Photobiomodulation (PBM) encompasses various non-invasive therapies involving biological tissue irradiation with light at specific wavelengths. This technique employs light sources, such as lasers and light-emitting diodes (LEDs), primarily within the visible and infrared spectrum. PBM therapy has been widely tested for its potential to modulate cellular processes, promote tissue repair, reduce inflammation, and alleviate pain [1].

In human medicine, it has been employed in the treatment of a wide range of conditions, such as chronic pain, wound healing, and musculoskeletal disorders [2]. In veterinary medicine, PBM has been predominantly used in both small and large animals to treat musculoskeletal injuries and neurological disorders, and in wound management [3].

PBM exerts its biological effects by stimulating chromophores within cells, particularly in the mitochondria.

By utilizing specific wavelengths of light to target tissues, PBM can stimulate biological processes reducing inflammation, alleviating pain, and enhancing cellular metabolism. While early interpretations suggested wavelength-specific effects, current understanding acknowledges that a variety of wavelengths may produce similar outcomes, provided that dosimetry is appropriately adjusted to account for the energy profile and optical behavior of each wavelength [4]– [5]. These outcomes are also influenced by wavelength-dependent tissue interactions, including attenuation, scattering, and absorption phenomena.

It has been suggested that PBM activates cellular signaling pathways and promotes the production of key molecules that support healing and tissue regeneration [6].

Despite these insights, the exact mechanism underlying light therapy remains poorly understood.

One theory proposes that photons interact with mitochondrial chromophores, especially cytochrome c oxidase (CCO), leading to the photodissociation of nitric oxide (NO). This process enhances electron transport, enzyme activity, and ATP production, which contribute to cellular repair and regeneration [1].

Recent evidence highlights additional photoreceptors involved in PBM, such as opsins and transient receptor potential (TRP) ion channels, which are sensitive to light or heat and may influence cell depolarization and signaling [7]– [8].

Chromophores like flavins, flavoproteins, and interstitial water may also play roles in PBM responses [9]. Redox reactions triggered by light exposure affect the cellular redox balance and influence gene expression and the synthesis of nucleic acids [10]. The release of NO from CCO enhances mitochondrial function and ATP production [11]. Reactive oxygen species (ROS), generated at low levels, act as secondary messengers in signaling cascades, rather than as cytotoxic agents. These molecular events lead to physiological outcomes such as improved wound healing, pain reduction, modulation of inflammation, enhanced muscle recovery, and neuroprotection following traumatic injury or stroke [12].

A wide variety of light-emitting sources are routinely utilized in clinical settings that comprehend the use of PBM. Red and near-infrared (NIR) are wavelengths most commonly used, although blue has been reconnoitered more recently for the treatment of superficial tissues. NIR is generally preferred for deeper tissue treatments due to its relatively lower absorption of the main absorbing molecules and less scattering compared to shorter wavelengths.

Nonetheless, recent studies indicate that over 90% of NIR energy is absorbed within the first 10 mm of biological tissue [13,14,15]. This presents a challenge for treating targets located beyond this depth. While it has been hypothesized that short pulses with high peak power could facilitate deeper photon delivery, it has been demonstrated that peak power alone is not a reliable determinant of effective energy deposition at depth, as differences in irradiance between low- and high-peak power systems tend to diminish due to scattering and absorption [13,14,15].

However, under specific conditions—such as those involving extremely short pulse durations, low duty cycles, and sufficient peak power, as demonstrated in the EMS 905 nm system studied by Kaub [13]– [14] —residual optical energy has been detected at depths up to 20 mm, at levels potentially relevant for biological activation. Although clinical implications remain to be established, this suggests that certain delivery strategies may help overcome some of the inherent optical limitations [13,14,15].

Based on the power of the emitted light lasers used in PBM treatment are classified into low-level laser therapy (LLLT) and high-power laser therapy (HPLT). LLLT refers to the use of lasers with an average beam power of less than 500 mW, used primarily for superficial tissues, and it is used to treat inflammatory processes and alleviate pain, while, HPLT, due to beam power greater than 500 mW, penetrates deeper tissues and is utilized for more significant therapeutic interventions, such as managing chronic pain and extensive musculoskeletal damage [12].

In recent years, the use of class IV high-power laser therapy (HPLT) devices has become increasingly common in both human and veterinary medicine. These systems can deliver high output powers, often in the range of 10–30 W or more; however, energy is typically applied over large areas using broad optical spot sizes and scanning techniques to maintain average irradiance within safe and biologically tolerable limits. Continuous lasers may deliver average irradiances of 30–100 mW/cm², while pulsed lasers can reach very high peak powers—up to 270 W/cm² or more—without exceeding thermal thresholds, due to the use of short duty cycles or gated emission modes. Some high-intensity systems, such as the Hiro® by ASA Laser and the Fotona Litewalker (Nd: YAG free-running pulsed system), can theoretically exceed 10,000 W/cm² in peak irradiance; however, the effective dose reaching the tissue remains controlled to avoid surface overheating, ensuring that tissue temperatures remain below 45 °C. For example, in the study by Looney et al. (2018), although a laser with a peak output capacity of 12 W was used, the energy was delivered over large areas (125–350 cm²) using a scanning technique, resulting in an estimated average irradiance of approximately 28–40 mW/cm². This highlights that peak output power alone is not indicative of the true irradiance delivered to the tissue, which depends on several factors including spot size, scanning speed, and emission mode.

