(PR045) Neurogenic Inflammation in the Dental Pulp - An In-Vivo Study

Objective: Dental pulp, densely innervated tissue, can experience intense pain during procedures like crown preparations from sensory neuron activation, even before bacterial invasion, potentially necessitating root canal treatment. This study investigates whether sensory neuron activation can lead to local inflammatory changes in the pulp without bacterial presence. Noxious cold stimulation was applied unilaterally to the enamel of maxillary and mandibular molars of C57BL/6 WT mice using cold test spray (-20°C) on cotton to activate pulp sensory neurons. The procedure involved 20 repetitions per session, conducted twice daily over three days. Contralateral teeth served as controls. Sensory activation was assessed by quantifying c-Fos immunoreactive neurons in ipsilateral and contralateral sections of the trigeminal nucleus using immunohistochemistry. Pro-inflammatory cytokines were measured using multiplex ELISA. Innate immune cell changes were analyzed using flow cytometry. Statistical analyses included unpaired t-tests and two-way ANOVA with Tukey’s multiple comparisons.

Results: Cold stimulation significantly increased c-Fos expression in the ipsilateral trigeminal nuclei’s caudalis and interpolaris sections compared to the contralateral side (p=0.024). In cold-stimulated teeth dental pulp, there was no marked increase in cell death (p=0.17), but IL-6 concentrations were elevated (p=0.04), along with an increase in non-macrophage myeloid cells (CD11b+ F4/80-) (p < 0.0001), all compared to controls.

Conclusion: Noxious cold stimulation led to neuron activation in dental pulp, promoting inflammatory responses and changes in immune cell composition, without direct tissue damage. This study highlights that neuronal activation alone can drive pulp inflammation. Further work is required to understand if these changes are transient or persistent.