Effectiveness of Photobiomodulation Therapy in the Management of Fibromyalgia Syndrome: A Systematic Review

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This study supports the use of photobiomodulation therapy as an adjunctive treatment for Fibromyalgia syndrome, promoting its integration into multidisciplinary pain management. PBMT exerts therapeutic effects by modulating oxidative stress, enhancing mitochondrial function, and regulating nociceptive pathways, contributing to pain relief, better sleep, and improved function. Standardized protocols and high-quality trials are needed to facilitate its clinical implementation.

Abstract

Fibromyalgia syndrome is a chronic pain condition involving altered nociceptive processing, which requires multidisciplinary management. Photobiomodulation therapy (PBMT) has recently emerged as a promising non-pharmacological approach, but its clinical effectiveness and optimal application methods remain unclear. This systematic review evaluated the efficacy of PBMT in managing Fibromyalgia symptoms, including pain, physical function, sleep quality, and overall well-being, while comparing localized and whole-body delivery. A systematic review was conducted in accordance with the PRISMA guidelines and previously registered on PROSPERO (CRD42024626368). Literature searches were performed across MEDLINE ((PubMed)), PEDro, SPORTDiscus, Scopus, Elsevier (ScienceDirect), and Web of Science (WOS), identifying 17 eligible studies (n = 857 participants). PBMT was applied via low-level laser, infrared, or LED-based devices, delivered either locally or to the whole body. The methodological quality of the studies was assessed using the PEDro scale, and the risk of bias was evaluated using the RoB 2.0 tool. PBMT showed significant clinical benefits, including reduced pain intensity, improved physical function, decreased fatigue, and enhanced quality of life. Whole-body PBMT showed greater and more sustained effects than localized applications, likely due to its systemic modulation of nociceptive pathways and autonomic regulation. Improvements were also observed in terms of psychological well-being, sleep quality, and reduced kinesiophobia. In conclusion, PBMT appears to be an effective therapeutic option for Fibromyalgia syndrome, with whole-body applications offering superior benefits. However, the variability in treatment parameters and study methodologies underscores the need for standardized protocols and high-quality clinical trials to support its integration into multidisciplinary pain management strategies.

1. Introduction

Fibromyalgia is a chronic musculoskeletal pain syndrome characterized by central sensitization, a process through which the central nervous system becomes hyperreactive and amplifies nociceptive signals, leading to widespread pain and heightened pain perception [1,2]. Beyond persistent pain, Fibromyalgia syndrome manifests as a complex, multifaceted condition involving fatigue [3,4], morning stiffness [5], sleep disturbances [6], and cognitive impairments, such difficulties in regard to concentration and memory deficits [7].

Although it predominantly affects women aged 20–50 years [8], it is also observed in men [9], adolescents [10], and older adults [11]. The etiology of Fibromyalgia is multifactorial, encompassing genetic predisposition [12], chronic stress [13], mood disorders [14], and associations with rheumatic diseases (e.g., rheumatoid arthritis [15], lupus [16]) and infectious agents (e.g., Epstein-Barr virus [17]). Globally, Fibromyalgia affects approximately 2.1% of the population, with a slightly higher prevalence in Europe (2.31%) and Spain (2.4%) [18,19]. The syndrome significantly diminishes the patient’s quality of life (QoL), affecting physical, emotional, and social domains, while also imposing a substantial socioeconomic burden, due to increased healthcare usage and work absenteeism [20,21].

The standard approach to Fibromyalgia management is multidisciplinary, integrating pharmacological treatments, including analgesics, antidepressants, and anticonvulsants, with structured physical exercise, cognitive-behavioral therapy, and patient education [22,23,24]. While these interventions can alleviate symptoms and enhance daily functioning, their efficacy varies among individuals, and adherence to treatment regimens is often limited. Additionally, the strong placebo effect observed in regard to Fibromyalgia therapies underscores the need for novel, evidence-based interventions that offer reliable symptom relief.

Photobiomodulation therapy (PBMT) has recently emerged as a promising complementary treatment for Fibromyalgia and other chronic pain conditions [25,26]. This non-invasive technique uses low-level lasers or light-emitting diodes (LEDs) to deliver light within specific wavelengths, typically within the red to near-infrared range (600–1100 nm), to target tissues. These wavelengths are selected based on their proven ability to penetrate tissue effectively and interact with mitochondrial chromophores, particularly cytochrome c oxidase (CCO), thereby modulating cellular processes that may reduce pain and inflammation, while promoting tissue repair [27]. Mechanistically, PBMT has been shown to enhance mitochondrial ATP production, reduce oxidative stress, and modulate gene expression related to pain signaling pathways, contributing to its potential therapeutic effects [28].

Preliminary findings suggest that PBMT may alleviate Fibromyalgia-related symptoms, such as chronic pain, fatigue, and psychological disturbances, including kinesiophobia and reduced self-efficacy. However, given the complex and multifactorial nature of fibromyalgia, characterized by heterogeneous symptom profiles and diverse pathophysiological mechanisms, the current evidence supporting PBMT remains inconclusive and poorly understood. This complexity contributes to the wide variability in PBMT protocols, with no clear consensus regarding optimal wavelengths, session durations, treatment frequencies, or long-term safety [29,30]. In this context, a systematic review is warranted to critically appraise and synthesize the available evidence, identify methodological gaps, and evaluate the consistency and quality of outcomes reported across studies. Such a review is essential to guide future research, inform clinical practice, and assess the potential for developing standardized, evidence-based treatment protocols.

