# Identifying the Role of the Periaqueductal Gray in Mediating Traumatic Brain Injury Induced Thermal and Mechanical Hypersensitivity Reduction After Green Light Exposure

> **NIH VA I01** · SOUTHERN ARIZONA VA HEALTH CARE SYSTEM · 2024 · —

## Abstract

Mild traumatic brain injury (mTBI) is the most common traumatic brain injury affecting military personnel. mTBI
is associated with several neurological symptoms that correlate with neuroinflammation. One of the neurological
symptoms associated with mTBI is pain. mTBI-induced pain may be challenging to manage in some cases.
Therefore, opioids may be used to control such pain. However, opioids have significant side effects, especially
when used chronically, which may lead to substance misuse. The opioid crisis has demonstrated the need for
complementary methods for pain control. Because of the association between mTBI and substance misuse,
there is a significant need for alternative/complementary approaches to opioids to treat pain, especially in treating
the pain associated with mTBI.
mTBI induces inflammation as manifested by increased inflammatory cytokines such as IL-6 and TNF-α in the
central nervous system (CNS) and plasma. Two sources for these cytokines are microglia and astrocytes, both
of which become activated after mTBI, contributing to the development of pain. Decreasing the levels of pro-
inflammatory cytokines and increasing the levels of anti-inflammatory cytokines may promote decreased mTBI-
induced pain. A therapy that reduces microglia and astrocytes' activation and decreases the neuroinflammatory
environment would be ideal for both military personnel and veterans.
Phototherapy is used for multiple medical conditions, but few studies investigated the effects of phototherapy on
pain. We have shown that green light exposure (GLED) was antinociceptive by reversing thermal and mechanical
hypersensitivity in rats. In humans, we have demonstrated that GLED decreased chronic pain and sleep
disturbances in fibromyalgia and migraine, suggesting that GLED therapy applies to humans despite differences
in the visual systems between rodents and humans. Furthermore, we have shown that GLED reversed the
hypersensitivity associated with mTBI in two different TBI mice models. We also demonstrated that GLED
reversed postsurgical thermal and mechanical hypersensitivity by increasing anti-inflammatory IL-10 levels in
the cerebrospinal fluid (CSF) while decreasing pro-inflammatory IL-6. GLED reversal of thermal and mechanical
hypersensitivities was attenuated when the periaqueductal gray (PAG), a crucial pain-modulating center, was
blocked, suggesting that GLED may be inhibiting the descending pain-facilitatory pathway.
Therefore, it is reasonable to postulate our hypothesis that GLED visual exposure will attenuate mTBI-
induced hypersensitivity by inhibiting the descending pain-facilitatory pathway.
We will use three specific aims (SA) to investigate our hypothesis. SA1 will explore the potential translation of
GLED therapy by exploring its ability to reverse the mTBI-induced thermal and mechanical hypersensitivities in
multiple rodent sexes and species. SA2 will evaluate the effects of GLED on modulating glial cells and the effects
on neuroinflamma...

## Key facts

- **NIH application ID:** 10700314
- **Project number:** 1I01BX005965-01A1
- **Recipient organization:** SOUTHERN ARIZONA VA HEALTH CARE SYSTEM
- **Principal Investigator:** Mohab M Ibrahim
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700314

## Citation

> US National Institutes of Health, RePORTER application 10700314, Identifying the Role of the Periaqueductal Gray in Mediating Traumatic Brain Injury Induced Thermal and Mechanical Hypersensitivity Reduction After Green Light Exposure (1I01BX005965-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10700314. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*