Fig. 2 | Nature Communications

Fig. 2

From: Maladaptive activation of Nav1.9 channels by nitric oxide causes triptan-induced medication overuse headache

Fig. 2

Deletion of Nav1.9 prevents NO-induced generalized allodynia in MOH mice. a Infusion of sumatriptan (0.6 mg/kg/day), but not saline solution (0.9%), decreases withdrawal thresholds to tactile stimuli applied to the hind paws of WT mice. Hind paw withdrawal threshold was tested using von Frey filaments (inset). **p < 0.01, ***p < 0.001 compared to saline with Mann–Whitney non-parametric test. Top inset: schematic of mouse treatment over time. b Changes in mechanical withdrawal thresholds of the hind paws induced by injection of SNP (0.03 mg/kg) in WT mice pre-treated (red symbols) or not (open circles) with sumatriptan. Data illustrated depict SNP responses 21 days after minipump implantation. **p < 0.01, ***p < 0.001 compared to WT saline, SNP with Mann–Whitney non-parametric test. c Hind paw withdrawal responses of sumatriptan-treated Nav1.9−/− mice compared with sumatriptan-treated WT littermates. *p < 0.05, **p < 0.01, ***p < 0.001 compared to WT with Mann–Whitney non-parametric test. d Comparison of SNP-induced changes in hind paw withdrawal thresholds in sumatriptan-treated WT mice (red symbols), saline-treated Nav1.9−/− mice (open squares) and sumatriptan-treated Nav1.9−/− mice (blue squares). All tests were made at day 21. **p < 0.01, ***p < 0.001 compared to WT sumatriptan with two-way ANOVA followed by Student–Newman–Keuls test. e Normalized periorbital withdrawal threshold plotted as a function of time after SNP injection in saline-treated WT mice (open bars), sumatriptan-treated WT mice (red bars) and sumatriptan-treated Nav1.9−/− mice (blue bars). Data illustrated depict SNP responses 21 days after pump implantation. *p < 0.05, ***p < 0.001; two-way ANOVA followed by Student–Newman–Keuls test

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