People with MS (pwMS) often experience self-reported symptomatic fatigue (Kos et al., 2008). Muscle fatigue, or fatigability, defined as a decrease in maximal force generating capacity of a muscle after a fatiguing task (Bigland-Ritchie and Woods, 1984; Enoka and Duchateau, 2016), has also been widely reported in pwMS (Sheean et al., 1997; Zijdewind et al., 2016); the contribution of muscle fatigue to symptomatic fatigue remains unclear (Zijdewind et al., 2016). Muscle fatigue in MS may originate from central mechanisms as a consequence of MS or peripheral mechanisms possibly secondary to deconditioning or disuse, such as impaired mitochondrial function (Sheean et al., 1997; Kent-Braun et al., 1994; DePauw et al., 2021). Despite the presence of various medical and rehabilitative interventions, including exercise (Kalb et al., 2020), to alleviate MS symptoms, there is currently no effective treatment targeting muscle fatigue.

Photobiomodulation Therapy (PBMT) uses low-level laser light-emitting diodes (LED) to deliver red/near-infrared light (R/NIR, 600–1100 nm) to treat soft tissue injury (Posten et al., 2005), chronic inflammation (Christie et al., 2007), and pain (Chow and Armati, 2016). PBMT's proposed mechanism involves the absorption of R/NIR light by mitochondrial cytochrome c oxidase, leading to enhanced mitochondrial function, including increased oxidative phosphorylation and nitric oxide (NO) production, to increased intracellular Ca2+, improved cell function, and reduced apoptosis (Chung et al., 2012; Eells et al., 2004; de Freitas and Hamblin, 2016). The efficacy of PBMT follows a biphasic dose-response curve (Huang et al., 2009), indicating an optimal dose for maximum therapeutic outcomes. Previous studies in healthy individuals demonstrated the effectiveness of PBMT on muscle force recovery and fatigue after exercise (Larkin-Kaiser et al., 2015; Larkin-Kaiser et al., 2016). Given the evidence supporting the benefits of PBMT on muscle in healthy individuals, it can be hypothesized that PBMT might benefit muscle function in pwMS by improving muscle mitochondrial function. Although there is evidence on the immune-modulating effects of PBMT in pwMS (Tolentino et al., 2019; Tolentino et al., 2022) it is unknown if muscle function can be enhanced by PBMT in pwMS.

We conducted a two-part pilot study to investigate the effects of PBMT on muscle function in pwMS. In study I, we examined the short-term effects of PBMT on muscle force recovery and fatigue in pwMS, while also determining the optimal PBMT dose. We hypothesized that PBMT would improve muscle function in pwMS, in a dose dependent manner. In study II, we evaluated the impact of extended PBMT on muscle strength, endurance, and fatigue in pwMS. We hypothesized that prolonged PBMT would improve muscle function in pwMS.