Therefore, the aim of this systematic review is to evaluate the effectiveness of PBMT as a complementary therapy for Fibromyalgia syndrome, with a particular focus on outcomes related to pain reduction, functional improvements, and enhancement of the quality of life (QoL) of patients. Additionally, this study seeks to explore potential moderating factors that may influence treatment outcomes and to provide evidence-based recommendations to optimize the clinical application of PBMT in this patient population.

2. Materials and Methods

2.1. Data Source and Search Strategy

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [31]. The protocol for this systematic review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO CRD42024626368). A comprehensive literature search was performed from 11 December 2024 to 4 February 2025, to identify all available studies on the effectiveness of PBMT in patients with Fibromyalgia for managing pain, sleep disturbances, functionality, and QoL. The databases consulted included MEDLINE (PubMed)), PEDro Database, SPORTDiscus, Scopus, Elsevier (ScienceDirect), and Web of Science (WOS).

In MEDLINE, the following search equation was used: “Photobiomodulation therapy” [Mesh] OR “Green light-based analgesia” [Mesh] OR “Morning light treatment” [Mesh] OR “Fibromyalgia” [Mesh] OR “Fatigue Syndrome, Chronic” [Mesh] OR “Musculoskeletal Pain” [Mesh] OR “Chronic Pain” [Mesh] OR “Placebo Effect” [Mesh] OR “Low frequency laser therapy” [tiab] OR “LEDs light therapy” [tiab] OR “Sleeping disorders” [tiab] OR “Functionality” [tiab] OR “Quality of life” [tiab] OR “Placebo treatments” [tiab] OR “Biopsychosocial factors” [tiab]. Equivalent search strategies were applied for PEDro, SPORTDiscus, Scopus, Elsevier (ScienceDirect), and Web of Science (WOS). The search was independently conducted by two reviewers, while a blinded third reviewer evaluated all the retrieved articles, based on their titles and abstracts. The full-text articles were subsequently assessed to determine eligibility. In cases of disagreement, a fourth reviewer (S.E.M.P) acted as the final referee. The detailed search strategy is provided in Table S1: Search strategy.

2.2. Selection of Studies

The inclusion criteria for this systematic review were as follows: the studies had to be (1) randomized controlled trials, non-randomized clinical trials, or retrospective clinical studies; (2) a full text was available; (3) published in English, Spanish, or French; and (4) published since the inception of the databases. Eligible studies included participants (5) diagnosed with Fibromyalgia syndrome, who (6) underwent PBMT (e.g., Low-Level Laser Therapy, Light-Emitting Diode Therapy, Infrared Therapy, Helium-Neon Laser Therapy, Superluminous Diode Therapy, and Pulsed-Laser Therapy) as the main intervention. Additionally, studies were required to report (7) on the outcomes related to at least one primary variable: pain intensity, sleep disturbances, physical functionality, QoL.

Studies were excluded if they (1) were not based on eligible study designs (e.g., case series, case reports, editorials, letters to the editor, commentaries, systematic or narrative reviews), (2) lacked full-text availability, (3) were not published in English, Spanish, or French, (4) did not include patients diagnosed with Fibromyalgia syndrome, (5) did not use PBMT as the main intervention, or (6) did not report outcomes related to at least one of the aforementioned primary variables or secondary variables, such as the pain pressure threshold (PPT), morning stiffness, anxiety, or depression.

2.3. Data Extraction

Data extraction was independently conducted by three authors (R.C.L., J.R.N., and L.G.P.), who resolved discrepancies through discussion and consensus. A standardized table template based on the PICO framework was used to systematically collect and organize all the relevant information, including author details, year and country of publication, study design, objectives, main findings, and participant characteristics (such as disease profile, medical intervention, sample size, and gender distribution, etc.), intervention and control details, outcome measures, and conclusions. The Cochrane Handbook for Systematic Reviews of Interventions (v. 5.1.0) guided the development of these sections. The reliability of the extraction table was tested using a representative sample of the studies under review.

2.4. Methodological Quality Assessment: PEDro Scale

The PEDro scale was used to independently evaluate the methodological quality of the clinical trials included in this review, which was carried out by D.M.T. and A.L.M. [32]. The scale comprises 11 items, each worth one point, and assesses whether a randomized clinical trial has sufficient internal validity (criteria 2–9) and statistical information to ensure interpretability (criteria 10–11). Studies scoring between 9 and 10 were considered of excellent methodological quality, those scoring between 6 and 8 were of good methodological quality, and those scoring below 4 were categorized as of poor methodological quality.

2.5. Risk of Bias Assessment: ROB 2.0

The risk of bias for randomized clinical trials was independently assessed by D.M.T. and A.L.M., using the Cochrane Risk of Bias tool for randomized trials (RoB 2.0) [33]. This tool evaluates the methodological approach across five domains: (1) the randomization process, (2) deviations from the intended interventions, (3) missing outcome data, (4) outcome measurement, and (5) the selection of the reported results. The interpretation of the scores classified a low risk of bias as unlikely to alter the results significantly, while a high risk of bias reduced the confidence in the findings. Disagreements among authors were resolved through discussion and, in cases of contradictory ratings, the third reviewer (S.E.M.P.) made the final decision.

2.6. Quality of Evidence: GRADE

The certainty of the evidence was established using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework [34], which evaluates five domains: study design, imprecision, indirectness, inconsistency, and publication bias. Evidence was classified into four levels: high quality (all domains satisfied), moderate quality (one domain unsatisfied), low quality (two domains unsatisfied), and very low quality (three or more domains unsatisfied).

