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Photomodulation

Original Editor - Angeliki Chorti

Top Contributors - Angeliki Chorti and Alexandra Stead  

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Description

Definition

Photomodulation, or Photobiomodulation (PBM) / Photobiomodulation Therapy (PBMT) uses non-ionising light sources to modulate cellular activity and promote therapeutic outcomes.[1] This non-thermal, non-invasive therapeutic tool typically refers to red or near-infrared (NIR) light in the form of low-level lasers, broad-spectrum lamps, or light-emitting diode devices (LEDs) to penetrate skin and the underlying tissue.[2] Other wavelengths (e.g. blue or green light) have also been reported and investigated for their effect.[3][4][5][6][7][8][9][10]

PBM can be found in the scientific literature with various names. The use of different terminology with regards to therapeutic applications and lack of consensus of a standard name has been highlighted in the past, and some efforts have been made at an international level to standardise the use of PBM as the preferred term.[11]

Table 1 provides an overview of different terms used throughout the years for photomodulation.[11]

Table 1. Examples of terms used for photomodulation.[11]
Term
Laser biostimulation
Phototherapy
Low-level laser therapy (LLLT)
Low intensity laser therapy
Low-power laser therapy
Cold laser
Soft laser
Photobiostimulation
Photobiomodulation
Photodynamic therapy (PDT)
Optogenetics

Historical Perspective

The widespread use of light in the conservative management of patients was promoted in the 1960s. In 1967, Endre Mester at the Semmelweis University in Budapest, Hungary studied the adverse effects of laser in mice, only to find out that it actually had resulted in hair regrowth instead of cancer.[12] In 1968, Mester et al. published their findings on the effects of laser beams on hair regrowth in mice and laid the ground for further investigation on the therapeutic application of light. [13] Since then, interest in PBM has risen significantly.

Mechanism of Action

Although it is widely accepted that PBM induces physiological responses across multiple tissue types, specific mechanisms of action of PBM are not precisely understood and PBM protocols lack standardisation across the field.[1] However, primary and secondary effects are suggested to work at the molecular, cellular and as an extension, the clinical level.[1] For example, it is suggested that PBM works by stimulating cellular mitochondria (specifically mitochondrial cytochrome c oxidase- CCO); these are the body's endogenous photoreceptors, leading to other bodily effects.[1] Transcranial PBM, in the form of non-invasive brain stimulation in the prefrontal cortex of humans, demonstrated positive age-dependent changes in mitochondrial respiration, cerebrovascular oxygenation and neurocognitive function thought to arise from this effect.[14] Other proposed mechanisms of PBM action include modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1.[1][15] Cellular context and micro-environment play a role in the above mechanisms.[1] According to a 2017 study, PBM effects can be wavelength-dependent: for example, red and near-infrared wavelengths stimulate proliferation and increase ATP, in contrast to blue and green light that do the opposite in adipose-derived stem cells (ASCs).[2] They can also be dose-dependent: PBM energy density influenced cell proliferation in meniscus stem cells (MeSCs) and was mediated by biological channels when specific LED wavelengths (700-710 and 1064nm) were used.[16]

Table 2 describes the types of PBM, penetration depth according to wavelength and proposed therapeutic effects in humans. Please note that penetration depths are approximate and tissue dependent and values reflect computational modelling by Ash et al.[17]

Table 2. PBM wavelength bands, approximate penetration depth and proposed clinical applications.[17][18]
Type Wavelength Penetration Depth Proposed Therapeutic Use
Blue 400-495 nm <1 mm (Epidermis) Superficial skin treatments,[19] [20]antimicrobial applications,[21][22] neonatal jaundice,[23] adjuctive use in psychiatric disorders[24]
Green 495-570 nm ~1-3 mm (Epidermis and Papillary Dermis) Pigmentation modulation,[25] bone healing adjunct,[26] pain modulation[27][28][29]
Red 600-670 nm ~1–6 mm (Dermis) Collagen synthesis and wound healing,[30] anti-aging[31]
NIR 700-1100 nm ~5–25 mm (Subcutaneous and Superficial Muscle) Musculoskeletal pain and recovery,[32] wound healing,[33] transcranial applications[34]

Therapeutic Applications

Blue light therapy for acne.
Blue light therapy for acne.

PBM has been investigated showing promise across a wide range of clinical applications:

PBM has very few established clinical applications and many are in the preclinical phase. Evidence quality varies greatly across indications. However, regulatory recognition is evolving and examples include devices such as the FDA-approved Valeda Light Delivery System for intermediate dry age-related macular degeneration.[59]

PBM Parameters

PBM effective and safe use is largely dependent on the appropriate selection and application of treatment parameters. The World Association for Photobiomodulation Therapy (WALT) publishes condition-specific recommendations for PBM treatment and dosage (last update was in 2022). You can also find recommendations for the conduct of randomised controlled trials and systematic reviews / meta-analyses on PBM.

