A. Male rats received oxaliplatin (2 mg/kg, i.v.) or saline (i.v.) on day 0. Four days later, they were treated with an ODN antisense or mismatch for CD44 mRNA (120 μg/ 20 μL, i.t.), daily for 3 days. On day 7, approximately 24 h after the last intrathecal administration of ODN, HMWH was injected (1 μg/ 5 μL, i.d.). Mechanical nociceptive threshold was evaluated on day 0, and on day 4 and 7 after administration of oxaliplatin, and then 30 min after HMWH. Results are presented as mechanical nociceptive threshold in grams. Oxaliplatin decreased mechanical nociceptive threshold (i.e., produced hyperalgesia), measured 4 days after intravenous injection (F(7,35)= 97.99, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test), in both CD44 antisense- and mismatch-treated groups. HMWH attenuates the hyperalgesia induced by oxaliplatin (F(7,35)= 97.99, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test) only in the CD44 mismatch-treated group. 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). Four days after the 1st paclitaxel injection, rats were treated with an oligodeoxynucleotide (ODN) antisense or mismatch (120 μg/ 20 μL, i.t.) for CD44 mRNA, daily for 3 consecutive days. On day 7, approximately 24 h after the last dose of ODN, and the last intraperitoneal injection of paclitaxel, HMWH was injected (1 μg/ 5 μL, i.d.). Mechanical nociceptive threshold was evaluated on day 0, and 4 and 7 days after oxaliplatin, and then 30 min after HMWH. Paclitaxel decreased mechanical nociceptive threshold (i.e., produced hyperalgesia), measured 4 days (F(7,35)= 52.53, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test) after its first dose, in both CD44 antisense- and mismatch-treated groups. HMWH attenuates the hyperalgesia induced by paclitaxel in the CD44 mismatch-treated group (F(7,35)= 52.53, *p=0.0107; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.