ABSTRACTObjective:To determine the levels of two sensory neuropeptides (substance P [SP] and calcitonin gene-related peptide [CGRP]) and two endogenous opioids (methionine-enkephalin [Met-Enk] and β-endorphin [β-End]) in dental pulp tissue samples subjected to controlled orthodontic intrusive forces.Materials and Methods:Sixteen healthy premolars were selected from eight patients who were undergoing extraction for orthodontic purposes. Eight were randomly used as controls, and the other eight were assigned to an experimental group (controlled orthodontic intrusive forces applied for 24 hours). After this period, teeth were extracted, and pulp samples were obtained. All samples were processed to quantify the expression levels of SP, CGRP, Met-Enk, and β-End using commercial radioimmunoassay kits.Results:All samples exhibited basal levels of both neuropeptides and endogenous opioids. After 24 hours of the intrusive stimulus, all patients reported a tolerable discomfort localized at the involved premolar. Only SP was significantly increased (P < .05). For the other molecules, no statistically significant differences were observed (P > .05); however, they expressed important increasing trends.Conclusions:The expression levels of SP and CGRP in dental pulp samples from the experimental group support the positive correlation between the symptomatic clinical scenario and increased expression levels of neuropeptides, clarifying the role of neurogenic inflammation in early injury response.