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Fig. 5 | Journal of Translational Medicine

Fig. 5

From: The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling

Fig. 5

A TSPO antagonist attenuated the antidepressant and analgesic effects of TPPU. A Schedule of the experiment. SNI surgery was performed on day 0 after acclimation. Finasteride (10 mg/kg, once daily) or PK-11195 (3 mg/kg, once daily) was administered orally together with TPPU (3 mg/kg, once daily) for 7 consecutive days, starting at day 14 after SNI. AC-5216 (5 mg/mg) was administered orally from day 14 to day 21. MWT was measured on days 7, 14, 15, 16, 17, 18, 19, 20, and 21 after SNI. The SPT was performed on days 5, 12, and 21 after SNI. B Dendrogram of the hierarchical clustering analysis. A total of 36 SNI mice were classified into anhedonia-susceptible and anhedonia-resilient groups based on SPT scores. C MWT [Time: F (9, 63) = 73.44, P < 0.001; Group: F (5, 35) = 156.5, P < 0.001; Interaction: F (45, 315) = 9.604, P < 0.001] was measured on days 7, 14, 15, 16, 17, 18, 19, 20, and 21 after SNI in the Sham, Sus, Sus + TPPU, Sus + Fina + TPPU, Sus + PK + TPPU, and Sus + AC groups. ***P < 0.001, Sus group vs. Sus + AC group; ###P < 0.001, Sus group vs. Sus + TPPU group. D The SPT [F(5, 42) = 18.98, P < 0.001] was performed on day 21 after SNI in the Sham, Sus, Sus + TPPU, Sus + Fina + TPPU, Sus + PK + TPPU, and Sus + AC groups. ***P < 0.001. E CYP1A1 level in the serum [F (5, 42) = 3.299, P < 0.05]. F CYP1B1 level in the serum [F (5, 42) = 1.825, P = 0.13]. G IL-1β level in the serum [F (5, 42) = 4.101; P < 0.01]. H TNF-α level in the serum [F (5, 42) = 3.41; P < 0.05]. *P < 0.05, **P < 0.01, ***P < 0.001. AC AC-5216, AHR aryl hydrocarbon receptor, CYP1A1 cytochrome P450, family 1, subfamily A, polypeptide 1, CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1; Fina, finasteride, NS not significant, SNI spared nerve injury; Sus, susceptible, TPPU 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, PK PK-11195

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