1704 A. S. St u¨rzebecher and others J Physiol 588.10 activity (Zimmermann et al., their Fig. S6A). In our study we show that cutaneous ﬁbres of Tg-t-MrVIa mice have signiﬁcantly reduced ﬁring rates after stimulation with cold ramps (from 25◦C to 0◦C) without the concurrent application of menthol, indicating that TTX-R VGSC currents sustain the ability of neurones to ﬁre APs at very low temperatures. Thus the presence of TTX-R VGSC current is not only responsible for the detection of mechanical stimuli in the cold, but also for the detection of noxious cold per se. The apparent discrepancy between our study and that of Zimmermann and colleagues might be attributed to the differences in the protocols used to measure cold-induced responses (a cooling ramp from 30◦C to 10◦C was used by Zimmermann et al., Figure 4. Tg-t-MrVIa adult mice show reduced inﬂammatory hyperalgesia and insensitivity to cold pain A, no differences in inﬂammatory thermal hyperalgesia induced by intraplantar injection of carrageenan were observed between wild-type (Wt) and Tg-t-MrVIa mice (n = 10 mice). B, induced inﬂammation causes mechanical hyperalgesia in Wt mice (peak at 4 h) and signiﬁcantly reduced hyperalgesia in Tg-t-MrVIa (n = 10 mice). Dashed line indicates baseline pain response. C, nocifensive cold responses scored during 90 s on a 0◦C-cooled plate showed signiﬁcantly reduced responses to noxious cold in Tg-t-MrVIa mice (n = 10 mice). D, temperature pre- ference tests quantifying the time mice spent in either of two plates kept at 30◦C and 10◦C (n = 8 mice). E, histogram indicating the ﬁring frequency of cold-sensitive C-ﬁbres with a threshold >10◦C over a cooling gradient from 30 to 0◦C. The ﬁring frequency did not differ between Wt and Tg-t-MrVIa mice (ﬁbres: n = 8–12 ﬁbres per group). F, histogram indicating the ﬁring frequency of cold-sensitive C-ﬁbres with a threshold < 10◦C responding to noxious cold stimuli over a cooling gradient from 30 to 0◦C. The ﬁring frequency of cooling units with a threshold below 10◦C is signiﬁcantly reduced in Tg-t-MrVIa compared to Wt mice (ﬁbres: n = 4–8 ﬁbres per group). The lower trace corresponds to the cold ramp stimuli used in both cases. P > 0.05 two-way ANOVA in A and E; P < 0.05 two-way ANOVA in B and F; P < 0.05 t test in C. C 2010 The Authors. Journal compilation C 2010 The Physiological Society