Fig 2: Oral cancer-induced changes in pain-related protein expression. Each TG tissue sections from each retrogradely labeled mouse was stained with antibodies specific for either TRPV1, CGRP or ATF3. Representative immunostaining of all three markers in retrogradely labeled TG tissue from (A) sham and MOC1 mice at PID40 as well as (B) sham and MOC2 mice at PID14. (C,D) The percentage of DiI-labeled neurons expressing each marker was quantified from 2–4 animals per treatment group. Data are presented as mean +/- SEM of percentage of neurons expressing each marker. Two-way ANOVA, Treatment effect: *p < 0.05, **p < 0.01, sex effect: #p < 0.05.

Fig 3: CGRP increased the wound healing ability of OSCC cells in vitro through itsreceptor calcitonin receptor like receptor (CLR). A CGRP increased the wound healing capacity of OSCC cells, and blockade of CGRP receptor using CLR inhibitor Rimegepant antagonized the effects of CGRP in both HN6 and Cal27 cells. B Knockdown of the CGRP receptor using small interfering RNA antagonized the effects of CGRP in both HN6 and Cal27 cells

Fig 4: Both ROS and the TRPA1 activation reversed the inhibitory effects of the anti-CGRP antibody on CSD in the mouse brain slice. CSD was induced by 260 mM KCl. There were four groups: anti-IgG antibody at 0.025 µM (i, n = 6) as the control, anti-CGRP antibody at 0.4 µM in the absence (ii, n = 6) or presence of 50 µM of the TRPA1 agonist, AITC (iii, n = 6) or the ROS activator, H2O2 (vi, n = 6). In order to minimize the animal use, data in anti-IgG antibody control group and the anti-CGRP antibody were adopted and transformed from that in Fig. 5 in our recent paper [5]. Representative trace of the 2nd CSD episode in each group are shown in the panel a. The data showed that both ROS and the TRPA1 activation reversed the prolonged CSD latency (b), but not magnitude (c) under the perfusion of the anti-CGRP antibody. Data were plotted as percentage of their initial levels (1st CSD episode) and indicated as median (range). Mann-Whitney U test, one-tailed, was used for significant analysis between two independent groups. *p < 0.05, **p < 0.01. Abbreviation: Ab indicates antibody

Fig 5: Schematic illustration of this study.PRAT afferent nerves serve as a pathological node of hypertension that sustains high BP via suppressing CGRP, thereby being a potential therapeutic target to tackle primary hypertension.