Fig. 2.

ICOS agonist antibody (ICOSaa) promotes the resolution of mechanical hypersensitivity in paclitaxel-induced peripheral neuropathic pain. A The cohorts of mice were subjected to intraperitoneal injection of 4 mg/kg paclitaxel every other day for a cumulative dosage of 16 mg/kg according to the schema shown followed by intrathecal injection of ICOSaa or vehicle for four consecutive days. Arrows represent days of von Frey testing. Paclitaxel group represented in yellow and Ptx + ICOSaa represented in blue. B Female mice reversed mechanical allodynia after intrathecal administration of ICOSaa (two-way ANOVA, F = 4.951, p-value < 0.0001, post hoc Sidak’s, Ptx + ICOSaa vs. Ptx, p-value = 0.0318 at day 8, Ptx + ICOSaa vs. Ptx, p-value = 0.0323 at day 15, Ptx + ICOSaa vs. Ptx, p-value = 0.0001 at day 28, Ptx + ICOSaa vs. Ptx, p-value = 0.0067 at day 32, Ptx + ICOSaa vs. Ptx, p-value = 0.0.0261 at day 36), N = 8/group C Effect size was determined by calculating the cumulative difference between the value for each time point and the baseline value. The effect size difference was significant in the female cohort of mice (effect size, unpaired t test, t = 4.963, p-value = 0.0002, df = 14). D Male mice showed a trend in resolution of mechanical hypersensitivity measured with von Frey filaments after administration of ICOSaa but it was not significant (two-way ANOVA, F = 2.020, p-value = 0.0544), N = 6/group. E We did not observe any statistically significant differences between the groups in male (Effect size, unpaired t test, t = 1.533, p-value = 0.1564, df = 10). F Paw withdrawal thresholds were determined with von Frey filaments after ICOSaa treatment alone and was not significant compared to baseline measures in female mice (one-way ANOVA, F = 2.049, p-value = 0.1529), N = 8. G Motor function was assessed using the rotarod after administration of ICOSaa and compared to baseline in female mice (one-way ANOVA, F = 1.28, p-value = 0.3075), N = 8. *p < 0.05, **p < 0.01, ***p < 0.001