3. Results

3.1. Study Selection

A total of 559 studies were identified through searches in various databases, including MEDLINE (PubMed) (n = 112), PEDro (n = 24), SPORTDiscus (n = 15), Scopus (n = 265), Elsevier (ScienceDirect) (n = 132), and Web of Science (WOS) (n = 11). After removing 150 duplicate records, 409 studies remained for screening.

Subsequently, 186 studies were excluded based on title and abstract screening. The remaining 223 studies were retrieved for full-text review to assess their eligibility.

Of these, 206 studies were excluded for the following reasons: publication in languages other than English or Spanish (n = 25), lack of full-text availability (n = 50), non-comparable interventions (n = 13), different study populations (n = 20), study designs not aligned with the inclusion criteria (n = 80), and outcomes not relevant to the research question (n = 18). Ultimately, 17 studies met all inclusion criteria and were included in the qualitative synthesis. The study selection process is illustrated in Figure 1. Flow diagram of study selection (PRISMA 2020).

3.2. Characteristics of Included Studies

The 17 included studies represented a variety of clinical trial designs [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Among them, three were single-arm trials, including one feasibility trial with an embedded qualitative component [36] and two open-label longitudinal studies [46,47]. Six studies were randomized, triple-blinded, placebo-controlled trials [38,40,41,42,43,48], one of which was a multicenter study [40]. Two were randomized, double-blinded, controlled trials [35,49]; one was a randomized, crossover, double-blinded trial [45]; one was a randomized, single-blinded clinical trial [47]; and one was an observational retrospective study [44]. Several studies incorporated comparative interventions, including local anesthetic injections [47], functional exercise [48], and green light therapy [39,43].

All studies focused on Fibromyalgia and chronic pain syndromes, comprising a total of 857 patients (843 women, 98.4%; 14 men, 1.6%), aged 18–75 years. PBMT was the primary intervention across all the studies, with variations in wavelengths, dosage regimens, and application techniques. Several studies evaluated whole-body PBMT using NovoTHOR^® beds (THOR Photomedicine Ltd., Amersham, UK) [38,41,42], while others employed high-output laser systems, such as the FibroLux™ System (FibroLux GmbH, Hofheim, Germany) [40], the LCT-1000 Class IV laser (LiteCure^® LLC, Newark, DE, USA) [50], or Class IIIb lasers like Frank Line IR 30 (Fysiomed^®, Edegem, Belgium) [51]. Localized photobiomodulation targeting specific anatomical regions, such as tender points, muscles, or painful areas, was administered using devices like Antares^® (IBRAMED, Amparo, Brazil) [35], LasoRehab Advanced LS2200^® (Nu-Tek Health Inc., Hong Kong, China) [47], and Photon Laser III^® (DMC Equipamentos, São Carlos, Brazil) [48]. In addition, multimodal interventions were explored, such as the combination of photobiomodulation and therapeutic ultrasound using a patented prototype device (MMOptics BR102014007397-3 A2^®, São Carlos, Brazil) [46], or a super-pulsed laser combined with LEDs and magnetic fields, as in Pain Away/PainCure™ (Multi Radiance Medical^®, Solon, OH, USA) [49].

One study also tested a whole-body thermal therapy via water-filtered infrared A (wIRA-WBH), using IRATHERM1000^® (Von Ardenne Institut für Angewandte Medizinische Forschung GmbH, Dresden, Germany) [37]. For non-invasive visual interventions, green light-emitting diodes (GLEDs) were applied via ambient exposure (Led Supply^®, Randolph, VT, USA) [43], and green light-filtering eyeglasses were tested as a passive visual neuromodulation strategy, without the use of LEDs or lasers [39]. Three studies compared PBMT to placebo treatments [38,40,49], while others combined PBM with exercise therapy [35,40,48], therapeutic ultrasound [46], or alternative treatments like green light exposure [39,43].

The primary outcome variables assessed included QoL, pain intensity, functionality, and sleep disturbances [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Several secondary variables were also measured, such as the pressure pain threshold [38,42], morning stiffness [35,47], depression and anxiety [36,39,43], cognitive impairment [36,47], central sensitization [41,42], muscle spasms [47], and opioid medication reduction [39]. Study durations ranged from four weeks [38] to seven months [40], reflecting a broad range of treatment protocols.

The studies were conducted across multiple countries. Brazil accounted for five studies [35,40,45,46,49], followed by Spain with three [38,41,42], and the United States with three [36,43,50]. Two studies were performed in Turkey [47,51], while Germany [37], Italy [39], South Korea [44], and the United Kingdom [36] each contributed one study. Further details can be found in Table S2: Characteristics of the included studies.

3.3. Methodological Quality Assessment

The methodological quality of the 17 included studies was assessed using a standardized evaluation method, yielding an average score of 8.38 (SD = 0.62). All the studies were classified as having good-to-excellent methodological quality. Among them, six studies achieved the highest score of 9 [35,38,40,42,45,49], indicating robust methodological rigor, while the remaining studies received scores of 7 out of 10 [39] or 8 out of 10 [36,37,41,43,44,46,47,48,50], maintaining good quality standards.

All the studies specified the eligibility criteria and employed randomized allocation, except for three non-randomized or single-arm trials [36,46,50], which introduced potential systematic errors due to the absence of control groups and participant blinding issues. The blinding of therapists and investigators was conducted in a majority of the studies [35,37,38,39,40,41,42,44,48,49], reducing bias risks in regard to intervention delivery and outcome assessment. However, in some cases, either the therapists or participants were aware of the intervention received, potentially influencing subjective outcome measures.

