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. 2016 Oct 14;7:13102. doi: 10.1038/ncomms13102

Figure 3. Glucocorticoids decrease the threshold of mechanical allodynia in PSL mice via P2Y12 receptor in the ipsilateral spinal cord.

Figure 3

(a) Diurnal oscillations in ATP release from spinal slices were abrogated by adrenalectomy (means±s.e.m.; n=5–6). Significant time-dependent variations are observed in ATP release from the ipsilateral (Ipsi.) (F5,30=2.552, P=0.035; ANOVA) and contralateral (Contra.) sides (F5,30=2.049, P=0.048; ANOVA). (b) Subcutaneous (s.c.) administration of CORT (30 mg kg−1) to male ADX+PSL mice enhances ATP release from spinal slices (means±s.e.m.; n=5). *P<0.05 significantly different from the basal level (F3,16=3.755, P=0.042 for Ipsi.; F3,16=4.933, P=0.018 for Contra.; ANOVA with Tukey–Kramer's PHT). (c) Administration of CORT (30 mg kg−1, s.c.) to male ADX+PSL mice decreases the withdrawal threshold of the ipsilateral hindpaw (means±s.e.m.; n=6). **P<0.01; *P<0.05 significantly different from the basal level (F6,35=2.356, P=0.042; ANOVA with Tukey–Kramer's PHT). (d) Intrathecal (i.th.) injection of ATP (30 nmol per mouse) to male ADX+PSL mice decrease the withdrawal threshold of the ipsilateral hindpaw (means±s.e.m.; n=8). **P<0.01; *P<0.05 significantly different from the basal level (F6,49=3.964, P=0.002; ANOVA with Tukey–Kramer's PHT). (e) The P2Y12 receptor antagonists AR-C69931 (5 pmol per mouse, i.th.) or AZD6140 (10 pmol per mouse, i.th.) prevent CORT (30 mg kg−1, s.c.)-induced pain hypersensitivity in male ADX+PSL mice (means±s.e.m.; n=5–6). *P<0.05; significantly different from other groups (F23,90=1.012, P=0.046; ANOVA with Tukey–Kramer's PHT). (f) Effects of antagonist P2X1–4 receptors TNP-ATP (3 nmol per mouse, i.th.) or antagonist P2Y6 receptor MRS2578 (30 nmol per mouse, i.th.) on CORT (30 mg kg−1, s.c.)-induced pain hypersensitivity in male ADX+PSL mice (means±s.e.m.; n=5–6). *P<0.05; significantly different from other groups (F23,93=1.987, P=0.014; ANOVA with Tukey–Kramer's PHT). (g) The withdrawal threshold of the ipsilateral hindpaw of male sham+PSL mice after the injection of AR-C69931 (5 pmol per mouse, i.th.) or AZD6140 (10 pmol per mouse, i.th.) (means±s.e.m.; n=5–6), **P<0.01, *P<0.05 significantly different from vehicle (0.01% DMSO, 0.01% ethanol in PBS)-treated groups (F14,75=1.965, P=0.033; ANOVA with Tukey–Kramer's PHT). Time of drug administration was set at ZT10. All experiments were performed on day 7 after nerve injury.