Fig. 4

Rimegepant Intervention during the Modelling Period Slowed the Decline in the Pain Threshold. A Experimental flowchart for behavioural testing. B Temporal progression of mechanical allodynia thresholds in the head and hind paw of AI-MOHM mice following rimegepant intervention during modelling. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 RIZ + NTG + Gepant vs. RIZ + NTG + VEH. n = 12 in the RIZ + NTG + Gepant group and n = 15 in the RIZ + NTG + VEH group. C-D Comparative behavioural profiling in the EPM (C) and movement trajectory heatmaps (D) between prophylactically rimegepant-treated and control cohorts at the modelling endpoint. Heatmap gradients reflect spatial dwelling durations (spectral range: deep blue [minimum] to bright yellow [maximum]). Structural annotations: thin borders, open arms. thick borders, closed arms. n = 10 per group. E–F Open field behavioural analysis (E) and locomotion heatmaps (F) after prophylactic rimegepant administration. Thermal encoding indicates the residence time distribution (spectral range: deep blue to bright yellow). Spatial demarcations: inner quadrant, central zone; outer area between inner/outer quadrants, peripheral annular region. RIZ + NTG + Gepant group: n = 6; RIZ + NTG + VEH group: n = 5. G Dual immunofluorescence visualization of c-Fos/NeuN colocalization in the PrL (prelimbic cortex), IC (insular cortex), and SPVC (spinal trigeminal nucleus caudal subnucleus) following rimegepant intervention. Red: c-Fos; green: NeuN; white arrowheads: co-labelled neurons. The dashed white contours indicate anatomical boundaries; scale bar: 40 µm. H. Quantitative analysis of c-Fos + neuronal density in specified brain regions. n = 3 or 4 mice per group. ****p < 0.0001 RIZ + NTG + Gepant group vs. RIZ + NTG + VEH group