Despite maintaining good quality, three studies employed retrospective or crossover designs [44,50,51], which, while offering valuable insights, may limit the generalizability of their findings. Furthermore, ongoing studies at the time of data extraction [40,42] may have influenced data completeness and the final statistical power. These findings emphasize the need for rigorous methodological approaches and further high-quality trials to confirm the effectiveness of the interventions evaluated. More details can be found in

Table 1. Methodological quality analysis (PEDro scale).

Author, Year	Score	Quality	1	2	3	4	5	6	7	8	9	10	11
Vassão et al. (2024) [35]	9	Excellent	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
Fitzmaurice et al. (2023) [36]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Langhorst et al. (2023) [37]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Navarro-Ledesma et al. (2023) [38]	9	Excellent	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes
Nelli et al. (2023) [39]	7	Good	Yes	Yes	Yes	Yes	No	No	Yes	Yes	No	Yes	Yes
Ribeiro et al. (2023) [40]	9	Excellent	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes
Navarro-Ledesma et al. (2022) [41]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Navarro-Ledesma et al. (2022b) [42]	9	Excellent	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes
Martin et al. (2021) [43]	8	Good	Yes	Yes	Yes	Yes	No	No	Yes	Yes	Yes	Yes	Yes
Choi et al. (2021) [44]	8	Good	Yes	Yes	No	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
dos Santos et al. (2020) [45]	9	Excellent	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
Junior et al. (2021) [46]	9	Excellent	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	Yes
Ates et al. (2019) [47]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Maciel et al. (2018) [48]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
da Silva et al. (2017) [49]	9	Excellent	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
Panton et al. (2013) [50]	8	Good	Yes	Yes	Yes	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Gür et al. (2002) [51]	7	Good	Yes	Yes	No	Yes	Yes	No	Yes	Yes	No	Yes	Yes

Methodological quality assessment of the included studies was conducted using the PEDro scale [32], which consists of 11 items: (1) eligibility criteria (not scored), (2) random allocation, (3) concealed allocation, (4) baseline comparability, (5) blinding of subjects, (6) blinding of therapists, (7) blinding of assessors, (8) adequate follow-up (>85%), (9) intention-to-treat analysis, (10) between group statistical comparisons, and (11) reporting of point estimates and variability. The total PEDro score ranges from 0 to 10 (excluding item 1), with higher scores indicating greater methodological quality.

: Methodological quality analysis (PEDro scale).

3.4. Risk of Bias Assessment

The risk of bias, assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool, varied across the included studies, ranging from low to serious [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. A low risk of bias was observed in regard to the randomization process and deviations from the intended interventions, with most studies maintaining methodological rigor [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Over 60% of the studies showed a low risk of bias in these domains, ensuring proper randomization and adherence to intervention protocols [35,36,38,40,42,43,44,45,46,48,49,50].

However, a moderate-to-serious risk of bias was noted in regard to missing outcome data and outcome measurement, raising concerns about incomplete datasets and assessment inconsistencies [35,37,39,41,43,44,47,49,51]. Notably, 35–40% of the studies displayed serious risk in these areas, which may affect the reliability of the reported results [35,37,39,41,43,44,47,49,51]. Selection of the reported results also showed a moderate-to-serious risk, suggesting selective reporting or inconsistent findings [35,36,37,39,40,42,45,47,50].

The randomization process was adequate in most studies, although two studies failed to ensure proper sequence concealment, increasing selection bias risk [46,50]. The blinding of outcome assessors was also incomplete in several studies, potentially influencing subjective assessments [36,46,47,49,51]. Overall, while many studies showed a low-to-moderate risk of bias, missing data and outcome measurement require careful interpretation [35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. Further details on the risk of bias assessment are available in Figure 2.

3.5. Grade of Recommendation

The GRADE evaluation of PBMT for Fibromyalgia suggests that there is moderate-to-high quality evidence supporting its efficacy in reducing pain, improving the patient’s QoL, and enhancing self-efficacy. Pain intensity was assessed in six studies (n = 250) [35,36,37,38,39,40], consistently demonstrating clinically significant reductions, with moderate certainty in terms of the evidence and a moderate recommendation in favor. QoL was evaluated in five studies (n = 210) [35,36,38,40,41], showing moderate-to-strong improvements in the patient’s daily activities and overall well-being, with a low risk of bias and a strong recommendation. Fatigue levels were analyzed in three studies (n = 150) [36,38,39], revealing moderate improvements, with moderate certainty in terms of the evidence and a favorable recommendation. Tender points were measured in four studies (n = 180) [40,41,42,43], showing moderate reductions with low inconsistency and a minimal risk of bias, leading to a moderate recommendation in favor.

Self-efficacy was investigated in two studies (n = 80) [38,41], demonstrating moderate improvements, with a low risk of bias and a favorable recommendation. The included studies exhibited a low-to-moderate risk of bias, with minimal inconsistencies and no significant concerns regarding indirectness, imprecision, or publication bias. As a result, PBMT is recommended as a non-pharmacological intervention for Fibromyalgia, with moderate-to-strong certainty in terms of the evidence across the outcomes. Further details can be found in

Table 2. Grade of recommendation (GRADE).

