Figure 4. HMWH anti-hyperalgesia is attenuated by a RhoA inhibitor.
A. Male rats received oxaliplatin (2 mg/kg, i.v.) or saline (i.v.) on day 0. On day 7, a ROK inhibitor (a component of RhoA signaling pathway) (Y27632, 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 7 days after administration of oxaliplatin, and then again 30 min after intradermal HMWH or vehicle. Results are presented as mechanical nociceptive threshold, in grams. Oxaliplatin decreased mechanical nociceptive threshold measured 7 days after its administration (F(8,40)= 106.85, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). Anti-hyperalgesia induced by HMWH was attenuated by the ROK inhibitor (F(8,40)= 106.85, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.
B. Paclitaxel was administered intraperitoneally (1 mg/kg, i.p.), in male rats, 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 RhoA inhibitor (Y27632, 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 evaluated on days 0 and 7 after the 1st paclitaxel injection, and then again 30 min after HMWH or vehicle. Paclitaxel decreases mechanical nociceptive threshold on day 7 after its first dose (F(8,40)= 118.45, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). Intradermal administration of RhoA the inhibitor attenuates HMWH-induced anti-hyperalgesia (F(8,40)= 118.45, ****p=0.0010; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.