Low-Level Laser Therapy Reduces Pain-Signaling Neuropeptides CGRP and Substance P After Facial Nerve Injury | Research

The takeaway

Low-level laser therapy decreased expression of the pain neuropeptides substance P and CGRP in the trigeminal ganglion after nerve injury in rats, suggesting a molecular mechanism for laser-based pain relief.

CGRP and substance P both decreased
Low-level laser therapy reduced expression of both major pain-signaling neuropeptides — CGRP and substance P — in the trigeminal ganglion after nerve injury, providing a molecular mechanism for laser-based facial pain relief.

What the researchers found

In rats with inferior alveolar nerve (IAN) injury:

- Nerve injury alone increased expression of TRPV1 (pain receptor) and substance P in the trigeminal ganglion, but did not change GluA1, GluA2 (AMPA receptors), or CGRP expression

- Low-level laser therapy (LLLT) produced multiple changes:

- Decreased TRPV1 expression (pain receptor)

- Decreased substance P expression (pain neuropeptide)

- Decreased CGRP expression (pain neuropeptide)

- Increased GluA1 and GluA2 expression (AMPA receptors)

The combined pattern suggests LLLT counteracts the molecular changes that drive pain sensitization after nerve injury.

Why it matters

Facial pain from nerve injury (trigeminal neuropathy) can be debilitating and difficult to treat with conventional medications. Understanding exactly how low-level laser therapy reduces pain at the molecular level — by decreasing CGRP and substance P — could help optimize LLLT protocols and validate it as a legitimate treatment option. It also highlights how neuropeptide modulation is central to pain management beyond traditional drug approaches.

How the study worked

Sprague-Dawley rats underwent inferior alveolar nerve injury surgery. Three groups were compared: naive (uninjured), injured without treatment, and injured with low-level laser therapy. Protein expression of GluA1, GluA2 (AMPA receptor subunits), CGRP, substance P, and TRPV1 was measured in trigeminal ganglion tissue and compared across groups.

What this study cannot tell us

This is an animal study using rats, and results may not directly translate to human facial pain conditions. The specific LLLT parameters (wavelength, power, duration) are not detailed in the abstract. Sample sizes per group are not specified. The study measured protein expression but did not directly assess pain behavior. The mechanism linking LLLT to neuropeptide changes is not fully explained. The 2017 publication date means newer LLLT protocols may differ.

How to read the evidence

This is a preclinical animal study using a rat model of nerve injury. While it provides valuable mechanistic data on neuropeptide changes, the findings are preliminary and have not been validated in human studies. Small sample sizes and lack of behavioral data further limit the evidence grade.

When this study was published

Published in 2017, this study is nearly a decade old. While the fundamental biology of CGRP and substance P in pain signaling remains relevant, newer research may have expanded on or refined these findings, particularly with advances in LLLT technology.

The bigger picture

CGRP and substance P are two of the most important neuropeptides in pain signaling. CGRP is already a major drug target — CGRP antagonists are FDA-approved for migraine treatment. This study shows that non-pharmacological interventions like laser therapy can also modulate these neuropeptide pathways, potentially offering a complementary or alternative approach to drug-based pain management. It also contributes to the broader understanding of how neuropeptides drive chronic pain after nerve injury.

Questions still open

Does low-level laser therapy reduce CGRP and substance P levels in human trigeminal pain conditions?
Could LLLT be combined with CGRP antagonists for enhanced pain relief in trigeminal neuropathy?
What LLLT parameters (wavelength, power, duration) produce the greatest reduction in pain neuropeptide expression?

Common questions

How does laser therapy reduce facial pain at the molecular level?

This study found that low-level laser therapy reduces the production of two key pain-signaling neuropeptides — CGRP and substance P — in the nerve center (trigeminal ganglion) responsible for facial sensation. When a facial nerve is injured, these neuropeptides increase and drive chronic pain sensitization. By reducing their levels, laser therapy may interrupt the molecular cascade that turns acute nerve injury into persistent pain.

What are CGRP and substance P?

CGRP (calcitonin gene-related peptide) and substance P are small signaling molecules (neuropeptides) released by nerve cells that amplify pain signals. CGRP has become a major drug target — medications that block it (like erenumab and rimegepant) are now FDA-approved for migraine prevention and treatment. Substance P is another pain-related neuropeptide that contributes to inflammation and sensitization. Both are elevated after nerve injury and contribute to chronic pain conditions.

Read the original research

Neurochemical effects of photobiostimulation in the trigeminal ganglion after inferior alveolar nerve injury.

Journal of biological regulators and homeostatic agents, 31(1), 147-152

View on PubMed ↗

Citation

Martins, D O; Santos, F M; Britto, L R G; Lemos, J B D; Chacur, M. (2017). Neurochemical effects of photobiostimulation in the trigeminal ganglion after inferior alveolar nerve injury.. Journal of biological regulators and homeostatic agents, 31(1), 147-152.