Outcome	1	2	3	4	5	6	7	Recommendation
Pain	6 (n = 250)	Moderate	Low	Moderate	Moderate	Not serious	Moderate	Moderate in favor
Quality of Life	5 (n = 210)	Low	Moderate	Moderate	Moderate	Not serious	Moderate	Strong in favor
Fatigue	3 (n = 150)	Moderate	Moderate	Moderate	Moderate	Not serious	Moderate	Moderate in favor
Tender Points	4 (n = 180)	Moderate	Low	Moderate	Moderate	Not serious	Moderate	Moderate in favor
Self-efficacy	2 (n = 80)	Low	Low	Moderate	Moderate	Not serious	Moderate	Moderate in favor

Summary of the findings and quality of the evidence assessed using the GRADE approach. The GRADE framework evaluates the certainty of evidence across four levels (high, moderate, low, and very low), based on factors such as the risk of bias, inconsistency, indirectness, imprecision, and publication bias: (1) number of studies (subjects), (2) risk of bias, (3) inconsistency, (4) indirectness, (5) imprecision, (6) publication bias, and (7) quality.

and Figure 2.

3.6. Data Synthesis

3.6.1. Photobiomodulation Therapy for Managing Pain Intensity in Fibromyalgia Patients

The findings from the reviewed studies highlight the efficacy of PBMT in modulating pain perception and central sensitization in individuals with Fibromyalgia. Localized PBMT has demonstrated significant effectiveness in reducing hyperalgesia associated with tender points. In a placebo-controlled trial, Gür et al. (2002) [51] applied a Class IIIb Ga-As laser (904 nm, 30 mW output) directly to tender points for 3 min per session over two weeks, resulting in a pain reduction from 3.09 to 1.27 (p < 0.05). Similarly, Ates et al. (2019) [47] investigated the effects of ten PBMT sessions in Fibromyalgia patients using a Class IIIb laser system, reporting a decrease in pain intensity from 6.9 to 3.5 (p < 0.001), reinforcing its role in targeted pain modulation.

Within localized applications, Ribeiro et al. (2023) [40] introduced a novel PBMT approach incorporating static magnetic fields (PBMT-sMF) via the FibroLux™ system, which yielded the most significant pain reduction among the reviewed studies. The intervention, using 905 nm pulsed lasers, 850 nm infrared LEDs, and 630 nm red LEDs with a power output of 50 mW per laser diode, resulted in a VAS score decrease from 80.64 to 37.80 (p < 0.0001). The treatment protocol involved direct skin contact at tender points for 120 s per site, delivering 60 J per region, administered three times per week, over three weeks. Additionally, this intervention significantly reduced the number of tender points, from 15.29 to 7.29 (p < 0.0001), suggesting a substantial impact on central sensitization mechanisms.

Beyond localized applications, whole-body PBMT has also been extensively studied for its systemic analgesic effects in Fibromyalgia syndrome. This modality involves the use of full-body light beds that emit red to near-infrared light (typically 660–850 nm) across the entire body, aiming to produce widespread biological effects through uniform tissue irradiation. In a single-arm feasibility study, Fitzmaurice et al. (2023) [36] evaluated the effects of 18 whole-body PBMT sessions over 6 weeks using the NovoTHOR^® system (660–850 nm, total power output of 967 W), reporting a VAS pain reduction from 7.4 to 3.9 (p < 0.001), with improvements maintained at a 24-week follow-up. Similarly, Navarro-Ledesma et al. (2023) [38] conducted a triple-blinded, randomized controlled trial using the same NovoTHOR^® system, applying near-infrared and red-light therapy (660–850 nm, power density ~40 mW/cm²) in 12 sessions, over 4 weeks. Their findings demonstrated a VAS pain score reduction from 7.2 to 4.1 (p < 0.001), with effects persisting at a 2-week follow-up, reinforcing the sustained efficacy of whole-body PBMT beyond the active treatment phase.

In addition to pain relief, PBMT has been shown to improve PPT in Fibromyalgia patients. Navarro-Ledesma et al. (2022) [42] reported significant increases in PPT at multiple anatomical sites, including the occiput (p = 0.039), lower cervical region (p = 0.035), and trapezius muscle (p = 0.037), further supporting its role in central desensitization.

3.6.2. Photobiomodulation Therapy for Managing QoL in Fibromyalgia Patients

Localized PBMT has shown moderate improvements by targeting tender points and modulating central sensitization mechanisms in Fibromyalgia. However, its effects on broader functional outcomes remain inconsistent. In a randomized, single-blinded trial, Ates et al. (2019) [47] assessed the impact of ten PBMT sessions on QoL in Fibromyalgia patients. While the intervention led to a significant reduction in pain intensity (a reduced VAS from 6.9 to 3.5, p < 0.001), no significant differences in QoL measures were observed when compared to local anesthetic injections.

Similarly, a double-blinded RCT by Panton et al. (2013) [50] investigated Class IV laser therapy (LiteCure^® LCT-1000, 810 nm and 980 nm, 10 W, 7 min per session, two times for 4 weeks) applied to seven tender points. The study reported a moderate reduction in Fibromyalgia Impact Questionnaire (FIQ) scores from 62 to 55 (p < 0.05); however, the improvement in QoL was less pronounced than that observed in whole-body PBMT interventions.

In contrast, whole-body PBMT has demonstrated more substantial and sustained improvements in QoL for Fibromyalgia patients. Fitzmaurice et al. (2023) [36] conducted a single-arm feasibility study evaluating whole-body PBMT over 18 sessions across 6 weeks using the NovoTHOR^® full-body PBMT system (660–850 nm, 967 W total power output, 25.2 J/cm² fluence, 20 min per session). The study reported a significant improvement in FIQR scores from 63.2 to 45.6 (p < 0.001), with benefits sustained at 24 weeks, suggesting long-term efficacy in regard to both functional and psychological well-being.

