Figure 7. HMWH anti-hyperalgesia is attenuated by a PI3Kγ inhibitor.
A. Male rats received oxaliplatin (2 mg/kg, i.v.) or saline (i.v.) on day 0. On day 7, a PI3Kγ inhibitor (AS605240, 1 μg/ 5 μL, i.d.) or vehicle (5 μL, i.d.) was injected. Ten minutes later, rats received an injection of HMWH (1 μg/5 μL, i.d.) or vehicle (5 μL, i.d.); mechanical nociceptive threshold was evaluated on days 0 and 7 after administration of oxaliplatin, and again 30 min after intradermal HMWH or vehicle. Oxaliplatin decreased mechanical nociceptive threshold on day 7 (F(8,40)= 61.33, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). HMWH-induced anti-hyperalgesia was attenuated in the rats treated with the PI3Kγ inhibitor (F(8,40)= 61.33, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.
B. Male rats received paclitaxel (1 mg/kg, i.p.) every other day for a total of 4 doses (days 0, 2, 4 and 6). On day 7, approximately 24 h after the last dose of paclitaxel, a PI3Kγ inhibitor (AS605240, 1 μg/ 5 μL, i.d.) or vehicle (5 μL, i.d.) was injected. Ten minutes later, rats received an injection of HMWH (1 μg/5 μL, i.d.) or vehicle (5 μL, i.d.) and mechanical nociceptive threshold was evaluated on day 0 and day 7 after the 1st dose of paclitaxel, and then again 30 min after HMWH or vehicle. The PI3Kγ inhibitor attenuates HMWH anti-hyperalgesia (F(8,40)= 79.37, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.