Neuronal-immune Axis Alters Pain and Sensory Afferent Damage During Dental Pulp Injury

Abstract

Dental pulp tissue is densely innervated by afferent fibers of the trigeminal ganglion. When bacteria cause dental decay near the pulpal tissue, a strong neuronal and immune response occur, creating pulpitis, which is associated with severe pain and pulp tissue damage. Neuro-immune interactions have the potential to modulate both the pain and pathological outcome of pulpitis. We first investigated the role of the neuropeptide calcitonin-gene related peptide (CGRP), released from peptidergic sensory afferents, in dental pain and immune responses by using calca knock out (calca-/-) and wild type (calca+/+) mice, in a model of pulpitis by creating a mechanical exposure of the dental pulp horn. While CGRP did not contribute to facial mechanical hypersensitivity, at an early time point, it did contribute to spontaneous pain-like behavior. We also found that CGRP contributed to recruitment of neutrophils and monocytes, while not clearly affecting the progression of pulpal pathology histologically. When we depleted neutrophils and monocytes, we found that there was more sensory afferent loss, tissue damage and deeper spread of bacteria into the pulp tissue, while there was a reduction in facial mechanical hypersensitivity compared to control animals at a later time point. Overall, we showed that there is a crosstalk between peptidergic neurons and neutrophils in the pulp, modulating the pain and inflammatory outcomes of the disease.