Similarly, in a triple-blinded, randomized controlled trial, Navarro-Ledesma et al. (2023) [38] administered whole-body PBMT (12 sessions, three times per week, 20 min per session) using the NovoTHOR^® system, delivering near-infrared and red-light therapy (660–850 nm, power density ~40 mW/cm²). This intervention resulted in a significant improvement in SF-36 QoL scores from 38.1 to 55.4 (p < 0.001), with effects persisting at a 2-week follow-up, reinforcing the sustained impact of PBMT on Fibromyalgia-related disability. Further supporting these findings, Navarro-Ledesma et al. (2022) [41] demonstrated that whole-body PBMT improved FIQR scores from 62.5 to 47.3 (p < 0.001), confirming its effectiveness in enhancing physical, emotional, and functional aspects of a patient’s daily life.

Additionally, the combination of PBMT with exercise has shown synergistic effects in improving a patient’s QoL. In a double-blinded RCT, Vassão et al. (2024) [35] applied PBMT to 18 muscle groups (810 nm, 100 mW, 4 J per point, three times per week for 12 weeks) in conjunction with an aerobic exercise program. The study reported a significant increase in SF-36 scores from 38.4 to 55.7 (p < 0.05), suggesting that PBMT enhances the benefits of physical activity in Fibromyalgia patients. Further details are available in Figure 3.

3.6.3. Photobiomodulation Therapy for Managing Fatigue in Fibromyalgia Patients

PBMT has resulted in a significant reduction in fatigue symptoms among Fibromyalgia patients, as supported by multiple clinical trials. In this regard, Fitzmaurice et al. (2023) [36] conducted a single-arm feasibility study assessing whole-body PBMT over a 6-week period in n = 21 Fibromyalgia patients. The study reported a substantial decrease in fatigue levels, with scores dropping from 5.9 (SD = 1.5) to 3.2 (SD = 1.4) (p < 0.001), suggesting that PBMT may enhance energy levels and overall vitality, thereby counteracting the chronic exhaustion characteristic of Fibromyalgia.

Similarly, Gür et al. (2002) [51] conducted a single-blinded, placebo-controlled trial, applying localized PBMT using a Class IIIb Ga-As laser (904 nm, 3 min per session over 2 weeks) to Fibromyalgia tender points. The study revealed a significant reduction in fatigue scores, decreasing from 3.09 (SD = 0.81) to 1.36 (SD = 1.17) (p < 0.05), reinforcing the efficacy of targeted PBMT in mitigating fatigue-related symptoms. Additionally, Navarro-Ledesma et al. (2023) [38] reported improvements in self-efficacy related to fatigue, with scores increasing from 18.2 to 22.7 (p = 0.01).

3.6.4. Photobiomodulation Therapy for Managing the Psychological Status in Fibromyalgia Patients

Psychological factors such as kinesiophobia, the fear of movement due to anticipated pain, and self-efficacy, defined as an individual’s confidence in their ability to manage their symptoms or perform tasks, appear to be among the most significantly impacted symptoms by PBMT. Navarro-Ledesma et al. (2023) [38] conducted a triple-blinded, randomized controlled trial evaluating whole-body PBMT, using the NovoTHOR system, over a 4-week period. The study reported a notable reduction in kinesiophobia, with Tampa Scale for Kinesiophobia (TSK-11) scores decreasing from 32.5 to 24.3 (p < 0.001), an improvement that persisted at follow-up. Additionally, self-efficacy significantly increased, with scores rising from 18.2 to 22.7 (p = 0.01), suggesting that PBMT may enhance patients’ confidence in managing their condition. However, no significant effects were observed in terms of pain catastrophizing, indicating that while PBMT influences movement-related fear and confidence, its impact on cognitive pain-processing mechanisms remains unclear.

Anxiety and emotional well-being also demonstrate responsiveness to light-based interventions. Green light-filtering eyeglasses, as explored in a randomized controlled trial by Nelli et al. (2023) [39], represent a novel, non-invasive visual approach. Their use led to a significant reduction in anxiety levels, with PROMIS-57 Anxiety Subscale scores decreasing from 22.1 to 18.3 (p = 0.03). Notably, this improvement was accompanied by a reduction in opioid consumption, suggesting that such interventions may support both emotional regulation and decreased pharmacological dependence. Although the precise mechanisms remain under investigation, exposure to green light has been shown to modulate activity in brain regions involved in emotional processing and pain modulation, such as the amygdala, hypothalamus, and prefrontal cortex, potentially influencing both affective states and opioid-related behaviors [52].

3.6.5. Photobiomodulation Therapy for Managing the Physiological Status in Fibromyalgia Patients

Recent research has explored the effects of PBMT on the physiological parameters associated with Fibromyalgia. Navarro-Ledesma et al. (2022) [42] documented significant improvements in muscle elasticity, as measured through elastography. Notably, reductions in muscle stiffness were observed in the trapezius and forearm distal dorsal third regions (p < 0.001), suggesting that PBMT may help alleviate muscle tension and improve tissue flexibility, which are commonly impaired in Fibromyalgia patients.

Additionally, PBMT has shown potential in regard to addressing sleep disturbances, a prevalent issue in Fibromyalgia. Choi et al. (2021) [44] reported that PBMT led to significant improvements in sleep quality, with sleep disturbance scores decreasing from 4.8 to 2.9 (p < 0.001). These findings indicate that PBMT may positively influence circadian rhythm regulation, leading to improved sleep patterns and overall rest quality. Given the critical role of sleep dysfunction in Fibromyalgia symptomatology, these results further support the integration of PBMT as a complementary approach in Fibromyalgia management.

