Transcranial Photobiomodulation Attenuates Neurogenic Inflammation and Sensory Hypersensitivity in a Nitroglycerin-Induced Migraine Model: Toward a Nonpharmacological Therapy.

BACKGROUND

Migraine is a debilitating neurological condition, characterized by headache, photophobia, and heightened mechanical/thermal sensitivity. Current pharmacological therapies often lead to incomplete relief and adverse effects, necessitating the use of noninvasive alternatives. This study evaluated transcranial photobiomodulation (PBM) in a nitroglycerin (NTG)-induced migraine model in male mice.

METHODS

Mice were assigned to Sham, NTG, NTG + Sumatriptan (SUMA; 600 µg/kg, s.c.), NTG + PBM, and NTG + PBM + SUMA groups. Over 9 days, NTG (5 mg/kg) was injected intraperitoneally every other day to develop an animal model of chronic migraine. The PBM protocol involved daily irradiation (810 nm) on the occipital bone of the head for 5 s over 9 days. The animals underwent behavioral testing for photophobia, mechanical allodynia, and thermal sensitivity. The trigeminal nucleus caudalis (TNC) was assessed for miR-155 expression by real-time PCR and protein expression of phospho-NF-κB, IL-1β, transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), calcitonin gene-related peptide (CGRP), c-Fos, and pituitary adenylate cyclase-activating polypeptide (PACAP) using immunoblotting.

RESULTS

Behavioral assessment revealed that PBM significantly reduced head scratching and improved exploratory activity, decreased light aversion, reversed periorbital/hindpaw mechanical allodynia, and prolonged thermal withdrawal latency compared to the NTG group. Moreover, PBM downregulated miR-155 expression and decreased levels of inflammatory mediators and migraine-associated neuropeptides in the TNC. Notably, combined PBM and SUMA treatment resulted in improvements in behavioral and molecular outcomes compared to either treatment alone.

CONCLUSION

These results indicate that PBM inhibited migraine-like behaviors and decreased the expression of numerous molecular markers that are linked to neuroinflammation and trigeminal activation in the TNC. These findings establish a foundation for additional research on transcranial PBM as a noninvasive method for modulating migraine-related behavioral responses.