Photobiomodulation therapy combined with a static magnetic field for chronic non-specific knee pain: protocol for a multicentre, randomised, triple-blind, placebo-controlled trial.

Knee pain represents a prevalent and growing global health concern, affecting nearly one in four adults and frequently leading to functional impairment and reduced quality of life. 1 2 Its impact is further heightened by the rising prevalence among older adults and those with osteoarthritic degeneration. 3 Among the various clinical presentations, anterior knee pain accounts for most knee-related specialist consultations, underscoring its clinical relevance and multifactorial aetiology. 4 Within this broad spectrum, a subset of individuals experience non-specific knee pain—a chronic discomfort without an identifiable structural or pathological cause. 5 This condition is often associated with patellar tendinopathy, 6 synovitis typically identified in the suprapatellar pouch, 7 prepatellar bursitis 8 or mild ligament sprains, 9 further reflecting the overlapping and complex nature of knee pain syndromes. Although the term lacks a universally accepted definition, it generally encompasses patients whose pain cannot be attributed to specific diagnoses such as meniscal tears, ligament injuries or osteoarthritis. The absence of a clear aetiology complicates both diagnosis and management, highlighting the need for improved characterisation and evidence-based treatment strategies for non-specific knee pain. 5 Given the complex and often non-specific nature of knee pain, its clinical management remains challenging. Consequently, a wide range of therapeutic modalities have been investigated to alleviate pain and promote tissue repair. Conventional interventions include therapeutic exercise, extracorporeal shockwave therapy, taping and ultrasound therapy. However, the effectiveness of many of these approaches remains inconclusive, with inconsistent evidence supporting their long-term benefits. 10 – 13 Corticosteroid injections are frequently prescribed but typically provide only temporary or modest relief, 14 while non-steroidal anti-inflammatory drugs may reduce pain in the short term without addressing the underlying pathology. 15 Among non-invasive conservative approaches, photobiomodulation therapy (PBMT) has emerged as a promising modality shown to enhance tendon and ligament repair and relieve knee pain across a variety of musculoskeletal conditions. 16 – 21 PBMT is a non-invasive technique that uses low-level light to stimulate cellular activity, thereby promoting tissue healing, modulating inflammation and relieving pain. 22 23 The combination of PBMT with a static magnetic field (PBMT-sMF) has gained increasing scientific attention for its potential to amplify the biological effects of light therapy. 24 25 Experimental and clinical evidence suggests that PBMT-sMF can facilitate tissue repair, reduce oxidative stress and modulate inflammatory processes. Studies in musculoskeletal conditions—such as tendinopathies, joint pain and muscle damage—indicate that the combined action of light and magnetic fields provides superior analgesic and functional outcomes compared with placebo. 26 – 28 Despite these encouraging findings, robust clinical evidence on the efficacy of PBMT-sMF for non-specific knee pain remains limited. Moreover, the scarcity of evidence for any specific treatment for this highly prevalent condition underscores the need for well-designed randomised controlled trials. Therefore, this study aims to evaluate the effects of PBMT-sMF, compared with placebo, on pain intensity, prostaglandin E₂ (PGE₂) concentrations, knee function and treatment satisfaction in patients with chronic non-specific knee pain.

Ethical approval was granted by the Research Ethics Committee of Irmandade da Santa Casa de Misericórdia de Porto Alegre (ISCMPA; approval number 5.767.644). All procedures will be conducted in accordance with the Declaration of Helsinki, and written informed consent will be obtained from all participants before enrolment. An example of the participant informed consent form is provided in online supplemental material 1 . Neither participants nor the public will be involved in the design, recruitment or conduct of this study. Personal information from potential and enrolled participants will be collected, stored and managed in accordance with applicable data protection regulations, with access restricted to authorised research personnel, and will be deidentified prior to analysis to ensure confidentiality before, during and after completion of the trial. Any important protocol modifications will be submitted for approval to the relevant Research Ethics Committee and updated in the ClinicalTrials.gov registry, and will be promptly communicated to investigators, study personnel, and participants, as appropriate. A summary of the principal findings will be sent to participants via email. Broader dissemination of the study outcomes will take place through peer-reviewed international journal publications and presentations at both national and international conferences.

