An Introduction to Low-Level Light Therapy

  • Stuart K. Bisland
Part of the Lecture Notes in Electrical Engineering book series (LNEE, volume 12)


There have been numerous reports describing the phenomena of low-level light therapy (LLLT) within the clinic and its broad application to alleviate pain, enhance the rate of wound healing, including spinal cord injury, reduce inflammation, improve learning, bolster immunity and combat disease. Yet, despite the breadth of potential applications for which bio-stimulation may prove beneficial, there persists a dramatic ignorance in our understanding of the signal pathways that govern these effects. At the cellular level, there exist a variety of endogenous chromophores such as cytochrome c oxidase, NADPH, FAD, FMN and other factors intrinsic to the electron transport chain in mitochondria that absorb light of specific wavelength and will undoubtedly have their role in bio-stimulation, however the dose dependency of effect with regard to total light fluence and fluence rate, as well as the importance of specific subcellular targeting, remains elusive. Furthermore, the translation of cellular response(s) in vitro to in vivo needs to be expounded. Clearly, a rigorous examination of bio-stimulatory parameters as a function of cellular and tissue response is necessary if we are to attain optimized, reproducible protocolsbasedonatrue scientific rationale for using bio-stimulation as a therapeutic modality in clinic. This paper introduces a number of the challenges we now face for advancing the bio-stimulation phenomena into the scientific mainstream by highlighting our current knowledge in this field as well as some of the research that we are conducting using LLLT in combination with photodynamic therapy.


Low-level light therapy photobiomodulation cytochrome c oxidase apoptosis mitochondria laser LED 



The authors wish to acknowledge the technical assistance of Anoja Giles with culturing CNS-1 cells and Emily Pai for her work on biodynamic phototherapy. We also wish to thank Canadian Institute of Health Research for financial support.


