Fig. 1

Overuse of RIZ Enhances Potential Nociceptive Sensitization Induced by Repeated NTG Interventions A. Experimental flowchart for behavioural testing. RIZ: rizatriptan. NS: normal saline. NTG: nitroglycerin. i.p.: intraperitoneal injection. p.o.: peros. EPM: elevated plus maze. OFT: open field test. B Comparison of trends in hind paw mechanical pain thresholds over time during modelling and during withdrawal among the four groups (left). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, NS + DDW group vs. NTG + RIZ group. $p < 0.05, $$p < 0.01, $$$p < 0.001, $$$$p < 0.0001 NS + DDW group vs. NTG + DDW group. &p < 0.05 NS + RIZ group vs. NTG + DDW group. ^p < 0.05, ^^p < 0.01, ^^^p < 0.001, ^^^^p < 0.0001 NS + DDW group vs. NS + RIZ group. @ p < 0.05, @@p < 0.01 NS + RIZ group vs. NTG + RIZ group. Comparison of trends in head mechanical pain thresholds over time during modelling and during withdrawal among the four groups (right). * p < 0.05, **p < 0.01 NS + DDW group vs. NTG + RIZ group. $p < 0.05, $$p < 0.01 NS + DDW group vs. NTG + DDW group. &p < 0.05 NS + RIZ group vs. NTG + DDW group. ^p < 0.05, ^^p < 0.01 NS + DDW group vs. NS + RIZ group. The data are presented as the means ± SEMs. n = 6 mice per group. C Changes in mechanical nociceptive thresholds in the head and hind paw regions over 5 h following SNP stimulation in the four groups of mice. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (NS + DDW vs. NTG + RIZ). @p < 0.05, @@p < 0.01 (NS + RIZ vs. NTG + RIZ). #p < 0.05, ##p < 0.01, ###p < 0.001 (NTG + DDW vs. NTG + RIZ). ^p < 0.05 (NS + DDW vs. NS + RIZ). The data are presented as the means ± SEMs. n = 6 mice per group. D Temporal progression of active feeding behavioural patterns in the four experimental cohorts during the model establishment phase. n = 6 mice per group. E Comparative behavioural analysis in the EPM test and movement trajectory heatmaps between the NTG + RIZ and NS + DDW groups post-modelling. The heatmap spectrum reflects the dwelling time distribution across spatial coordinates, ranging from deep blue (minimal duration) to bright yellow (maximal duration). Structural delineations: Thinner borders denote open arms, and thicker borders represent closed arms. The number of experimental animals per group was 18. F Open field behavioural comparison between the NTG + RIZ and NS + DDW groups post-modelling. The thermal gradient illustrates the spatial dwelling time from deep blue (lowest) to bright yellow (highest). The inner quadrant demarcates the central zone, with the annular region between the inner and outer quadrants defining the peripheral area. **p < 0.01, ***p < 0.001, ****p < 0.0001, NS + DDW group vs. NTG + RIZ group. n = 18 mice per group