Green Light Therapy and Brain Mechanisms of Pain and Anxiety

University Of Maryland Baltimore, Baltimore MD

Investigators

Abstract

ABSTRACT AND PROJECT SUMMARY In the USA, more than 50 million adults suffer from chronic pain, with women disproportionately affected. As many as 60% of chronic pain patients also suffer from mood disorders, with women being twice as likely to be affected by anxiety disorder. Effective treatment for chronic pain and comorbid anxiety, especially when considering sex-dependent factors, is still inadequate. An increasing number of studies provide strong evidence that green light therapy reduces hypersensitivity in neuropathic, inflammatory, and post-surgical pain models. Clinical studies on migraine, fibromyalgia, and pain during dental procedures also support these findings, showing that green light-emitting diodes (GLED) exposure alleviates pain and anxiety without adverse side effects. While the neurobiological mechanisms of GLED analgesia have been proposed, it remains unclear how GLED exposure influences global brain networks related to pain and anxiety, and whether its effects differ by sex. Our prior work has shown that in a chronic osteoarthritis (OA) model in rats, GLED exposure effectively reduces hypersensitivity in both sexes, but with more pronounced effects in males. Functional MRI (fMRI) has revealed enhanced connectivity between the rostral anterior cingulate cortex and the periaqueductal gray in GLED-exposed males, which is associated with stronger pain inhibitory responses. In contrast, only females exhibit increased anxiety-like behaviors associated with enhanced connectivity between the amygdala and hippocampus, which GLED exposure reverses. These findings suggest that GLED modulates pain and anxiety circuits, highlighting the need for further research on sex-dependent effects and whole-brain networks. In this project, we will test the hypothesis that GLED exposure reduces pain-like behaviors by enhancing descending pain inhibitory circuits and alleviates anxiety-like behaviors by acting through emotion circuits, both of which are modulated by sex in chronic pain. In specific aim (SA) 1, we will use a comprehensive set of behavioral assays to determine the effects of GLED exposure on pain- and anxiety-like behaviors and descending pain modulation, and their relationship with sex in a rat model of chronic OA pain. In SA2, we will conduct an fMRI study using network and mediation analyses to assess the effects of GLED exposure on the longitudinal changes in whole- brain connectivity associated with pain and anxiety. In SA3, we will determine how specific brain circuits may mediate GLED-induced analgesia and reduction in anxiety-like behaviors using simultaneous chemogenetics- fMRI. This project will significantly improve our knowledge of the central mechanisms underlying GLED effects on pain and anxiety in males and females, providing a strong basis for advancing GLED therapy as an evidence- based treatment strategy for chronic pain and comorbid anxiety, potentially tailored by sex.