  1. 1.
    Karu T. “Photobiology of low-power laser effects.” Health Phys. 56: 691–704 (1989).CrossRefGoogle Scholar
  2. 2.
    Maiman TH. “Stimulated optical radiation in ruby” Nature, 187: 493 (1960).CrossRefGoogle Scholar
  3. 3.
    Lee MW. “Combination 532-nm and 1064-nm lasers for noninvasive skin rejuvenation and toning.” Arch Dermatol. 139: 1265–1276 (2003).CrossRefGoogle Scholar
  4. 4.
    Maiya GA, Kumar P, Rao L. “Effect of low intensity helium-neon (He-Ne) laser irradiation on dia betic wound healing dynamics.” Photomed Laser Surg. 23: 187–190 (2005).CrossRefGoogle Scholar
  5. 5.
    Baugh WP, Kucaba WD. “Nonablative phototherapy for acne vulgaris using the KTP 532 nm laser.” Dermatol Surg. 31: 1290–1296 (2005).CrossRefGoogle Scholar
  6. 6.
    Woo WK, Jasim ZF, Handley JM. “Evaluating the efficacy of treatment of resistant port-wine stains with variable-pulse 595-nm pulsed dye and 532-nm Nd:YAG lasers.” Dermatol Surg. 30: 158–162 (2004).CrossRefGoogle Scholar
  7. 7.
    Giuliani A, Fernandez M, Farinelli M, Baratto L, Capra R, Rovetta G, Monteforte P, Giardino L, Calza L. “Very low level laser therapy attenuates edema and pain in experimental models.” Int J Tissue React. 26: 29–37 (2004).Google Scholar
  8. 8.
    Gur A, Karakoc M, Nas K, Cevik R, Sarac J, Demir E. “Efficacy of low power laser therapy in fibromyalgia: a single-blind, placebo-controlled trial.” Lasers Med Sci. 17: 57–61 (2002).CrossRefGoogle Scholar
  9. 9.
    Laakso EL, Cabot PJ. “Nociceptive scores and endorphin-containing cells reduced by low-level laser therapy (LLLT) in inflamed paws of Wistar rat.” Photomed Laser Surg. 23: 32–35 (2005).CrossRefGoogle Scholar
  10. 10.
    Ferreira DM, Zangaro RA, Villaverde AB, Cury Y, Frigo L, Piccolo G, Longo I, Barbosa DG. “Analgesic effect of He-Ne (632.8 nm) low-level laser therapy on acute inflammatory pain.” Photomed Laser Surg. 23: 177–181 (2005).CrossRefGoogle Scholar
  11. 11.
    Zalewska-Kaszubska J, Obzejta D. “Use of low-energy laser as adjunct treatment of alcohol addiction.” Lasers Med Sci. 19: 100–104 (2004).CrossRefGoogle Scholar
  12. 12.
    Nussbaum EL, Lilge L, Mazzulli T. “Effects of 630-, 660-, 810-, and 905-nm laser irradiation delivering radiant exposure of 1–50 J/cm2 on three species of bacteria in vitro.” J Clin Laser Med Surg. 20: 325–33 (2002).CrossRefGoogle Scholar
  13. 13.
    Khadra M, Kasem N, Haanaes HR, Ellingsen JE, Lyngstadaas SP. “Enhancement of bone formation in rat calvarial bone defects using low-level laser therapy.” Oral Surg Med Oral Pathol Oral Radiol Endod 97: 693–700 (2004).CrossRefGoogle Scholar
  14. 14.
    Simunovic Z. “Low level laser therapy with trigger points technique: a clinical study on 243 patients.” J Clin Laser Med Surg. 14: 163–167 (1996).Google Scholar
  15. 15.
    Chen YS, Hsu SF, Chiu CW, Lin JG, Chen CT, Yao CH. “Effect of low-power pulsed laser on peripheral nerve regeneration in rats.” Microsurgery 25: 83–89 (2005).CrossRefGoogle Scholar
  16. 16.
    Byrnes KR, Waynant RW, Ilev IK, Wu X, Barna L, Smith K, Heckert R, Gerst H, Anders JJ. “Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury.” Lasers Surg Med. 36: 171–185 (2005).CrossRefGoogle Scholar
  17. 17.
    Rochkind S, Shahar A, Nevo Z. “An innovative approach to induce regeneration and the repair of spinal cord injury.” Laser Ther. 9: 151 (1997).Google Scholar
  18. 18.
    Karu T. “Primary and secondary mechanisms of action of visible to near-IR radiation on cells.” J Photochem Photobiol B. 49: 1–17 (1999).CrossRefGoogle Scholar
  19. 19.
    Karu T, Pyatibrat LV, Afanasyeva NI. “Cellular effects of low power laser therapy can be mediated by nitric oxide.” Laser Surg Med. 36: 307–314 (2005).CrossRefGoogle Scholar
  20. 20.
    Duan R, Liu TC, Li Y, Guo H, Yao LB. “Signal transduction pathways involved in low intensity He-Ne laser-induced respiratory burst in bovine neutrophils: a potential mechanism of low intensity laser biostimulation.” Lasers Surg Med. 29: 174–178 (2001).CrossRefGoogle Scholar
  21. 21.
    Brown GC. “Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase.” Biochem Biophys Acta 1504: 46”57 (2001).CrossRefGoogle Scholar
  22. 22.
    Cooper CE. “Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector?” Trends Biochem Sci. 27: 33–39 (2002).CrossRefGoogle Scholar
  23. 23.
    Young AR. “Chromopores in human skin.” Phys Med Biol. 42: 789–802 (1997).CrossRefGoogle Scholar
  24. 24.
    Nunez SC, Nogueira GE, Ribeiro MS, Garcez AS, Lage-Marques JL. “He-Ne laser effects on blood microcirculation during wound healing: a method of in vivo study through laser Doppler flowmetry.” Lasers Surg Med. 35: 363–368 (2004).CrossRefGoogle Scholar
  25. 25.
    Karu T. “High-Tech helps to estimate cellular Mechanisms of low power laser therapy.” Laser Surg Med. 34: 298–299 (2004).CrossRefGoogle Scholar
  26. 26.
    Chakraborti T, Das S, Mondal M, Roychoudhury S, Chakraborti S. “Oxidant mitochondria and calcium: An overview.” Cell Signal 11: 77–85 (1999).CrossRefGoogle Scholar
  27. 27.
