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. 2020 Jul 21;162(1):263–274. doi: 10.1097/j.pain.0000000000002014

Figure 2.

Figure 2.

Microinjections of DAPT into the ACC relieved CCI-induced neuropathic pain in a dose-dependent manner. (A) Schematic of the early ACC microinjection experiments. (B) Representative rat section through the ACC, 1.7 mm rostral to the bregma. (C) The NICD level was significantly decreased 7 days after CCI in the DAPT group compared to the Vehicle group (P < 0.001***, Student t-test, n = 8 samples per group). (D) There were no differences in NICD level between DAPT and Vehicle groups 14 days after CCI. (E) Two-way repeated-measures ANOVA indicated a significant effect of the interaction of DAPT (CCI + DAPT vs CCI + Vehicle) and time (day −1 to 28) on the mechanical allodynia induced by the intra-ACC microinjection of DAPT (50 μg and 2 μL each side) (F = 3.926, P < 0.001***, n = 8 animals per group, two-way ANOVA). A post hoc test (Bonferroni) revealed that the microinjection of DAPT reversed the mechanical allodynia of CCI rats compared to the Vehicle (black: CCI + Vehicle, red: CCI + DAPT). (F) Attenuation of CCI-induced thermal hyperalgesia by the intra-ACC microinjection of DAPT (F = 3.536, P = 0.0018**, n = 8 animals per group, two-way ANOVA followed by the Bonferroni post hoc test, black: CCI + Vehicle, red: CCI + DAPT). (G) Reversal of mechanical allodynia after CCI by microinjections of different doses of DAPT; only 50 μg and 100 μg significantly reversed the paw withdrawal threshold (F = 2.098, P = 0.0044**, n = 8 animals per group, two-way ANOVA followed by the Bonferroni post hoc test, black: CCI + Vehicle, red: CCI + DAPT 20 μg, green: CCI + DAPT 50 μg, blue: CCI + DAPT 100 μg). (H) Microinjections of different doses of DAPT into the ACC increased the paw withdrawal latency (F = 2.875, P < 0.0001***, n = 8 animals per group, two-way ANOVA followed by the Bonferroni post hoc test, black: CCI + Vehicle, red: CCI + DAPT 20 μg, green: CCI + DAPT 50 μg, blue: CCI + DAPT 100 μg). ACC, anterior cingulate cortex; ANOVA, analysis of variance; CCI, chronic constriction injury; DAPT, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester; NICD, Notch intracellular domain.