using a χ2 test. n = 66 cells from three heterozygous (two males and one female) and n = 42 cells from three homozygous (one male and two females) Nav1.8-Cre mice. (B) Cumulative probability plot of cell areas in oxaliplatin-treated wild-type and Nav1.7 KO mice, compared by Kolmogorov-Smirnov test. n = 51 cells from five wild-type (one male and four females) and n = 18 cells from two Nav1.7 knockout mice (two females). (C) Heat maps (i) and quantification (ii) showing the effect of intraplantar injection of different sodium channel blockers on the number of basal and silent cold-sensing neurons in mice pretreated with oxaliplatin. [C(iii)] Line plot showing the effect of blockers on median peak response, compared using Kruskall-Wallis test followed by Dunn’s multiple comparisons test. n = 35 cells from three mice for saline (one male and two females), n = 58 cells from four mice for TTX (three males and one female), n = 36 cells from two mice for 4,9-anhydrous-TTX (two females). [D(i)] Heat map showing the effect of sodium channel activation by intraplantar veratridine injection on the activity of cold-sensing neurons. [D(ii)] Box plot showing the size of cold-sensing cells is unaffected by veratridine, compared by Mann-Whitney test. [D(iii)] Bar plot showing veratridine reduces the number of cold-sensing neurons from 39 to 31. [D(iv)] Line plot showing veratridine reduces the response magnitude of cold-sensing cells, compared by Wilcoxon matched-pairs signed rank test. n = 53 cells from three mice (three males).