Near-infrared photobiomodulation can alleviate chemotherapy-induced peripheral neuropathy-associated sensory abnormalities

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious side effect of paclitaxel-based chemotherapy, with limited therapeutic options that often prove ineffective. Photobiomodulation (PBM), a non-invasive therapeutic approach utilizing near-infrared light, has shown promise in fostering nerve regeneration and modulating inflammatory responses. This study aimed to assess both the therapeutic efficacy and the underlying molecular mechanisms of PBM in a preclinical model of CIPN.

Methods: The effects of 808 nm near-infrared PBM were evaluated in both in vivo and in vitro CIPN models. A murine CIPN model was developed and subjected to three weeks of continuous PBM treatment. Behavioral assessments, intraepidermal nerve fiber (IENF) density analysis, and mitochondrial ultrastructural evaluations were performed in the in vivo experiments. For in vitro investigations, N2a neuroblastoma cells and normal human astrocytes (NHA) were exposed to albumin-bound paclitaxel (nab-paclitaxel), with or without PBM therapy. Cellular assays were conducted to evaluate cell viability, inflammatory cytokine secretion, oxidative stress levels, mitochondrial functionality, and Apoptosis.

Results: PBM significantly ameliorated mechanical and cold hypersensitivity in CIPN mice, restored IENF density, preserved mitochondrial ultrastructure, and reduced oxidative tissue damage. In addition, PBM enhanced neuronal cell proliferation, reduces the expression of pro-inflammatory cytokines, attenuated oxidative stress, stabilized mitochondrial membrane potential, increased ATP production, and inhibited paclitaxel-induced Apoptosis through regulation of the mitochondrial pathway.

Conclusions: Near-infrared PBM effectively mitigates CIPN by promoting neural repair, suppressing neuroinflammation and oxidative stress, and preserving mitochondrial function. These findings highlight PBM as a potential non-pharmacological therapeutic option for CIPN management and suggest that further clinical investigations are warranted.

Albumin-bound paclitaxel; Chemotherapy-induced peripheral neuropathy; Mitochondrial dysfunction; Oxidative stress; Photobiomodulation.