Contraindications and Precautions

Light therapy can be generally safe, but some contraindications and certain precautions should also be considered in clinical applications in the light of studies reporting potential adverse events.[37][60] Some generic examples include the following:

  • Active cancer: PBM should not be directly applied to cancerous tissue or the thyroid because of its potential to stimulate the metabolism and proliferation of cells that may promote cancer growth.
  • Thyroid: the thyroid gland's sensitivity to light and especially in conditions like active hyperthyroidism may hide potential dangers that need to be accounted for.
  • Photosensitising medication or conditions: some drugs like tetracyclines, antipsychotics and retinoids, and systemic conditions like lupus may lead to skin adverse reactions.
  • Pregnancy and lactation: it is best to avoid the areas of abdomen and breasts during pregancy and breastfeeding.

[37][60]

Benefit, Safety and Risks

PBM is an emerging treatment approach and sound evidence on safety and actual risks is missing together with effective condition-specific treament protocols. This is suggested in many reviews about PBM that also highlight the need for robust evidence to ensure clinical relevance, long-term benefit and safety.[40][50][58][61][62]

Resources

For more information on different types of light you can visit the following pages:

Sunlight, Outdoor Light, and Light Therapy in Disease Management

Blue Light and the Effect on Sleep

Low Level Laser Therapy

Achilles Tendinopathy Toolkit: Section E - Low Level Laser Therapy Dosage Calculation

High Power Laser Therapy

Red Light Therapy and Muscle Recovery

Noninvasive Brain Stimulation (NIBS)