This study is a superiority, multicentre, randomised, placebo-controlled, triple-blind clinical trial (with blinding of patients, therapists and assessors), prospectively registered at ClinicalTrials.gov ( NCT05830344 ). This study will be conducted at Santa Casa de Misericórdia de Porto Alegre, Rio Grande do Sul, Brazil, and at the Laboratory of Phototherapy and Innovative Technologies in Health, in São Paulo, Brazil. A consecutive sample of eligible participants will be recruited from the participating centres. Potential participants will be identified among patients currently receiving treatment for chronic musculoskeletal knee pain, those seeking care at the participating sites or individuals responding to recruitment materials, if necessary. Eligibility screening will be conducted by trained researchers according to the predefined inclusion and exclusion criteria. Expenses related to study participation, including transportation and light meals, will be reimbursed; however, no financial or other incentives will be offered for participation in the study. Eligible participants will be adults aged between 18 and 50 years, of any sex, who are fluent in Portuguese. Participants must present unilateral, primary knee pain, located either in the right or left knee, with a self-reported average of pain intensity of 50 mm or higher on a 0–100 mm Visual Analogue Scale (VAS) for the affected knee and less than 20 mm for the contralateral knee. The knee pain must be chronic and episodic, characterised by recurring episodes over regular or irregular intervals for a minimum of 3 months. The pain must be of benign musculoskeletal origin, including tendinopathies, synovitis, bursitis, strain or sprain of non-traumatic aetiology, as determined by the principal investigator. Diagnosis must be confirmed by a qualified and licensed medical practitioner within the previous 2 years, supported by relevant medical documentation. Where available, previous imaging records (eg, X-ray, MRI or CT scans) should demonstrate muscle or ligament injury and exclude degenerative joint disorders. A relevant medical history consistent with one of the eligible aetiologies, combined with a physical examination demonstrating increased pain during range of motion and/or pain or weakness during knee extension, flexion or gait, will be required for inclusion. Participants must also agree to maintain their usual pain management regimen, as established at baseline. Medications and therapies already in use at enrolment may be continued; however, no new pharmacological or non-pharmacological interventions for pain or inflammation may be initiated during the study period. Participants will be excluded if they have undergone previous surgical procedures on the target knee or present with neurological deficits, peripheral neuropathy, rheumatoid arthritis, hip or ankle disorders, congenital or acquired lower-limb deformities or secondary orthopaedic conditions that could influence study outcomes. Participants will also be excluded if they have received local corticosteroid or botulinum toxin injections, chiropractic treatment or acupuncture within 30 days prior to enrolment. Additional exclusion criteria include current chronic pain syndromes (such as fibromyalgia, endometriosis or diabetic neuropathic pain), active cancer or cancer treatment within the past 6 months, significant cardiac conditions (including chronic heart failure or pacemaker use), active infection or trauma in the treatment area, or any contraindication or hypersensitivity to light therapy. Pregnant or breastfeeding women or those intending to become pregnant during the trial will not be eligible. Women of childbearing potential must agree to use reliable contraception throughout the study period. Individuals with severe psychiatric disorders (such as schizophrenia or dementia), recent psychiatric hospitalisation or cognitive impairments that could compromise informed consent or data reliability will also be excluded. Finally, any medical condition or ongoing medication use that, in the opinion of the principal investigator, may interfere with the study intervention or outcome assessments will constitute grounds for exclusion. A simple randomisation sequence with a 1:1 allocation ratio will be generated using the website Random.org. Based on this sequence, the PBMT-sMF devices will be preprogrammed in either active or placebo mode prior to participant enrolment. The randomisation process and device programming will be conducted by an investigator who will not be involved in the treatment sessions or outcome assessments. To ensure allocation concealment, consecutively numbered, sealed and opaque envelopes will be used to assign participants to their respective groups. The PBMT-sMF device will emit identical operational sounds and visual indicators in both the active and placebo modes and will not produce any perceptible heat or thermal sensation. 29 The super-pulsed 905 nm laser diodes, 875 nm infrared LEDs and the sMF will be deactivated. To maintain the appearance of light emission and ensure participant blinding, the red 640 nm LEDs will remain illuminated but will operate at a minimal output of 1 mW (mean power per diode), thereby ensuring that no therapeutically meaningful energy is delivered. Consequently, the total energy emitted per irradiation site will be less than 1 J. These characteristics will allow the study to maintain triple blinding, ensuring that participants, therapists and outcome assessors remain unaware of group allocation throughout the intervention period. At the end of the trial, the success of blinding will be evaluated by asking participants, therapists and assessors to guess each participant’s treatment assignment. Participants will receive either active or placebo PBMT-sMF three times per week, with 1–2-day intervals between sessions, over a 4-week period, totalling 12 treatment sessions. Participants