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. 2023 Oct 3;147(3):1025–1042. doi: 10.1093/brain/awad339

Figure 7.

Figure 7

TLR4 and RAGE antisense reverses oxaliplatin CIPN in female rats. Female rats received oxaliplatin [2 mg/kg, intravenously (i.v.)] on Day 0, and 4 days later, they were treated with intrathecal antisense-oligodeoxynucleotides (AS-ODN) or mismatch (MM)/sense (SE)-ODN (both 120 μg in 20 μl/day) against (A) TLR4 or (B) RAGE mRNA, once a day for 4 days consecutively, and then three more doses, one every other day, for a total of seven doses, over 10 days. The mechanical nociceptive threshold was evaluated from Days 0 to 28. Oxaliplatin-induced hyperalgesia was markedly reversed in the (A) TLR4 and (B) RAGE AS-ODN-treated groups of female rats, and this reversal was undiminished over the 28-day testing period. Statistical analyses for A: two-way repeated-measures ANOVA, Time × TLR4 AS-ODN interaction, F(5,50) = 64.68, P < 0.0001; TLR4 AS-ODN treatment, F(1,10) = 95.41, P < 0.0001; Bonferroni's multiple post hoc comparisons test, ****P < 0.0001 (MM-ODN versus AS-ODN); and B: two-way repeated-measures ANOVA, Time × RAGE AS-ODN interaction, F(5,50) = 77.11, P < 0.0001; RAGE AS-ODN treatment, F(1,10) = 368.2, P < 0.0001; Bonferroni's multiple post hoc comparisons test, ****P < 0.0001 (SE-ODN versus AS-ODN). n = 6 paws for each group. All data are mean ± SEM. CIPN = chemotherapy-induced peripheral neuropathy.