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Frankowski DW, Ferrucci L, Arany PR, Bowers D, Eells JT, Gonzalez-Lima F, Lohr NL, Quirk BJ, Whelan HT, Lakatta EG. Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy. Geroscience. 2025 Jun;47(3):2777-89.
  2. ↑ 2.0 2.1 Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR. Red (660 nm) or near-infrared (810 nm) photobiomodulation stimulates, while blue (415 nm), green (540 nm) light inhibits proliferation in human adipose-derived stem cells. Sci Rep. 2017 Aug 10;7(1):7781.
  3. ↑ Serrage H , Heiskanen V , Palin WM , Cooper PR , Milward MR , Hadis M , Hamblin MR . Under the spotlight: mechanisms of photobiomodulation concentrating on blue and green light. Photochem Photobiol Sci. 2019 Aug 1;18(8):1877-1909.
  4. ↑ Martin L, Porreca F, Mata EI, Salloum M, Goel V, Gunnala P, Killgore WDS, Jain S, Jones-MacFarland FN, Khanna R, Patwardhan A, Ibrahim MM. Green Light Exposure Improves Pain and Quality of Life in Fibromyalgia Patients: A Preliminary One-Way Crossover Clinical Trial. Pain Med. 2021 Feb 4;22(1):118-130.
  5. ↑ Zhang Y, Wang Z, Cao J, Dong Y, Chen Y. A Green and Blue Monochromatic Light Combination Therapy Reduces Oxidative Stress and Enhances B-Lymphocyte Proliferation through Promoting Melatonin Secretion. Oxid Med Cell Longev. 2021 Mar 19;2021:5595376.
  6. ↑ Ebbesen F, Vandborg PK, Donneborg ML. The effectiveness of phototherapy using blue-green light for neonatal hyperbilirubinemia - Danish clinical trials. Semin Perinatol. 2021 Feb;45(1):151358.
  7. ↑ Nelli A, Wright MC, Gulur P. Green Light-Based Analgesia - Novel Nonpharmacological Approach to Fibromyalgia Pain: A Pilot Study. Pain Physician. 2023 Jul;26(4):403-410.
  8. ↑ Baron R, Morlion B, Dahan A, Überall M, von Basum G, Wild I. A prospective, randomized, controlled, double-blind, multi-center study to evaluate the efficacy and safety of a blue light device for the treatment of chronic back pain. Front Pain Res (Lausanne). 2024 Jul 23;5:1444401.
  9. ↑ Feng Q, Chen L, Li L, Yang J, Wu J, Yue Y, Wang Z. A study of the efficacy of 500nm blue‐green light therapy on cognition, mood, and sleep in prodromal Alzheimer's disease. Alzheimers Dement. 2025 Jan 3;20(Suppl 3):e088968.
  10. ↑ Shi Z, Li S, Chen W, Yan H. The effect of blue and green light on human umbilical cord mesenchymal stem cells for promoting proliferation and wound healing. Sci Rep. 2025 Apr 28;15(1):14787.
  11. ↑ 11.0 11.1 11.2 Anders JJ, Lanzafame RJ, Arany PR. Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg. 2015 Apr;33(4):183-4.
  12. ↑ Mester E, Szende B, Tota J. Influence of laser beams on the growth of hair in mice. [A lézersugár hatása az egér szőrnövekedésére]. Kísérletes Orvostudomány, 1967; 19: 628-31. [Hungarian]
  13. ↑ Mester E, Szende B, Gärtner P. Die Wirkung der Lasstrahlen auf den Haarwuchs der Maus [The effect of laser beams on the growth of hair in mice]. Radiobiol Radiother (Berl). 1968;9(5):621-6. German.
  14. ↑ Saucedo CL, Courtois EC, Wade ZS, Kelley MN, Kheradbin N, Barrett DW, Gonzalez-Lima F. Transcranial laser stimulation: Mitochondrial and cerebrovascular effects in younger and older healthy adults. Brain Stimul. 2021 Mar-Apr;14(2):440-449.
  15. ↑ Dompe C, Moncrieff L, Matys J, Grzech-Leśniak K, Kocherova I, Bryja A, Bruska M, Dominiak M, Mozdziak P, Skiba THI, Shibli JA, Angelova Volponi A, Kempisty B, Dyszkiewicz-Konwińska M. Photobiomodulation-Underlying Mechanism and Clinical Applications. J Clin Med. 2020 Jun 3;9(6):1724.
  16. ↑ Tong J, Wu X, Wang Z, Li X, Yu Y, Zhang Z, Zheng Z, Huang T, Ma Z. Photobiomodulation stimulates mitochondrial function and cell proliferation in meniscus-derived stem cells (MeSCs) via activation of TRPV1 channel. Sci Rep. 2025 Dec 4;15(1):43131.
  17. ↑ 17.0 17.1 Ash C, Dubec M, Donne K. Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods. Lasers Med Sci. 2017; 32:1909–18.
  18. ↑ Sviridova N, Zhao T, Aihara K, Nakamura K, Nakano A. Photoplethysmogram at green light: Where does chaos arise from? Chaos, Solitons & Fractals 2018; 116:157-65.
  19. ↑ Bayat M, Albright R, Hamblin MR, Chien S. Impact of Blue Light Therapy on Wound Healing in Preclinical and Clinical Subjects: A Systematic Review. J Lasers Med Sci. 2022 Dec 17;13:e69.