will be required to complete a minimum of nine treatment sessions to be considered compliant with the intervention protocol. To accommodate occasional missed appointments, the treatment series may be extended, if necessary, but must be completed within a maximum period of 5 weeks. Both interventions will be administered using the PainAway 2 Laser (Multi Radiance Medical, Solon, Ohio, USA). The intervention protocols are described below. Active PBMT-sMF: The PainAway 2 Laser (Multi Radiance Medical) combines a super-pulsed infrared laser (905 nm), three infrared LEDs (850 nm) and three red LEDs (640 nm). PBMT-sMF will be applied to five predetermined anatomical sites around the target knee: (1) superior and lateral to the patella, adjacent to the quadriceps tendon insertion; (2) superior and medial to the patella, near the medial quadriceps tendon insertion; (3) lateral to the midline at the lateral pole of the patella, close to the vastus lateralis insertion; (4) inferior pole (apex) of the patella, at the origin of the patellar tendon and (5) medial to the midline at the medial pole of the patella, near the vastus medialis insertion ( figure 1 ). Each site will receive an energy dose of 8.06 J for 25 s, resulting in a total energy delivery of 40.3 J per treatment session. The PBMT-sMF parameters are based on a previously published study. 21 Table 1 provides a detailed description of the irradiation parameters. Placebo: The placebo PBMT-sMF procedure will mirror the active intervention in terms of device configuration and irradiation sites. However, the therapeutic components of the device will be deactivated in the placebo mode. To preserve participant blinding, the device will maintain the appearance of normal operation without delivering a clinically meaningful therapeutic dose. LED, light-emitting diodes; PBMT-sMF, photobiomodulation therapy combined with static magnetic field. The primary outcome will be the degree of pain intensity, assessed at the end of the treatment period (4 weeks). Pain will be measured using a 100 mm horizontal VAS, on which participants will indicate their perceived pain along a line ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). Participants will be instructed to rate their average pain intensity during the previous 7 days. Therefore, the post-treatment assessment is intended to capture participants’ overall pain experience during the final week of the intervention, thereby reflecting the cumulative response to the complete treatment course rather than pain experienced immediately after the final treatment session. The secondary outcomes will include biochemical, functional and patient-reported measures, namely PGE₂ concentrations, subjective knee function, patient satisfaction and safety (adverse events (AEs) and co-interventions). These outcomes will be evaluated at the end of the treatment period and reassessed 1 week after completion of the intervention. Pain intensity will be measured only at the 1-week follow-up, using the same VAS procedure described for the primary outcome. PGE₂ concentrations will be determined using an ELISA with a commercial kit, following the manufacturer’s protocol (R&D Systems, Minnesota, USA). Venous blood samples will be collected by a qualified nurse from the antecubital vein, centrifuged at 3000 rpm for 20 min 1 hour after collection, and analysed using a spectrophotometer set at 450 nm with a reference wavelength of 570 nm. The results will be expressed in pg/μL. Subjective knee function will be assessed using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, a validated questionnaire comprising 18 items across three domains: (1) symptoms such as pain, stiffness, swelling, locking/catching and giving way; (2) sports and daily activities and (3) current knee function compared with preinjury status, which is not included in the total score. The overall score will be obtained by summing the item responses and converting the raw total to a normalised value ranging from 0 to 100, where 0 represents severe symptoms and poor function, and 100 indicates the absence of symptoms and normal function. 30 31 Patient satisfaction with the overall outcome will be evaluated using a 5-point Likert scale, where 1 corresponds to ‘very dissatisfied’ and 5 to ‘very satisfied’. The possible responses will include: (1) very dissatisfied, (2) dissatisfied, (3) neutral (neither satisfied nor dissatisfied), (4) satisfied and (5) very satisfied. AEs and cointerventions: Safety will be monitored throughout the study by systematically recording any AEs. Participants will be instructed to document any side effects, discomfort or unexpected symptoms in a daily logbook during both the treatment and follow-up phases. This logbook will also record any co-interventions, such as the use of additional medications or therapies for knee pain management. All reported data will be reviewed to evaluate the overall safety and tolerability of the intervention. Pain intensity will be reassessed 1 week after the end of the treatment using the same VAS procedure described for the primary outcome. The study will be conducted in five sequential phases: Preprocedure phase: Eligible participants will provide written informed consent and will be randomly allocated to either the active or placebo group. They will then complete a 2-week pain management stabilisation phase, following an individualised rescue pain management plan developed with the principal investigator. Daily medication use and pain intensity will be recorded in a participant diary. Participants will be required to maintain their existing pain management routines, restricted to medications and therapies already in use at enrolment, with no new interventions permitted. Pain intensity will be assessed on the final 3 days of this phase using a 0–100 mm VAS. Preprocedure assessment phase: Before treatment initiation, eligibility will be reconfirmed