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. 2017 Dec 14;10(2):304–314. doi: 10.1080/19420862.2017.1409320

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© 2018 The Author(s). Published with license by Taylor & Francis Group, LLC

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 6. — Pharmacodynamic analyses of lead BBB targeting hIgG1TM-IL-1RA fusions in Seltzer PNL model of mechanical hyperalgesia. Determination of the effect of s.c. dosed lead BBB-IL-1RA fusions (BBB-IL-1RA) on PNL induced mechanical hyperalgesia via measurement of the ratio of pressure applied to ipsilateral and contralateral hind paws. Sciatic nerve ligation surgery occurred at base (day 0) and BBB-IL-1RA administered 10 or 12 day post surgery. Ipsilateral/contralateral ratio was followed for a further 4 days. (A) Measurement of the analgesic effect of BBBt0626-IL-1RA 100 mg/kg (▾), BBBt0632-IL-1RA 100 mg/kg (♦) and BBBt0726-IL-1RA 100 mg/kg (o) compared to Op + isotype control-IL-1RA 100 mg/kg (▴) and Sham + PBS 10 ml/kg (•). N = 9–10 per group. Data analyzed using 2 way ANOVA with time and treatment as dependent factors. Subsequent statistical significance obtained using Tukey's Post Hoc test. *** P<0.001 Op + Control-IL-1RA vs Op + BBBt0626-IL-1RA; + P<0.05, +++ P<0.001 Op + Control-IL-1RA vs Op + BBBt0632-IL-1RA; # P<0.05, ### P<0.001 Op + Control-IL-1RA vs Op + BBBt0726-IL-1RA. (B) Analgesic effect of 100 (o), 50 (♦) and 25 mg/kg (▾) of BBBt0626-IL-1RA dosed s.c. compared to isotype control-IL-1RA at 100 mg/kg (▴) and Sham + PBS 10 ml/kg (•). N = 7–13 per group/time point. (C) Analgesic effect of a repeat dose of 100 mg/kg of BBBt0626-IL-1RA (▾) 24 h after initial dose when compared to isotype control-IL-1RA 100 mg/kg (▴), Op + PBS 10 ml/kg (▪) and Sham + PBS 10 ml/kg (•). N = 8–10 per group. Data analyzed using 2-way ANOVA with time and treatment as dependent factors. Subsequent statistical significance obtained using Bonferroni's Post Hoc test. *** P<0.001 Op + Control-IL-1RA vs Op + BBBt0626-IL-1RA. (D) Analgesic effect of a repeat dose of 100 mg/kg of BBBt0626-IL-1RA (▾) 4 days after initial dose when compared to isotype control-IL-1RA 100 mg/kg (▴), Op + PBS 10 ml/kg (▪) 10 and Sham + PBS 10 ml/kg (•). N = 9–10 per group. Data analyzed using 2-way ANOVA with time and treatment as dependent factors. Subsequent statistical significance obtained using Bonferroni's Post Hoc test. *** P<0.001 Op + Control-IL-1RA vs Op + BBBt0626-IL-1RA.