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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 3. Role of β2-adrenergic receptor (ADRB2) in oxaliplatin-induced hyperalgesia.

Figure 3.

Male and female rats were treated with intrathecal injections of ODN AS or MM to ADRB2 mRNA, for 10 consecutive days (80 μg/day, 20 μl) in prevention (A and B) or reversal (C and D) protocols. Prevention protocol: oxaliplatin (2 mg/kg, i.v.) was administered approximately 17 hours after the third daily intrathecal injection of ADRB2 ODN (day 0). Mechanical nociceptive threshold was evaluated before ODN treatment was started and again on days 0 (30 min), 1, 7, 14, 21, and 28 days after oxaliplatin. (A) The magnitude of oxaliplatin-induced hyperalgesia was significantly attenuated in males treated with ADRB2 AS-ODN, when it was compared with the ADRB2 MM-ODN-treated group. Data shown as mean ± SEM, Treatment F (1,60) = 139.7, Time F (5, 60) = 2.634, Interaction F (5,60) = 8.180, ****P<0,0001, ***P<0,001: ADRB2 AS-ODN vs ADRB2 AS-MM (n=6 paws per group). (B) The magnitude of oxaliplatin-induced hyperalgesia was not affected by ADRB2 AS-ODN in the prevention protocol, in females. Data shown as mean ± SEM, Treatment F (1,60) = 6.620, Time F (5,60) = 2.452, Interaction F (5,60) = 1.498, ADRB2 AS-ODN vs ADRB2 AS-MM (n=6 paws per group). Reversal protocol: intrathecal treatment with ADRB2 AS- or MM-ODN started 3 days after intravenous administration of oxaliplatin (2 mg/kg). Mechanical nociceptive threshold was evaluated before oxaliplatin administration and again 30 min, 1, 7, 14, 21, and 28 days later (n=6 paws per group). (C) Oxaliplatin-induced hyperalgesia was significantly reversed in males treated with ADRB2 AS-ODN, when compared with the ADRB2 MM-ODN-treated group. Data shown as means ± SEM, Treatment F (1,60) =33.76, Time (5,60) = 2.318, Interaction F (5,60) = 4.256, ****P<0,0001, ***P<0,001, **P<0,01: ADRB2 AS-ODN vs ADRB2 AS-MM (n=6 paws per group). (D) The magnitude of oxaliplatin-induced hyperalgesia was not affected by ADRB2 AS-ODN in the reversal protocol, in females. Data shown as means ± SEM, Treatment F (1,60) = 6.293, Time (5,60) = 8.433, Interaction F (5,60) = 0.1567 (n=6 paws per group). Two-way repeated measures ANOVA followed by Bonferroni post hoc tests were used to compare antisense and mismatch groups over time.