through review of adherence to the individualised regimen and verification that the 3 day average VAS pain score remains ≥50. Baseline demographic, clinical and outcome data will also be collected at this stage. Procedure administration phase: Participants will receive 12 treatment sessions (three per week for four consecutive weeks), with 1–2-day intervals between sessions. Throughout this period, participants will continue their individualised pain management plan as needed and will record daily information on medication use, symptoms and cointerventions in their diary. Procedure administration phase measures: Within 15 min after completion of the final treatment session, postintervention assessments will be performed. These will include pain intensity, PGE₂ blood analysis, IKDC evaluation, patient satisfaction, perceived treatment allocation and AE monitoring. Postprocedure phase: The 1-week follow-up period will involve continuation of the individualised pain management plan and completion of daily diary entries to document medication use, symptoms and any AEs. At the follow-up visit, all secondary outcomes will be reassessed. A schematic representation of the study design, procedures and participant flow is presented in figure 2 . The primary analysis will be based on a responder definition, whereby individual treatment success is defined as a reduction of at least 30% in pain intensity from baseline to the study endpoint. This threshold is aligned with the recommendations of the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials which indicate that a 30% reduction represents a moderate and clinically meaningful improvement in chronic pain. 32 Responder analyses are widely used in pain research, as they provide clinically interpretable results and facilitate comparison across trials. 32 Sample size estimation was informed by a pilot study conducted by our research group including 20 participants (10 per group), in which 80% of participants in the active group and 50% in the placebo group achieved the predefined success criterion. Assuming a two-tailed test, an alpha level of 0.05 and 80% statistical power, the required sample size was calculated to be 43 participants per group. 33 Accordingly, a total of 86 participants with chronic non-specific knee pain will be recruited and randomised in a 1:1 ratio, with 43 participants allocated to each group. All analyses will follow the intention-to-treat principle, whereby participants will be analysed according to their original allocation, irrespective of treatment adherence. The statistician will remain blinded to group assignment throughout the analytical process. The distribution of continuous variables will be examined using the Shapiro-Wilk test. Normally distributed baseline and demographic variables will be compared between groups using independent two-tailed Student’s t-tests for continuous data and the χ² test for categorical variables, with Fisher’s exact test used when the expected frequency is less than five in any cell. For non-normally distributed variables, the Mann-Whitney U test will be applied. The primary outcome—defined as the proportion of participants achieving the responder criterion—will be compared between groups using the χ 2 test, with Fisher’s exact test used when appropriate. For continuous outcomes, between-group differences will be analysed using analysis of covariance, with the post-intervention value as the dependent variable, treatment group as the fixed factor, and baseline values entered as covariates. If the assumptions for parametric testing are not met, non-parametric alternatives will be used. Within-group changes over time will be analysed using the Friedman test, followed by the Wilcoxon signed-rank test where appropriate. For outcomes assessed at multiple post-baseline time points, p values will be adjusted using the Bonferroni procedure to control for multiple comparisons. Patient satisfaction responses will be dichotomised into two categories: ‘positive’ (satisfied or very satisfied) and ‘non-positive’ (neutral, dissatisfied or very dissatisfied). Between-group comparisons will be performed using the chi-squared test, with Fisher’s exact test used when appropriate. The same test will be used to evaluate differences in the frequency of co-interventions. The incidence of AEs will be compared between groups using the chi-squared test or Fisher’s exact test, as appropriate. A sensitivity analysis will be conducted if any participant included in the final sample has received an intra-articular corticosteroid or botulinum toxin injection within 90 days prior to enrolment. As the effects of these interventions may persist beyond the exclusion period and potentially influence study outcomes, the primary analyses will be repeated after excluding these participants to assess the robustness of the findings. All statistical tests will be two-sided, and a p<0.05 will be considered statistically significant. Recruitment commenced in September 2025, and the first participant was randomised in September 2025. At the time of manuscript revision, the trial is ongoing, and data collection is expected to be completed by March 2027. Given the low-risk, non-invasive nature of the intervention, the relatively short duration of follow-up, and the moderate sample size, a formal data monitoring committee will not be established for this trial. The study does not involve investigational medicinal products or high-risk procedures that would require independent external safety oversight. Trial conduct and data integrity will be overseen by the principal investigator and the coordinating research team. The funder (CNPq) will have no role in data monitoring, interim analyses, or decisions regarding continuation, modification, or termination of the trial. No formal interim analyses are planned. Given the short recruitment and intervention period, as well as the absence of