In veterinary medicine, despite their frequent use, a lack of consensus on the most effective treatment protocols and therapeutic efficacy remains [12].

Several key parameters influence the clinical outcomes of Photobiomodulation Therapy (PBMT). One of the primary factors is the wavelength of the light, which affects tissue penetration and the biological response, followed by the beam coherence. While laser light is coherent (with waves in phase), LED light is typically non-coherent; however, both types are used in the treatment with PBMT [16].

Also, the therapy’s effectiveness is determined by the energy of the light beam and the power. The dose of light and the irradiance or power density, influence significantly tissue response to treatment. Additionally, the emission modality of the light source (continuous, frequency-based, or pulsed) may modulate the biological effects of PBM [17].

The overall success of PBMT is also affected by the total number of treatment sessions and the intervals between them, which determine the cumulative therapeutic impact on the tissue [12, 18]. Proper adjustment and combination of these parameters are essential for achieving the desired clinical outcomes.

PBMT typically follows a biphasic dose-response pattern; for certain purposes lower doses may be more effective than higher doses, indicating the need for an optimal dose tailored to each clinical scenario. Research regarding PBMT of chronic musculoskeletal pain in humans has shown improved outcomes with treatments employing higher power densities and consistent scheduled treatment.

Effective wavelengths for PBMT generally fall within the “optical window” range of 600 to 1070 nm. Lower wavelengths (600 to 700 nm) are typically used for targeting superficial tissues, while higher wavelengths (780 to 950 nm) are more suited for deeper tissue penetration [12, 18].

As highlighted by Zein et al. (2018) [19], for near-infrared PBM therapies, peak irradiance should generally remain below 750 mW/cm² to prevent undesired photothermal effects. Nevertheless, devices employing pulsed or gated emissions can achieve high peak powers while maintaining a low average irradiance, especially when combined with large spot sizes and continuous motion scanning. These delivery strategies are designed to keep tissue temperatures below 45 °C, minimizing the risk of heat-induced cellular damage.

Cronshaw et al. (2023) [20] further analyzed the photothermal behavior of high-intensity PBM systems, emphasizing that thermal safety is influenced not only by output power but also by beam geometry, spot profile (Gaussian vs. flat-top), and exposure time per unit area.

Among the various types of lasers, Multiwave Locked System (MLS®) represents a family of high-power, non-invasive, class IV therapeutic lasers. MLS® laser therapy has been reported to provide therapeutic benefits in clinical settings, particularly in pain relief and inflammation control, though further independent studies are warranted to fully establish its comparative effectiveness [21].

MLS® devices emit two different wavelengths within the NIR spectrum: 808 nm in continuous or frequency-modulated mode, and 905 nm in pulsed mode. The device configuration, protected by a technical patent from ASA srl, enables spatial and temporal synchronization of these two emissions. Although other manufacturers also employ dual-wavelength or coaxial emission systems, MLS® has been investigated in both clinical and preclinical settings. For example, Corti et al. [22] demonstrated improved clinical outcomes in patients with cervical pain using synchronized dual-wavelength therapy, while Gigo-Benato et al. [23] reported enhanced nerve regeneration in vivo compared to either wavelength alone. While these results are promising, further independent validation is needed to determine whether synchronization confers unique therapeutic advantages compared to other PBM configurations.

Mechanistically, the 808 nm wavelength has been shown to increase mitochondrial respiratory chain activity by targeting a secondary absorption peak of cytochrome c oxidase, while the 905 nm wavelength affects complexes I–IV and succinate dehydrogenase [24].

It has been hypothesized that combining these wavelengths may offer broader or synergistic biological effects compared to single-wavelength LLLT [25].

MLS® therapy has also been associated with the stimulation of angiogenesis, enhancement of cellular energy production, regulation of inflammatory processes, and modulation of fibroblast activity. Additionally, some reports note reduced treatment times with MLS® systems, which may facilitate integration into clinical practice, though these findings require further investigation [25].

This study conducts a systematic review of research on PBMT, with a particular focus on PBMT utilizing MLS® lasers, by employing text mining (TM) and topic analysis (TA) approaches to store and process data in digital formats. The primary rationale for using data mining techniques is their ability to efficiently store and process large datasets in digital formats. TM provides a method for exploring unstructured data, reducing errors and time expenditure while yielding more accurate insights [26].

The primary aim of this study is to identify prevailing research topics related to the use of PBMT in both human and veterinary medicine, with particular emphasis on MLS® lasers. Additionally, the secondary objectives are to provide an overview of the temporal trend of these topics, interpret their evolution over the past century, and identify potential research gaps.