Wavelength dependent effects of red and infrared photobiomodulation on neuropathic pain, skeletal muscle integrity, and mitochondrial respiration

Neuropathic pain is a chronic and difficult to treat condition affecting up to 10% of the population, significantly impairing quality of life and representing a public health concern. Photobiomodulation (PBMT) has emerged as a promising therapeutic approach, as photons can reach mitochondria and promote beneficial effects, including increased ATP production, reduced oxidative stress and inflammation, and improved mitochondrial metabolism and regeneration. However, gaps remain regarding its effects on mitochondrial dynamics in neuropathic pain. This study investigated the impact of PBMT at two wavelengths (660 nm, red and 904 nm, infrared) on nociceptive behavior (tactile allodynia, mechanical and thermal hyperalgesia), histological alterations, mitochondrial respiration, and protein expression by Western blotting in an experimental neuropathic pain model in male Wistar rats. PBMT reduced mechanical hyperalgesia and tactile allodynia, decreased inflammatory features, and promoted hyporadiance detected by infrared thermography. Chronic constriction of the sciatic nerve significantly reduced mitochondrial respiration in the gastrocnemius muscle. Although PBMT did not restore mitochondrial respiratory capacity, it induced relevant molecular alterations in mitochondrial proteins. Specifically, PBMT increased the expression of OPA1, a key regulator of mitochondrial dynamics, and modulated components of the electron transport chain and ATP synthase in a wavelength-dependent manner. Overall, PBMT modulated nociception and promoted mitochondrial molecular adaptations. These findings suggest that PBMT-induced analgesia may involve mechanisms independent of skeletal muscle mitochondrial bioenergetic restoration. Distinct wavelength-dependent responses further contribute to therapeutic parameter optimization and support future translational and clinical research. Clinical trial number: not applicable.