Abstract Background To quantify the expression of SP, CGRP, and VEGF in human dental pulps as a response to occlusal interferences, moderate orthodontic forces, and occlusal interferences plus moderate orthodontic forces simultaneously. Methods Forty human dental pulp samples were collected from healthy premolars indicated for extraction for orthodontic reasons. The teeth were divided into four groups with 10 samples each: Healthy pulp control group, occlusal interference group, moderate orthodontic forces group; and occlusal interferences plus moderate orthodontic forces group. Stimuli were applied for 24 h before tooth extraction in all experimental groups. All samples were processed, and SP, CGRP, and VEGF were measured by radioimmunoassay. The ANOVA test was performed to establish significant differences between groups and Tukey’s HSD post hoc comparisons were also performed. Results The highest increase in SP, CGRP, and VEGF expressions was found in the occlusal trauma plus orthodontic forces group, followed by the moderate orthodontic forces, the occlusal interferences and the control groups, with statistically significant differences between all groups (ANOVA p<0.001) and post-hoc comparisons (Tukey HSD p<0.001). Conclusion SP, CGRP, and VEGF expressions significantly increase in human dental pulps when stimulated by occlusal interferences combined with moderate orthodontic forces, as compared with when these two stimuli are applied independently. Peptides expression is directly proportional to the magnitude of the stimulus. Name of the registry: Importance of Neurogenic Inflammation in the Angiogenic Response of the Dental Pulp as a Defensive Response Trial registration number: NCT03804034 Date of registration: 01/15/2019 Retrospectively registered URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03804034?term=NCT03804034&draw=2&rank=1