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ORIGINAL RESEARCH

MiR-204-5p Alleviates Neuropathic Pain by Targeting BRD4 in a Rat Chronic Constrictive Injury Model

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Pages 2427-2435 | Received 20 Apr 2022, Accepted 08 Aug 2022, Published online: 18 Aug 2022

Figures & data

Figure 1 Effects of CCI on inflammatory response, stimulation of mechanical pain and thermal pain in rats. (A) The mechanical pain threshold was decreased in the CCI group. (B) The thermal pain threshold was decreased in the CCI group. The level of (C) IL-6 and (D) TNF-α in the CCI group was increased. Unpaired t-test and one-way repeated measures ANOVA. ***P < 0.001 vs sham group.

Figure 1 Effects of CCI on inflammatory response, stimulation of mechanical pain and thermal pain in rats. (A) The mechanical pain threshold was decreased in the CCI group. (B) The thermal pain threshold was decreased in the CCI group. The level of (C) IL-6 and (D) TNF-α in the CCI group was increased. Unpaired t-test and one-way repeated measures ANOVA. ***P < 0.001 vs sham group.

Figure 2 MiR-204-5p level was down-regulated in chronic constriction injury (CCI) rat model. One-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001 vs sham group.

Figure 2 MiR-204-5p level was down-regulated in chronic constriction injury (CCI) rat model. One-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001 vs sham group.

Figure 3 Effects of miR-204-5p on inflammatory response, stimulation of mechanical pain and thermal pain in CCI rat model. (A) LV- miR-204-5p injection can up-regulate miR-204-5p level in the CCI group. Injection of LV-miR-204-5p alleviated (B) mechanical pain stimulation and (C) thermal pain stimulation in CCI rats. Injection of LV-miR-204-5p inhibited (D) IL-6 and (E) TNF-α levels in CCI rats. One-way repeated measures ANOVA. ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group.

Figure 3 Effects of miR-204-5p on inflammatory response, stimulation of mechanical pain and thermal pain in CCI rat model. (A) LV- miR-204-5p injection can up-regulate miR-204-5p level in the CCI group. Injection of LV-miR-204-5p alleviated (B) mechanical pain stimulation and (C) thermal pain stimulation in CCI rats. Injection of LV-miR-204-5p inhibited (D) IL-6 and (E) TNF-α levels in CCI rats. One-way repeated measures ANOVA. ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group.

Figure 4 BRD4 is a potential target gene of miR-204-5p. (A) Complementary binding sites of miR-204-5p and BRD4. (B) The luciferase reporter gene proved that miR-204-5p binds to BRD4. ***P < 0.001 vs Control group. (C) BRD4 level was upregulated in CCI rat model. (D) Overexpression of miR-204-5p can inhibit the level of BRD4. Unpaired t-test and one-way repeated measures ANOVA. *P < 0.05, ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group.

Figure 4 BRD4 is a potential target gene of miR-204-5p. (A) Complementary binding sites of miR-204-5p and BRD4. (B) The luciferase reporter gene proved that miR-204-5p binds to BRD4. ***P < 0.001 vs Control group. (C) BRD4 level was upregulated in CCI rat model. (D) Overexpression of miR-204-5p can inhibit the level of BRD4. Unpaired t-test and one-way repeated measures ANOVA. *P < 0.05, ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group.

Figure 5 Effects of BRD4 on inflammatory response, stimulation of mechanical pain and thermal pain in CCI rat model. (A) The addition of BRD4 can reverse the inhibitory effect of miR-204-5p on BRD4 expression. Overexpression of BRD4 aggravated (B) mechanical pain stimulation and (C) thermal pain stimulation in CCI rats. Overexpression of BRD4 promoted (D) IL-6 and (E) TNF-α levels in CCI rats. One-way repeated measures ANOVA. ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group. &&P < 0.01, &&&P < 0.001 vs CCI + LV-miR-204-5p group.

Figure 5 Effects of BRD4 on inflammatory response, stimulation of mechanical pain and thermal pain in CCI rat model. (A) The addition of BRD4 can reverse the inhibitory effect of miR-204-5p on BRD4 expression. Overexpression of BRD4 aggravated (B) mechanical pain stimulation and (C) thermal pain stimulation in CCI rats. Overexpression of BRD4 promoted (D) IL-6 and (E) TNF-α levels in CCI rats. One-way repeated measures ANOVA. ***P < 0.001 vs sham group, ###P < 0.001 vs CCI group. &&P < 0.01, &&&P < 0.001 vs CCI + LV-miR-204-5p group.