    Kujawa J, Zavodnik L, Zavodnik I, Bryszewska M. “Low-intensity near-infrared laser radiation-induced changes of acetylcholinesterase activity of human erythrocytes.” J Clin Laser Med Surg. 21: 351–355 (2003).CrossRefGoogle Scholar
  28. 28.
    Jouville LS, Pinton P, Bastianutto C, Rutter GA, Rizzuto R. “Regulation of mitochondrial ATP synthesis by calcium: Evidence for long-term metabolic priming.” PNAS. 96: 13807–13812 (1999).CrossRefGoogle Scholar
  29. 29.
    Yu W, Naim JO, McGowan H, Ippolito K, Lanzafame RJ. “Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria.” Photochem Photobiol. 66: 866–871 (1997).CrossRefGoogle Scholar
  30. 30.
    Bortoletto R, Silva NS, Zangaro RA, Pacheco MT, Da Matta RA, Pacheco-Soares C. “Mito-chondrial membrane potential after low-power laser irradiation.” Lasers Med Sci. 18: 204– 206 (2004).CrossRefGoogle Scholar
  31. 31.
    Shefer G, Partridge TA, Heslop L, Gross JG, Oron U, Halevy O. “Low-energy laser irradiation promotes the survival and cell cycle entry of skeletal muscle satellite cells.” J Cell Sci. 115: 1461–1469 (2002).Google Scholar
  32. 32.
    Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M, Whelan HT. “Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome c oxidase.” J Biol Chem. 280: 4761–4771 (2005).CrossRefGoogle Scholar
  33. 33.
    Gourley PL, Hendricks JK, McDonald AE, Copeland RG, Barrett KE, Gourley CR, Singh KK, Naviaux RK. “Mitochondrial correlation microscopy and nanolaser spectroscopy — new tools for biophotonic detection of cancer in single cells.” Technol Cancer Res Treat. 4: 585–592 (2005).Google Scholar
  34. 34.
    Zhang R, Verkruysse W, Aguilar G, Nelson JS. “Comparison of diffusion approximation and Monte Carlo based finite element models for simulating thermal responses to laser irradiation in discrete vessels.” Phys Med Biol. 50: 4075–4086 (2005).CrossRefGoogle Scholar
  35. 35.
    Wilson BC, Jacques, SL. “Optical reflectance and transmission of tissues: principles and applications.” IEEE J Quantum Elect. 26: 2186—2199 (1990).CrossRefGoogle Scholar
  36. 36.
    Kienle A, Lilge L, Patterson MS, Hibst R, Steiner R, Wilson BC. “Spatially resolved absolute diffuse reflectance measurements for non-invasive determination of the optical scattering and absorption coefficients of biological tissue.” Appl Optics. 35: 2304–2314 (1996).CrossRefGoogle Scholar
  37. 37.
    Laufer J, simpson R, Kohl M, Essenpreis M, Cope M. “Effect of temperature on the optical properties of ex vivo human dermis and subdermis.” Phys Med Biol. 43: 2479–2489 (1998).CrossRefGoogle Scholar
  38. 38.
    Evans CL, Potma EO, Puoris'haag M, Cote D, Lin CP, Xie XS. “Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy.” Proc Natl Acad Sci USA. 102: 16807–16812 (2005).CrossRefGoogle Scholar
  39. 39.
    Yang VXD, Gordon ML, Tang SJ, Marcon NE, Gardiner G, Qi B, Bisland S, Seng-Yue E, Lo S, Pekar J, Wilson BC, Vitkin IA. “High speed, wide velocity dynamic range Doppler optical coherence tomography (part III): in vivo endoscopic imaging of blood flow in the rat and human gastrointestinal tract.” Opt Express. 11: 2416–2424 (2003).CrossRefGoogle Scholar
  40. 40.
    Larsson M, Nilsson H, Stromberg T. “In vivo determination of local skin optical properties and photon path length by use of spatially resolved diffuse reflectance with applications in laser Doppler flowmetry.” Appl Optics. 42: 124–134.Google Scholar
  41. 41.
    Yang VX, Mao YX, Munce N, Standish B, Kucharczyk W, Marcon NE, Wilson BC, Vitkin IA. “Interstitial Doppler optical coherence tomography.” Opt Lett. 30: 1791–1793 (2005).CrossRefGoogle Scholar
  42. 42.
    Sun H, Mangner TJ, Collins JM, Muzik O, Douglas K, Shields AF. “Imaging DNA synthesis in vivo with 18F-FMAU and PET.” J Nucl Med. 46: 292–296 (2005).Google Scholar
  43. 43.
    Brauer M. “In vivo monitoring of apoptosis.” Prog Neuro-Psychoph. 27: 323–31 (2003).CrossRefGoogle Scholar
  44. 44.
    Czarnota GJ, Kolios MC, Hunt JW, Sherar MD. “Ultrasound imaging of apoptosis. DNA-damage effects visualized.” Methods Mol Biol. 203: 257–277 (2002).Google Scholar
  45. 45.
    Shaban H, Borras C, Vina J, Richter C. “Phosphatidylglycerol potently protects human retinal pigment epithelial cells against apoptosis induced by A2E, a compound suspected to cause age-related macula degeneration.” Exp Eye Res. 75: 99–108 (2002).CrossRefGoogle Scholar
  46. 46.
    von Lewinski F, Keller BU“Ca2, mitochondria and selective motoneuron vulnerability: implications for ALS.” Trends Neurosci. 28: 494–500 (2005).CrossRefGoogle Scholar
  47. 47.
    Leszkiewicz DN, Aizenman E. “Reversible modulation of GABA(A) receptor-mediated currents y light is dependent on the redox state of the receptor.” Eur J Neurosci. 17: 2077–2083 (2003).CrossRefGoogle Scholar
  48. 48.
    Bisland SK, Pai E, Wilson BC, “Biodynamic phototherapy: Priming cells for 5-aminolevu-linic acid-mediated photodynamic therapy. ” In preparation. Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Stuart K. Bisland
    • 1
  1. 1.Ontario Cancer InstituteUniversity Health Network, University of TorontoTorontoCanada

Personalised recommendations