Supplementary Figure 7: OB-1 treatment in additional pain models. | Nature Neuroscience

Supplementary Figure 7: OB-1 treatment in additional pain models.

From: Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

Supplementary Figure 7

(a) Development of tactile-evoked pain using the spared nerve injury (SNI) model. Paw withdrawal thresholds (PWTs) are displayed; note that wild type mice develop a prolonged tactile-evoked pain ipsilateral to the injury. Two-way ANOVA: SNI, ipsi vs. Sham, ipsi, P < 0.0001; numbers indicate adult mice treated (two cohorts); data are displayed as mean of individual median PWTs ± s.e.m.. (b) PWTs are displayed, showing no alleviation of tactile-evoked pain behavior after local OB-1 treatment. Mann-Whitney U-test: SNI vs. OB-1, P > 0.9999; numbers indicate adult mice treated (two cohorts); data are displayed as mean of individual median PWTs ± s.e.m.. (c) Stoml3 copy number derived from lumbar DRG L4 - L6 (two mice per preparation) determined using real-time PCR showing no up-regulation of Stoml3 mRNA after SNI. Mann-Whitney U-test: naïve, ipsi vs. SNI, ipsi, P > 0.9999; numbers indicate RNA preparations, data are displayed as mean copy number ± s.e.m.. (d-g) A single dose of NGF (1 mg/kg body weight) was injected i.p. into adult mice to induce hyperalgesia in wild type and Stoml3-/- mice. (d,e) PWT or paw withdrawal latencies (PWL) are displayed before and after NGF-induced hyperalgesia in wild type and Stoml3-/- mice showing that prominent symptoms of thermal and mechanical hyperalgesia were not different between the genotypes. (f,g) Both, PWTs and PWLs, were measured in response to OB-1 before and after systemic NGF-injection, note that OB-1 does not alleviate NGF-induced mechanical (g) or thermal (h) hyperalgesia. Two-way ANOVA: PWT WT vs. Stoml3-/- P = 0.6067 (g); PWL WT vs. Stoml3-/- (e) P = 0.1078. Mann-Whitney U-test: PWT vehicle paw naïve vs. OB-1 paw naive, P = 0.3615; PWL Vehicle paw naïve vs. OB-1 paw naïve, P = 0.699. Wilcoxon matched-pairs signed rank test: PWT syst. NGF vs. syst. NGF + OB-1 (f), P = 0.125; PWL syst. NGF vs. syst. NGF + OB-1, P = 0.1563; numbers indicate adult mice examined; data are displayed as mean of individual median PWTs (d,f) or PWLs (e,g); error bars indicate s.e.m.. *** P < 0.001 ns nonsignificant.

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