4. Discussion

Our findings confirm that PBMT effectively reduces pain intensity in Fibromyalgia, with both localized and whole-body applications demonstrating significant analgesic effects. Localized PBMT specifically targets hyperalgesia at tender points, resulting in significant reductions in pain scores [47,53]. In contrast, whole-body PBMT provides systemic and sustained pain relief [54], with studies reporting prolonged reductions in VAS scores during follow-ups [36]. These findings align with evidence supporting PBMT’s role in modulating central sensitization [55] and reducing neurogenic inflammation [56,57].

The analgesic mechanisms of PBMT in patients with Fibromyalgia are multifactorial. They are primarily attributed to its ability to downregulate key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) [58,59], which play a central role in the maintenance of chronic pain and systemic inflammation. Additionally, PBMT has been shown to enhance local microcirculation, thereby promoting oxygen and nutrient delivery to damaged tissues and facilitating tissue repair and recovery [60]. Moreover, recent evidence suggests that PBMT can modulate the activity of glial cells in the central nervous system, which are involved in the amplification and persistence of pain through neuroinflammatory pathways [61,62]. By attenuating glial activation, PBMT may help reduce central sensitization and mitigate neuroinflammation.

Beyond its analgesic effects, PBMT has also shown promise in regard to reducing fatigue, particularly through its impact on mitochondrial function and cellular metabolism. This effect is mediated by the absorption of photons by specific intracellular chromophores, such as CCO, which are located within the mitochondrial respiratory chain [63,64,65]. Upon photon absorption, these chromophores facilitate the conversion of light energy into biochemical energy, triggering a cascade of events that lead to increased mitochondrial membrane potential, enhanced ATP production, and improved cellular respiration [66,67,68]. As a result, PBMT can enhance bioenergetic efficiency, which may help alleviate fatigue symptoms commonly reported by these patients.

Additionally, PBMT has been shown to modulate mitochondrial membrane potential and regulate the production of reactive oxygen species (ROS), thereby promoting the redox balance and reducing oxidative stress [69,70]. Rather than suppressing ROS entirely, PBMT induces a transient and controlled increase in ROS levels, which function as secondary messengers in essential cellular signaling pathways. This mild oxidative stimulus activates protective mechanisms and contributes to long-term reductions in oxidative damage, underscoring the importance of dose-dependent effects. Furthermore, PBMT increases membrane permeability, enhancing ion transport across the cytoplasmic membrane and supporting cellular homeostasis [71,72]. It also stimulates oxidative enzymes, particularly CCO, thereby improving mitochondrial respiration and ATP synthesis [73,74].

Importantly, concerns regarding potential neurotoxicity due to ROS accumulation are not supported by current preclinical or clinical evidence. On the contrary, at therapeutic dosages, PBMT promotes mitochondrial function without inducing structural or functional damage to sensory neurons. Clinical trials consistently report significant pain relief without any signs of neuropathic complications, suggesting that ROS production under PBMT acts as a beneficial signaling mechanism rather than a cytotoxic insult [69,70]. Nevertheless, given the biphasic nature of PBMT responses, careful parameter selection remains essential to ensure efficacy and safety.

Furthermore, PBMT modulates mitochondrial dynamics, particularly the processes of fission and fusion, which are essential for preserving mitochondrial integrity, optimizing ATP production, and adapting to cellular stress. Through this form of regulation, PBMT contributes to improved metabolic stability and energy efficiency [64,65]. Its anti-inflammatory effects further enhance cellular energy metabolism by reducing neuroinflammatory mediators and mitigating oxidative damage, which are closely linked to fatigue in chronic conditions [66,70].

Moreover, PBMT promotes mitochondrial biogenesis, leading to an increase in both the number and functional capacity of mitochondria within cells [63,72]. In parallel, it enhances microcirculation via nitric oxide synthase-dependent pathways, promoting vasodilation and improved local blood flow [69,71]. Notably, PBMT modulates capillary-level microvascular responses, where interindividual variability may partially account for differences in clinical outcomes [73,74].

PBMT has also demonstrated significant improvements in the patient’s QoL, particularly when applied as a whole-body treatment. Studies have reported sustained enhancements in FIQR and SF-36 scores [36], likely due to PBMT’s effects on autonomic regulation, mitochondrial function, and systemic inflammation modulation [35,75]. Whole-body PBMT positively influences the autonomic nervous system (ANS) by restoring the sympathetic-parasympathetic balance, reducing heart rate variability disruptions, and improving vagal tone factors frequently altered in Fibromyalgia [63,70,76]. Additionally, its ability to enhance mitochondrial bioenergetics and ATP synthesis contributes to increased cellular resilience and energy availability, helping to alleviate fatigue and systemic dysfunction [77,78].

In contrast, localized PBMT exhibits only moderate benefits, with some studies reporting no significant differences compared to conventional treatments, such as local anesthetic injections [47]. This limited impact on the patient’s QoL may be attributed to its primary focus on localized pain relief without addressing the broader systemic dysfunctions often present in Fibromyalgia, including ANS dysregulation and neuroinflammation [43,65]. Conversely, whole-body PBMT appears to exert neuromodulatory effects by modulating neurotransmitter release and reducing neurogenic inflammation, which may contribute to improvements in sleep quality [79,80] and cognitive performance [44,61,81,82]. Additionally, patients frequently report increased motivation and a subjective restoration of their baseline well-being, potentially linked to PBMT’s capacity to modulate neurotrophic factors and enhance synaptic plasticity [68,77,83,84].