  20. ↑ Prado TP, Zanchetta FC, Barbieri B, Aparecido C, Melo Lima MH, Araujo EP. Photobiomodulation with Blue Light on Wound Healing: A Scoping Review. Life (Basel). 2023 Feb 18;13(2):575.
  21. ↑ Leanse LG, Dos Anjos C, Mushtaq S, Dai T. Antimicrobial blue light: A 'Magic Bullet' for the 21st century and beyond? Adv Drug Deliv Rev. 2022 Jan;180:114057.
  22. ↑ Goh MH, Connolly JJ, Chen AF, Rabiner RA, Lozano-Calderon SA. Antimicrobial effect of blue light on antibiotic-sensitive and drug-resistant Escherichia coli: a novel isotropic optical fibre. Access Microbiol. 2025 Mar 19;7(3):000967.v3.
  23. ↑ Wu R, Wen L. Meta-analysis of the efficacy of different blue light therapy methods for neonatal jaundice. J Matern Fetal Neonatal Med. 2025 Dec;38(1):2430649.
  24. ↑ Ren L. Blue light treatment of psychiatric disorders: relationships with systemic inflammation, lipid metabolism, and clinical symptoms. BMC Psychiatry. 2025 Oct 21;25(1):1008.
  25. ↑ Mima Y, Yamada T, Omatsu J, Yamashita T, Suzuki S, Takechi T, Ichikawa M, Yamazaki K, Sato S, Yoshizaki A. Inhibitory Effect of 505 nm Green Light Emitting Diode on Melanin Synthesis in Cellular Experiments and a Human Intervention Study. Acta Derm Venereol. 2025 May 15;105:adv43441.
  26. ↑ Bao W, Zhuang J, Liu F, Hu J, Chen X, Jiang Y. Green Light Photobiomodulation: A Systematic Review of New Approaches for Treating Bone Repair. Photobiomodul Photomed Laser Surg. 2025 Dec;43(12):565-584.
  27. ↑ Martin LF, Cheng K, Washington SM, Denton M, Goel V, Khandekar M, Largent-Milnes TM, Patwardhan A, Ibrahim MM. Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain. J Pain. 2023 Mar;24(3):509-529.
  28. ↑ Qaiser H, Uzair M, Arshad M, Zafar A, Bashir S. Evaluating the Potential of Green Light Exposure on Nociception-A Mini Review. CNS Neurol Disord Drug Targets. 2024;23(6):675-9.
  29. ↑ Dai W, Zhang Y, Gu R, Zhu X, Leng Y, Ma L, Zhang M. The analgesic effect of green light on neuropathic pain: a mini-review of the literature and a proposal for future work. Front. Pain Res. 2025;6:1653186.
  30. ↑ Kuppa SS, Kang JY, Kim JY, Sa G, Park JH, Kim JH, Ha TS, Seon JK, Kim HK, Lee JB. Red-light LED therapy promotes wound regeneration by upregulating COL1A1, COL2A1, VEGF and reducing IL-1β for anti-inflammation. Lasers Med Sci. 2025 Apr 3;40(1):171.
  31. ↑ Couturaud V, Le Fur M, Pelletier M, Granotier F. Reverse skin aging signs by red light photobiomodulation. Skin Res Technol. 2023 Jul;29(7):e13391.
  32. ↑ Tripodi N, Feehan J, Husaric M, Sidiroglou F, Apostolopoulos V. The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials. BMC Sports Sci Med Rehabil. 2021 Aug 14;13(1):91.
  33. ↑ Liu J, Gopal V, Ellis B, Ray I, Pappu S, Jan YK. Effects of Near Infrared Light on Surgical Wound Healing: A Systematic Review and Meta-Analysis. Int Wound J. 2026 Feb;23(2):e70841.
  34. ↑ Trofimov AO, Kalinkina E, Medvedeva A, Volkova E, Kivenko A, Nemoto EM, Bragina OA, Bragin DE. Near-infrared light-induced transcranial photobiomodulation enhances the visual pathway's function in healthy volunteers. J Biomed Opt. 2025 Feb;30(Suppl 2):S23908.
  35. ↑ Syed SB, Ahmet I, Chakir K, Morrell CH, Arany PR, Lakatta EG. Photobiomodulation therapy mitigates cardiovascular aging and improves survival. Lasers Surg Med. 2023;55:278–93.
  36. ↑ Oliveira de Moraes LH, Buzinari TC. Photobiomodulation in cardiovascular diseases: molecular mechanisms and pharmacological approaches to enhance the therapeutics effects of light. Lasers Med Sci. 2025 Nov 3;40(1):464.
  37. ↑ 37.0 37.1 37.2 Al Balah OF, Rafie M, Osama AR. Immunomodulatory effects of photobiomodulation: a comprehensive review. Lasers Med Sci. 2025 Apr 11;40(1):187.
  38. ↑ Huang J, Chen J, Xiong S, Huang J, Liu Z. The effect of low-level laser therapy on diabetic foot ulcers: A meta-analysis of randomised controlled trials. Int Wound J. 2021 Dec;18(6):763-776.
  39. ↑ Gupta A, Keshri GK, Yadav A, Gola S, Chauhan S, Salhan AK, Bala Singh S. Superpulsed (Ga-As, 904 nm) low-level laser therapy (LLLT) attenuates inflammatory response and enhances healing of burn wounds. J Biophotonics. 2015 Jun;8(6):489-501.
  40. ↑ 40.0 40.1 Brassolatti P, de Andrade ALM, Bossini PS, Otterço AN, Parizotto NA. Evaluation of the low-level laser therapy application parameters for skin burn treatment in experimental model: a systematic review. Lasers Med Sci. 2018 Jul;33(5):1159-1169.
