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. Author manuscript; available in PMC: 2023 Sep 1.
Published in final edited form as: Pain. 2021 Dec 6;163(9):1728–1739. doi: 10.1097/j.pain.0000000000002558

Figure 6. HMWH anti-hyperalgesia is attenuated by ODN antisense to PI3Kγ mRNA.

Figure 6.

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 oligodeoxynucleotide (ODN) antisense or mismatch (120 μg/ 20 μL, i.t.) for PI3Kγ mRNA, daily for 3 consecutive days. On day 7, approximately 24 h after the last dose of ODN, HMWH (1 μg/ 5 μL, i.d.) was injected. Mechanical nociceptive threshold was evaluated on days 0, 4 and 7 after administration of oxaliplatin and 30 min after HMWH. Oxaliplatin decreased mechanical nociceptive threshold (i.e., produced hyperalgesia), observed 4 days after intravenous injection in both PI3Kγ antisense- and mismatch-treated groups (F(7,35)= 103.47, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). Intradermal administration of HMWH does not attenuate the hyperalgesia induced by oxaliplatin in PI3Kγ antisense-treated rats (F(7,35)= 103.47, ****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). Four days after the 1st dose of paclitaxel, rats were treated with an oligodeoxynucleotide (ODN) antisense or mismatch (120 μg/ 20 μL, i.t.) against PI3Kγ mRNA, daily for 3 consecutive days. On day 7, approximately 24 h after the last injection of ODN, and paclitaxel, HMWH (1 μg/ 5 μL, i.d.) was injected. Mechanical nociceptive threshold was evaluated on day 0 and days 4 and 7 after administration of oxaliplatin, and again 30 min after HMWH. Paclitaxel decreases mechanical nociceptive threshold (i.e., produces hyperalgesia), measured on day 4 (F(7,35)= 54.74, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test), in both PI3Kγ antisense- and mismatch-treated groups. However, HMWH does not attenuate the hyperalgesia induced by paclitaxel in PI3Kγ antisense-treated rats (F(7,35)= 54.74, ****p<0.0001; two-way ANOVA followed by Bonferroni’s post hoc comparisons test). n= 6 per group.