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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Pain. 2021 Mar 1;162(3):907–918. doi: 10.1097/j.pain.0000000000002073

Figure 5. Effect of chronic administration of stress hormones and unpredictable sound stress on oxaliplatin-induced hyperalgesia.

Figure 5.

Male and female rats were submitted to stress levels of epinephrine (osmotic minipumps filled with 5.4 μg/0.25 μL/h of epinephrine), corticosterone (100 mg in pellets), or their combination or exposed to unpredictable sound stress on days 1, 3, and 4. Stress hormone exposure protocol: (A and B): surgery for the implantation of epinephrine-containing osmotic minipumps or corticosterone fused pellets in the interscapular space was performed 24h before intravenous administration of oxaliplatin (2 mg/kg) (day 0). (A) In male rats, exposed to epinephrine or the combination of epinephrine and corticosterone, the magnitude of oxaliplatin-induced hyperalgesia was increased in both phases of oxaliplatin CIPN. Rats exposed to corticosterone alone, exhibited an increase in the magnitude of oxaliplatin-induced hyperalgesia at 30 min and 1 (early phase) and 21 (late phase) days after oxaliplatin administration. Data shown as mean ± SEM Treatment F (3,120) = 86.39; Time (5, 120) = 13.42; Interaction (15, 120) =1.221, ****P<0,0001: epinephrine or epinephrine +corticosterone vs oxaliplatin; **P<0,01, *P<0,05: epinephrine+ corticosterone vs oxaliplatin; ####P<0,0001, #P<0,05: corticosterone vs oxaliplatin, using two-way repeated measures ANOVA followed by Bonferroni post hoc test (n=6 paws per group). (B) When female rats were exposed to corticosterone alone or the combination of corticosterone and epinephrine, an increase in the magnitude of oxaliplatin-induced hyperalgesia was observed. The magnitude of oxaliplatin-induced hyperalgesia was not affected by epinephrine exposure. Data shown as mean ± SEM Treatment F (3,120) = 51.27; Time (5, 120) = 3.397; Interaction (15, 120) =1.007, ####P<0,0001, ##P<0,01: corticosterone vs oxaliplatin or corticosterone plus epinephrine vs oxaliplatin; #P<0,05: corticosterone plus epinephrine vs oxaliplatin, using two-way repeated measures ANOVA followed by Bonferroni post hoc test (n=6 paws per group). For the sound stress protocol (C and D): oxaliplatin (2 mg/kg, i.v.) was administered (day 0) 14 days after the last exposure to sound stress. Mechanical nociceptive threshold was evaluated before and again 30 min and 1, 7, 14, 21 and 28 days after oxaliplatin. (C) In male rats exposed to sound stress, the magnitude of oxaliplatin-induced hyperalgesia was increased at 30 min and 1, 7, 14 and 21 days after oxaliplatin administration. Data shown as mean ± SEM, Treatment F (1,48) = 81, Time F (5,48) = 18.05, Interaction (5,48) = 6.293, ****P<0,0001, ***P<0,001, **P<0,001: sound stress oxaliplatin vs sham stress oxaliplatin, (n=6 paws per group), using two-way repeated measures ANOVA followed by Bonferroni post hoc tests (n=6 paws per group). (D) The magnitude of oxaliplatin-induced hyperalgesia was increased in female rats exposed to sound stress at 30 min and 1, 7 and 14 days after oxaliplatin administration. Data shown as mean ± SEM, Treatment F (1,60) = 20.6, Time F (5,60) = 15.71, Interaction (5,60) = 2.367, *P<0,05: sound stress oxaliplatin vs sham stress oxaliplatin, using two-way repeated measures ANOVA followed by Bonferroni post hoc tests (n=6 paws per group).