Photobiomodulation on NMES-Induced Muscle Fatigue and Damage: A Pilot Study

EFEITOS DA FOTOBIOMODULAÇÃO E DOS SÍTIOS DE ESTIMULAÇÃO SOBRE A FADIGA E DANO MUSCULAR INDUZIDOS POR ESTIMULAÇÃO ELÉTRICA NEUROMUSCULAR EM INDIVÍDUOS SAUDÁVEIS

Neuromuscular electrical stimulation (NMES) is an effective tool for muscle strengthening and rehabilitation, but its clinical application is often limited by rapid neuromuscular fatigue, muscle discomfort, and potential muscle damage. Photobiomodulation therapy (PBMT) using low-level lasers or LEDs has been proposed as an ergogenic and protective modality capable of attenuating exercise-induced muscle fatigue and damage. However, evidence regarding the acute preventive effects of PBMT on NMES-induced fatigue and muscle damage in humans remains limited and conflicting.

The purpose of this randomized, sham-controlled, crossover pilot trial was to evaluate the acute effects of PBMT applied prior to an NMES-induced fatigue protocol on knee extensor neuromuscular fatigability, muscle damage, discomfort, and functional performance in healthy young individuals. Healthy participants had both lower limbs randomized to receive either active PBMT (810 nm, 240 J total per limb across 8 points) or sham PBMT 5 minutes prior to an NMES fatigue protocol (20 minutes of evoked isometric contractions at 20% of maximal voluntary contraction). Primary and secondary outcomes-including maximal voluntary isometric contraction (MVIC) torque, supramaximal twitch torque, muscle damage via ultrasound echointensity (rectus femoris and vastus lateralis), pain pressure thresholds (algometry), visual analog scale (VAS) for discomfort, and functional tests (Single Hop Test and stair ascent/descent)-were assessed at baseline, immediately post-fatigue, and at 24, 48, and 72 hours post-intervention.

BACKGROUND & RATIONALE:

Neuromuscular electrical stimulation (NMES) is widely employed in physical rehabilitation to counteract muscle atrophy, restore muscle strength, and enhance functional recovery across clinical and sports populations. However, NMES-induced muscle contractions recruit motor units in a non-selective, spatially fixed, and temporally synchronized pattern, leading to premature muscle fatigue, discomfort, and structural muscle damage. Photobiomodulation therapy (PBMT) using low-level laser therapy (LLLT) has been shown to improve mitochondrial ATP synthesis, reduce oxidative stress, and accelerate neuromuscular recovery. This pilot trial was designed to investigate whether pre-exercise PBMT attenuates NMES-induced fatigue, mitigates muscle damage, reduces discomfort, and preserves functional performance in healthy individuals.

STUDY DESIGN & RANDOMIZATION:

This study was a randomized, sham-controlled, single-blind, crossover pilot clinical trial conducted at the Neuromuscular Plasticity Laboratory (LAPEX / ESEFID - UFRGS). Both the dominant and non-dominant lower limbs of healthy participants were evaluated across a 9-day experimental protocol:

• Day 1: Familiarization with isokinetic dynamometry, NMES, ultrasound imaging, and functional performance tests.
• Days 2 to 5 (First Limb): Baseline assessments, application of the randomized intervention (Active PBMT or Sham PBMT) followed by the NMES fatigue protocol on Day 2, with follow-up evaluations immediately post-fatigue, and at 24 hours (Day 3), 48 hours (Day 4), and 72 hours (Day 5).
• 7-Day Washout Period.
• Days 6 to 9 (Contralateral Limb): Identical experimental sequence applied to the contralateral limb receiving the alternate intervention condition.

INTERVENTIONS:

1. Active PBMT: Applied 5 minutes before the fatigue protocol using a multi-diode cluster probe (Thor Photomedicine Ltd., UK) containing five GaAlAs laser diodes (wavelength: 810 nm; output power: 200 mW per diode; continuous wave mode). Irradiation was performed in stationary direct skin contact at a 90° angle across 8 anatomical sites on the quadriceps femoris (3 sites on rectus femoris, 3 on vastus lateralis, and 2 on vastus medialis). Each point was irradiated for 30 seconds at 30 J/point (6 J/diode), delivering a cumulative energy dose of 240 J per limb. Both participants and operators wore wavelength-specific protective goggles, and participants wore acoustic headphones to maintain blinding against auditory device cues.
2. Sham PBMT: Identical probe placement, treatment duration, and acoustic masking applied without active laser light emission (device turned off).

NMES FATIGUE PROTOCOL:

Evoked isometric fatigue was induced on a Biodex System 3 Pro isokinetic dynamometer with the knee fixed at 90° flexion. Electrical stimulation was delivered via a custom multifunctional stimulator using rectangular biphasic symmetrical pulses (pulse duration: 1 ms; frequency: 100 Hz; ON:OFF cycle of 5 s:10 s with 1 s linear ramps) for 20 minutes (60 analyzed evoked contractions). Current intensity was individually adjusted to evoke an initial isometric torque equivalent to 20% of baseline Maximal Voluntary Isometric Contraction (MVIC).

OUTCOME ASSESSMENTS & TIME POINTS:

All outcomes were evaluated at Baseline, Immediately Post-Fatigue, and at 24h, 48h, and 72h post-protocol:

1. Neuromuscular Fatigability: Knee extensor MVIC torque (Biodex dynamometer), supramaximal evoked twitch torque (1 Hz single pulse), evoked neuromuscular efficiency (torque/current ratio), total mechanical work (torque-time integral), and fatigue index (% work decline).
2. Muscle Damage: Quantitative transverse ultrasound echointensity (grayscale histogram analysis using ImageJ) of the rectus femoris (at 40%, 50%, and 60% of the femur length) and vastus lateralis (at 50% femur length).
3. Discomfort & Pain Sensitivity: Visual Analog Scale (VAS, 0-10 cm) for sitting discomfort and during a stair ascent/descent test, alongside pain pressure threshold (PPT) measured via digital pressure algometry over the rectus femoris, vastus lateralis, and vastus medialis.
4. Functional Performance: Single Hop Test (SHT, normalized to limb length) and stair ascent/descent timed test.

Inclusion Criteria:

• Healthy male and female adults aged between 18 and 40 years.
• Engaging in regular physical activity (minimum of twice a week).
• No history of hospitalization for COVID-19 in the past 12 months.
• Demonstrated ability to tolerate neuromuscular electrical stimulation (NMES).
• Capable of fully understanding and complying with the experimental protocol and procedures.

Exclusion Criteria:

• Presence of any sensory impairments or neurological alterations.
• Ingestion of caffeine, coffee, energy drinks, or other stimulants in the 12 hours preceding the testing sessions.
• Body Mass Index (BMI) greater than 30 kg/m².
• Any medical contraindication to performing maximal physical exertion or presenting an abnormal cardiovascular/blood pressure response after maximal effort.