  41. ↑ He L, Di D, Chu X, Liu X, Wang Z, Lu J, Wang S, Zhao Q. Photothermal antibacterial materials to promote wound healing. J Control Release. 2023 Nov;363:180-200.
  42. ↑ Glass GE, Mérai A, Molnár S, Clayton P. The Use of a Proprietary Near-Infrared Laser to Enhance Wound Healing: A Preliminary Preclinical and Clinical Study. Aesthet Surg J Open Forum. 2025 Feb 5;7:ojaf009.
  43. ↑ Chhabrani A, Avinash B, Bharadwaj RS, Gupta M. Laser light: Illuminating the path to enhanced periodontal care. Photodiagn Photodyn. 2024 April; 46:104036.
  44. ↑ Glass GE. Photobiomodulation: A Systematic Review of the Oncologic Safety of Low-Level Light Therapy for Aesthetic Skin Rejuvenation. Aesthet Surg J. 2023 Apr 10;43(5):NP357-NP371.
  45. ↑ Hernández-Bule ML, Naharro-Rodríguez J, Bacci S, Fernández-Guarino M. Unlocking the Power of Light on the Skin: A Comprehensive Review on Photobiomodulation. Int J Mol Sci. 2024 Apr 19;25(8):4483.
  46. ↑ Russell MW, Rachitskaya AV. Photobiomodulation Therapy for Management of Retinal Diseases. Curr Ophthalmol Rep. 2025; 13:13.
  47. ↑ Shen Q, Guo H, Yan Y. Photobiomodulation for Neurodegenerative Diseases: A Scoping Review. Int J Mol Sci. 2024 Jan 28;25(3):1625.
  48. ↑ Sinha G. Trials begin for a new weapon against Parkinson's: light. Science. 2020 Sep 18;369(6510):1415-16.
  49. ↑ Fifel K, Videnovic A. Light Therapy in Parkinson's Disease: Towards Mechanism-Based Protocols. Trends Neurosci. 2018 May;41(5):252-54.
  50. ↑ 50.0 50.1 Wang M, Dinarvand D, Chan CTY, Bragin A, Li L. Photobiomodulation as a Potential Treatment for Alzheimer's Disease: A Review Paper. Brain Sci. 2024 Oct 26;14(11):1064.
  51. ↑ Zhang Y, Ji Q. Current advances of photobiomodulation therapy in treating knee osteoarthritis. Front Cell Dev Biol. 2023 Nov 16;11:1286025.
  52. ↑ Xia P, Fan T, Huang Y, Zheng H, Ma R, Zhou W, et al. Photobiomodulation for the treatment of knee osteoarthritis: therapeutic effects and molecular mechanism. Front. Cell Dev. Biol. 2026; 14:1744761.
  53. ↑ Gao Y, An R, Huang X, Liu W, Yang C, Wan Q. Effectiveness of photobiomodulation for people with age-related cognitive impairment: a systematic review and meta-analysis. Lasers Med Sci. 2023 Oct 16;38(1):237.
  54. ↑ Pan WT, Liu PM, Ma D, Yang JJ. Advances in photobiomodulation for cognitive improvement by near-infrared derived multiple strategies. J Transl Med. 2023 Feb 22;21(1):135.
  55. ↑ Huang X, Sun Z, Wu W, Lou L, Wang P, Wang Q,et al. Red-light photobiomodulation improves cognition and neuropsychiatric symptoms in post-stroke cognitive impairment: a randomized trial. Front. Neurol. 2025; 16:1634701.
  56. ↑ Lim L, Hosseinkhah N, Van Buskirk M, Oei K, Berk A, Pushparaj A, et al. Photobiomodulation for cognitive dysfunction (Brain Fog) in post-COVID-19 condition: a randomized double-blind sham-controlled pilot trial. eClinicalMedicine. 2026 Feb; 92:103730.
  57. ↑ Zhu Z, Zhang R, Chi Y, Li W, Gong W. Photobiomodulation effects on cognitive function - a systematic review and meta-analysis of randomized controlled trials. Lasers Med Sci. 2025 May 21;40(1):234.
  58. ↑ 58.0 58.1 de Pauli Paglioni M, Araújo ALD, Arboleda LPA, Palmier NR, Fonsêca JM, Gomes-Silva W, Madrid-Troconis CC, Silveira FM, Martins MD, Faria KM, Ribeiro ACP, Brandão TB, Lopes MA, Leme AFP, Migliorati CA, Santos-Silva AR. Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review. Oral Oncol. 2019 Jun;93:21-28.
  59. ↑ DEN230083, Valeda Light Delivery System, LumiThera, Inc. Available from: https://www.accessdata.fda.gov/cdrh_docs/reviews/DEN230083.pdf [accessed 4th May 2026]
  60. ↑ 60.0 60.1 Navratil L, Kymplova J. Contraindications in noninvasive laser therapy: truth and fiction. J Clin Laser Med Surg. 2002 Dec;20(6):341-3.
  61. ↑ Chen KY, Lee HK, Chan HC, Chan CM. Is Multiwavelength Photobiomodulation Effective and Safe for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis. Ophthalmol Ther. 2025 May;14(5):969-987.
  62. ↑ Son Y, Lee H, Yu S, Kim HJ, Park J, Woo S, Lee H, Fond G, Boyer L, Rahmati M, Smith L, López Sánchez GF, Dragioti E, Kang J, Kim T, Yon DK. Effects of photobiomodulation on multiple health outcomes: an umbrella review of randomized clinical trials. Syst Rev. 2025 Aug 6;14(1):160.
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