anticipated serious risks associated with PBMT-sMF, stopping guidelines based on interim efficacy analyses are not considered necessary. However, if unexpected serious AEs potentially related to the intervention occur, the principal investigator will evaluate the safety data and may recommend temporary suspension or early termination of the trial. Any such decision will be communicated to the Research Ethics Committee and updated in the trial registry. Monitoring of trial conduct will be performed internally on a regular basis throughout recruitment and data collection. The coordinating investigator will review adherence to the protocol, data completeness, and AE reporting at predefined intervals. Source data verification and data entry checks will be conducted to ensure accuracy and consistency. Any protocol deviations will be documented and reported in accordance with institutional and ethical requirements. Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

This protocol describes a rigorously designed randomised, triple-blind, placebo-controlled clinical trial developed to investigate the effects of PBMT-sMF on pain intensity, PGE₂ concentrations, knee function, and treatment satisfaction in individuals with chronic non-specific knee pain. Given the high prevalence and clinical burden of knee pain, along with the scarcity of evidence-based interventions for cases without a clearly identifiable structural cause, this study aims to generate both clinical and mechanistic evidence that may inform future rehabilitation strategies. Previous research has shown that PBMT and PBMT-sMF can modulate inflammation, reduce oxidative stress, and promote tissue repair in musculoskeletal disorders such as tendinopathies, joint pain, and muscle damage. 26 – 28 However, to the best of our knowledge, only one randomised controlled trial has specifically investigated the effects of PBMT-sMF on non-specific knee pain. 21 In that study, the irradiation sites differed from those proposed in the present trial, and the evaluated outcomes were limited to pain and quality of life. The current study builds upon this earlier work by adopting a prospectively registered, multicentre, triple-blind, placebo-controlled design with clearly defined inclusion and exclusion criteria, thereby ensuring greater methodological rigour and external validity. Moreover, it applies PBMT-sMF to distinct irradiation sites and includes a broader range of clinical and biochemical outcomes—such as PGE₂ levels, knee function and treatment satisfaction—to provide a more comprehensive evaluation of therapeutic efficacy. A key strength of this trial lies in its robust methodological design, which directly addresses the limitations of previous research. The triple-blind, placebo-controlled approach—encompassing participants, therapists and outcome assessors—minimises bias and enhances internal validity. The multicentre structure increases generalisability, while prospective registration promotes transparency and reproducibility. Additionally, the use of well-defined eligibility criteria ensures a homogeneous study population, reducing potential confounders. By combining subjective and objective measures, including biochemical analysis, this trial offers a multidimensional evaluation of PBMT-sMF effectiveness. Pain intensity, knee function and patient satisfaction will provide clinically meaningful insights, whereas changes in PGE₂ concentrations may help clarify the underlying biological mechanisms. Together, these methodological advances reinforce the scientific robustness of this trial and strengthen its potential to produce high-quality evidence supporting the clinical use of PBMT-sMF for chronic non-specific knee pain. Certain limitations should also be acknowledged. The first post-treatment assessment is performed immediately after the final treatment session. However, pain intensity is assessed based on participants’ average pain during the previous 7 days, thereby reflecting the cumulative effect of treatment during the final week of the intervention rather than pain experienced immediately after the final treatment session. Nevertheless, although this approach reduces the potential influence of transient treatment effects on the primary outcome, some acute effects of the final treatment session cannot be completely excluded and should therefore be considered when interpreting the findings. In addition, some secondary outcomes may be more susceptible to acute treatment responses. Another limitation is that the follow-up period will be limited to 1 week after treatment completion, which may not capture the persistence of therapeutic effects over time. Previous evidence has suggested that the effects of PBMT may become more pronounced several weeks after the end of treatment, particularly in chronic musculoskeletal conditions. 34 Therefore, the absence of medium- and long-term follow-up assessments may limit the ability to fully characterise the temporal trajectory and durability of treatment responses, thereby restricting conclusions regarding the longer-term clinical value of the intervention. Additionally, despite careful standardisation of procedures, adherence to individualised pain management regimens may vary across participants. Finally, the study population consists of adults with chronic non-specific knee pain within a specific age range, which may limit the generalisability of the findings to other age groups or acute pain conditions. In conclusion, this trial addresses an important gap in the management of chronic non-specific knee pain by investigating a non-invasive therapeutic modality that combines photobiomodulation and sMF stimulation. The findings are expected to advance understanding of PBMT-sMF’s biological and clinical effects, contribute to the development of optimised treatment protocols and ultimately support evidence-based approaches for musculoskeletal rehabilitation.