Beyond its physiological and analgesic benefits, PBMT has demonstrated positive psychological effects, including reductions in kinesiophobia and improvements in self-efficacy [38,40]. These findings align with previous research suggesting that PBMT enhances patient engagement in neurological disorder rehabilitation and daily activities [85,86]. However, no significant effects on pain catastrophizing have been observed, suggesting that while PBMT positively influences movement-related fear, its impact on cognitive pain-processing mechanisms remains uncertain [41,45]. The potential mechanisms underlying these psychological benefits include PBMT-induced modulation of cerebral blood flow [87,88,89] and cortical excitability [90,91] in brain regions associated with pain perception and autonomic regulation [38,92,93].

PBMT has also been shown to improve key physiological parameters, particularly muscle elasticity [42,45] and sleep quality [44,94]. Studies report significant reductions in muscle stiffness following PBMT [45], indicating enhanced tissue flexibility and relief of muscle tension [95,96,97], both commonly impaired in Fibromyalgia patients [42]. Furthermore, PBMT has demonstrated potential in alleviating sleep disturbances, with research indicating improvements in sleep quality and circadian rhythm regulation [44,98]. These findings are consistent with evidence supporting PBMT’s role in modulating inflammatory pathways [99] and restoring autonomic nervous system balance [100]. The physiological mechanisms underlying these effects likely involve cytokine modulation [101], systemic inflammation reduction [27,102,103], and enhanced vagal tone regulation [104,105], ultimately contributing to improved neuromuscular function and sleep homeostasis [42].

4.1. Limitations

Despite offering relevant insights into the potential role of PBMT in the management of Fibromyalgia, this systematic review presents several limitations that should be acknowledged. First, the substantial heterogeneity in the study designs, PBMT protocols, and outcome measures, limited the feasibility of conducting a meta-analysis. Variations in wavelengths, dosimetry, treatment durations, and session frequencies across the studies hinder direct comparisons and synthesis of the therapeutic effects.

Second, most included trials were characterized by relatively small sample sizes, which may limit the statistical power and reduce the generalizability of the findings. Third, restricting the inclusion to studies published in English introduces a potential language bias, potentially excluding relevant research published in other languages.

Fourth, the short follow-up periods reported in many studies impair the assessment of the long-term effects and safety of PBMT. Additionally, a high or unclear risk of bias was identified in several trials, often due to incomplete blinding, the absence of intention-to-treat analysis, and limited reporting of adverse events, factors that compromise the overall reliability of the evidence.

Finally, the current absence of mechanistic clarity regarding how PBMT exerts its effects in Fibromyalgia, coupled with the lack of translational experimental models capable of reproducing the condition’s multifactorial symptomatology, continues to challenge efforts to elucidate its therapeutic pathways. These limitations underscore the urgent need for large-scale, methodologically robust randomized controlled trials with standardized reporting, longer term follow-up, and deeper exploration of potential mechanisms of action.

4.2. Recommendations for Clinical Practice

This review supports the use of PBMT as an adjunct in Fibromyalgia treatment. Most studies employed devices using specific wavelengths between 630–850 nm, particularly 660 nm (red) and 808–850 nm (NIR-I), known for their effective tissue penetration. Single-wavelength systems, especially in the 800–850 nm range, showed the most consistent results. Although NIR-II wavelengths allow deeper penetration, they were not used in the reviewed studies and cannot yet be recommended.

Furthermore, both localized and whole-body PBMT applications yielded positive outcomes. Localized treatments typically targeted tender points, such as the trapezius or cervical region, while whole-body devices, like NovoTHOR^® beds, provided broader systemic effects. The latter approach appeared to produce more sustained improvements in pain and quality of life, likely due to its influence on nociceptive pathways and autonomic regulation. Consequently, whole-body PBMT may be preferred, when available, particularly for patients with widespread symptomatology.

Moreover, standard treatment protocols generally involved two to three sessions per week over a period of 4 to 12 weeks, delivering doses between 4 and 60 joules per site, or following manufacturer-specific guidelines. Given PBMT’s favorable safety profile and non-invasive nature, its combination with aerobic or resistance exercise is encouraged, as this may enhance clinical outcomes related to pain modulation, physical function, and psychological well-being. Such combinations align with contemporary recommendations for multimodal management of Fibromyalgia syndrome.

In order to ensure the effectiveness and individualization of care, clinicians should monitor patient progress using standardized assessment tools. Instruments such as the VAS, the FIQ, or the SF-36 are valuable for tracking changes in pain intensity, physical capacity, and health-related quality of life, and for guiding adjustments to treatment parameters as needed. Lastly, patient education plays a pivotal role in adherence and engagement. Explaining the underlying mechanisms of PBMT, such as enhanced mitochondrial activity, increased ATP production, and reduced oxidative stress, can help demystify the intervention, reinforce its legitimacy, and foster patient commitment throughout the course of therapy.

5. Conclusions

PBMT shows potential in reducing pain, improving physical function, and enhancing quality of life in fibromyalgia patients. Whole-body applications appear to offer more consistent benefits than localized treatments. However, given the condition’s multifactorial nature, a single standardized protocol may not be universally effective. Future research should focus on standardizing methodologies and conducting large-scale, rigorous trials to optimize PBMT treatment parameters and assess its clinical efficacy.