PHOTOBIOMODULATION EFFICACY THROUGH IMPLANTED PHOTOTHERAPORTS AT PERIPHERAL AND SPINAL CORD LEVEL IN INFLAMMATORY PAIN

Light-based therapies are emerging due to their minimally invasive nature and ability to target specific body regions. Photobiomodulation (PBM) represents a promising, yet under-optimized, strategy for pain relief offering improved tolerance and fewer side effects compared to pharmacological treatments. However, a major limitation of PBM is the attenuation of light penetration by soft tissue and bones. Consequently, PhotoTheraPorts were developed as an innovative light delivery method based on biocompatible, long-lasting, and minimally invasive biophotonic implants with upconverting nanoparticles that emit customized light when excited by tissue-penetrating infrared light. This study evaluated the analgesic effect of upconverted PBM through implanted PhotoTheraPorts (red emission) at peripheral and spinal cord levels in formalin-and Complete Freund’s Adjuvant (CFA)-induced models of inflammatory pain. Peripheral PBM, delivered via PhotoTheraPort implanted in the hind paw, resulted in an analgesic action in males, acutely reducing the nocifensive response in the formalin model (phases I/II) and chronically increasing the mechanical paw threshold in the CFA-induced pain model. Spinal PBM, applied chronically via PhotoTheraPort implanted over the lumbar spinal cord, robustly increased mechanical and thermal nociceptive thresholds in both males and females. This analgesic effect was accompanied by reduced pCREB immunoreactivity in the dorsal horn of the spinal cord. No significant effects of PBM on paw edema or an IR light effect were found. These results demonstrate the efficacy of this innovative PBM therapy through implanted PhotoTheraPorts in treating inflammatory pain. This approach allows for specifically targeted light delivery with higher precision opening new avenues for light-based analgesia.