Condition Focus: Knee Osteoarthritis, Fibromyalgia, Tendinopathy — Broadest Evidence Synthesis
An umbrella review is the highest tier of evidence synthesis — a systematic review of systematic reviews. Son and colleagues performed this analysis across multiple health outcomes, applying both AMSTAR 2 (to assess the quality of included reviews) and GRADE (to rate the certainty of evidence) frameworks. Published in Systematic Reviews (BMC), this represents the broadest and most methodologically rigorous evidence synthesis available for PBM.
The review found moderate certainty evidence for PBM’s efficacy in reducing knee OA pain and fibromyalgia fatigue. It also identified evidence across tendinopathy and temporomandibular disorders. The pain mechanisms discussed include substance P reduction (a neuropeptide involved in pain signalling), bradykinin suppression (which contributes to pain sensitisation), and endorphin and serotonin upregulation (natural pain-modulating compounds).
The multi-mechanism pain modulation described here is relevant to gout because gout pain is not driven by a single pathway. During an acute flare, pain results from inflammatory cytokines activating nociceptors, prostaglandins sensitising pain nerve endings, substance P amplifying pain signals, and mechanical pressure from edema within the joint capsule. An intervention that modulates multiple pain pathways simultaneously — as PBM does — is better suited to this multi-pathway pain than a single-target drug.
The GRADE methodology is particularly important for clinician confidence: it categorises evidence as high, moderate, low, or very low certainty. “Moderate certainty” means further research is unlikely to change the conclusion substantially — a strong positioning statement for PBM.
G.O.A.T. for Gout Alignment:
The moderate GRADE certainty for knee OA pain strengthens the evidence framework for the G.O.A.T. Gout and OA share inflammatory pain pathways, and the multi-mechanism pain modulation (substance P, bradykinin, endorphin, serotonin) aligns with the G.O.A.T.’s approach of addressing pain through cellular modulation rather than single-pathway blockade.
Link to original research here
Editor’s note: The knee OA pain evidence reviewed here is demonstrated at the individual meta-analysis level in Oliveira et al 2024. For the substance P and bradykinin pathways referenced, the underlying cytokine modulation is detailed in PBM on OA Narrative Review 2025. The whole-body PBM trial demonstrating sustained pain relief is reported in Navarro-Ledesma et al 2022. The oxidative stress pathway that intersects with pain modulation in OA is explored in Yamada et al 2020.
Related Articles
- PBM for Knee OA Pain and Disability: Meta-Analysis – Oliveira et al 2024
- Whole-Body PBM on Pain and QoL: Triple-Blind RCT – Navarro-Ledesma et al 2022
- PBM Reduces Oxidative Stress and Inflammation in Knee OA – Yamada et al 2020
- Effects of PBM on OA from In Vivo and In Vitro Studies – Narrative Review 2025
- Effects of LLLT on Pain in Musculoskeletal Disorders: Meta-Analysis – Clijsen et al 2017
Key Takeaways
- Umbrella review — highest tier of evidence synthesis: systematic review of systematic reviews
- Moderate GRADE certainty for PBM in knee OA pain and fibromyalgia fatigue
- Multi-mechanism pain modulation: substance P↓, bradykinin↓, endorphin↑, serotonin↑
- AMSTAR 2 quality assessment of included reviews ensures methodological rigour
Study Overview
| Study Type: | Umbrella review of systematic reviews |
| Wavelength(s): | 600–1100 nm (across reviewed meta-analyses) |
| Treatment Protocol: | Varies across reviewed systematic reviews |
| Sample Size: | Multiple systematic reviews and meta-analyses pooled |
| Primary Outcome: | Moderate certainty evidence for knee OA pain and FM fatigue reduction |
Full Citation
Son Y, et al. (2025). Effects of photobiomodulation on multiple health outcomes: an umbrella review of systematic reviews and meta-analyses. Systematic Reviews, 14. View Publication
