# Trigeminal Afferents Regulation of Apical Periodontitis Development

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $362,188

## Abstract

Project Summary
Apical periodontitis (AP) is a highly prevalent and debilitating pathological condition marked by
bone resorption and pain as result of dental infections. Many elegant studies have revealed the
functions of immune cells and inflammatory mediators in AP. Despite AP being densely
innervated by trigeminal ganglia (TG) fibers, the participation of these afferents in this disease
process is largely unknown. Our preliminary data demonstrate that TG neurons regulate AP
lesion development. The objective of this proposal is to understand how TG fibers control AP
development, which remains a large gap in knowledge. We, for the first time, propose to
investigate neurons/non-neuronal cell interaction in control of AP development for each of four
major subclasses of TG neurons. This is novel and critically important strategy in approaching
research on regulation of AP development by sensory neurons, since each neuronal sub-class
has distinct function and biochemical make up, including unique sets of receptors, ion channels
and neuropeptides. Hence, it is possible that regulatory potential of TG neuronal subsets could
dramatically vary; and even produce opposite effects on osteoclasts and osteoblasts. So
according to literature and preliminary experiments, we designed a novel strategy on study AP
development by TG neurons. Our central hypothesis is that in response to infection certain
subclasses of TG afferents inhibit bone resorption in apical periodontitis via the regulation of
osteoclastic and osteoblastic activities. This hypothesis will be tested in: Aim 1 examining role
of different subclasses of TG afferents in inhibiting bone resorption and immunological
responses in a murine model of infection-induced AP; Aim 2 defining involvement of different
subclasses of TG neurons on regulation of osteoclastic and osteoblastic functions; and Aim 3
defining and identifying the released soluble factor(s) from different subclasses of TG neurons
and their contribution to modulation of osteoclast and osteoblast functions. We believe that
knowledge generated by this application will have a substantial positive impact from both
scientific and clinical perspectives. Scientifically, this is the principally novel approach in
investigation of AP using subclass-specific TG mouse lines. Moreover, the generated new
insight into interactions between neurons and DCS remodeling will open pathways for further
scientific advancement. Clinically, identification of neuronal regulatory mechanisms could offer
novel strategies and, importantly, targets for developing anti-AP therapeutics.

## Key facts

- **NIH application ID:** 10208856
- **Project number:** 5R01DE027929-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Anibal Diogenes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $362,188
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208856

## Citation

> US National Institutes of Health, RePORTER application 10208856, Trigeminal Afferents Regulation of Apical Periodontitis Development (5R01DE027929-04). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10208856. Licensed CC0.

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