# LIGHT and Lymphotoxin targeting for the treatment of chronic orofacial pain conditions

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $231,000

## Abstract

Orofacial chronic pain mismanagement substantially contributes to opioid overuse, overdose related deaths
and cardiovascular, renal and neurological complications at epidemic proportions. To combat this problem, it
is necessary to elucidate a critical gap in knowledge by identifying and vigorously validating novel therapeutic
targets controlling the development and maintenance of chronic orofacial pain. The current paradigm implies
that orofacial conditions, such as temporomandibular joint and muscle disorders (TMJD) and oral cancer,
could trigger maladaptation of the immune system and cell plasticity supporting persistent inflammation,
which influences the development and maintenance of orofacial chronic pain. LIGHT (TNFSF14) and
Lymphotoxin-beta (LTβ), members of the tumor necrosis factor superfamily, are critical components
controlling a delicate balance between protective immunity and immunopathology during chronic
inflammatory diseases. The objectives of this proposal are: first, to rigorously validate whether local blockade
of LIGHT and LTβ signaling via LTβ receptor (LTβR) or Herpes Virus Entry Mediator (HVEM; TNFRSF14)
prevent the development and/or inhibit maintenance of chronic pain in several models of TMJD and oral
cancer; and second, to identify LIGHT and LTβ signaling-induced plasticity of immune, stromal and tumor
cells in masseter muscle and tongue, as well as of sensory neurons in trigeminal ganglia (TG), leading to
orofacial chronic pain. Based on the existing literature and our preliminary data, our central hypothesis is that
targeting LIGHT and LTβ signaling will prevent the development and inhibit maintenance of chronic
pain produced by TMJD and oral cancer via peripheral mechanisms involving plasticity of immune,
stromal and tumor cells as well as sensory neurons. Our hypothesis will be tested by three relevant yet
independent aims. Aim 1 validates whether local LIGHT and LTβ inhibition in masseter muscle prevents the
development and blocks maintenance of chronic pain in TMJD models. Aim 2 defines contribution of LIGHT
and LTβ to immune, stromal and neuronal cell plasticity during TMJD. Aim 3 determines whether LIGHT and
LTβ signaling contribute to the development and maintenance of chronic pain in oral cancer models via
regulation of cell plasticity in tongue. The proposed study is innovative because it validates novel targets to
facilitate the development of orofacial chronic pain therapeutics; and proposes conceptually novel peripheral
regulatory mechanisms involving LIGHT and LTβ signaling that control the development and maintenance of
TMJD and oral cancer chronic pain. The proposed research is significant as it advances our understanding
of mechanisms regulating the development and maintenance of orofacial pain; and offers targets and an
immunotherapeutic approach for preventing and blocking chronic pain during TMJD and oral cancer.

## Key facts

- **NIH application ID:** 10221292
- **Project number:** 3R01DE029187-01S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** ARMEN N AKOPIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 3
- **Project period:** 2019-09-20 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221292

## Citation

> US National Institutes of Health, RePORTER application 10221292, LIGHT and Lymphotoxin targeting for the treatment of chronic orofacial pain conditions (3R01DE029187-01S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10221292. Licensed CC0.

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