Roles of neutrophil-sensory neuron interactions in dental pulp inflammation and pain

Pulpitis is a painful disease of the dental pulp, which is treated with expensive, invasive procedures such as root canal therapy and tooth extractions. A limited understanding of the intermingling mechanisms of inflammation and pain involving the innate immune response and the dense innervation of the pulp tissue jointly precludes the precise application of conservative treatments and the development of novel pain management strategies. In this project, the principal investigator will focus on the roles of neutrophils in nerve injury and pain during pulpitis, and how nociceptive neurons modulate innate immune response. Moreover, she proposes to study neuro-immune interactions during pulpitis not only limited within the pulp tissue but in the pulp-periodontium complex where these two neighboring tissues are neuroanatomically connected. The central hypothesis of the study is that during pulpitis, inflammation is present in the pulp and also in the periodontium, and it is modulated by nociceptive neurons, and driven by neutrophils which regulate sensory and pain outcomes. In Aim 1 will identify neutrophil-driven nerve injury and pain outcomes during pulpitis by using different clinically informed animal models of pulpitis, perform pharmacological manipulations of neutrophils, use tissue-clearing and whole-mount imaging, single-nuclei RNA sequencing and in-situ hybridization to detect anatomical and transcriptional changes of neurons. She will also use evoked and non-evoked pain behavior assays. Aim 2 will identify the impact of nociceptive neurons on neutrophil recruitment and responses in the pulp tissue during pulpitis. She will use chemogenetic DREADD-based approaches to silence certain subsets of neurons and perform flow cytometry and sensitive ELISA-based assays to assess innate immune responses. Aim 3 will identify the mechanisms and unique signatures of inflammation in the neighboring periodontium during pulpitis, focusing on neuronal-driven inflammation, by using in vivo dental pulp neuron activation models and pulpitis models. She will investigate neurogenic inflammatory mechanisms, outcomes, and establish the framework and understanding of how the neighboring periodontium anticipates and responds to diseases affecting the pulp tissue. Investigation of these proposed goals will guide biologically based, less interventional treatments and pain management strategies, and establish an understanding for the development of accurate biologically based diagnostic approaches for pulpitis. Project Number: 4R00DE033421-03 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Ozge Erdogan | Institution: BOSTON UNIVERSITY MEDICAL CAMPUS, BOSTON, MA | Award Amount: $249,000 | Activity Code: R00 | Study Section: NSS View on NIH RePORTER: https://reporter.nih.gov/project-details/11482326