LASER THERAPY : Photobiomodulation

[Low Intensity Laser Therapy – LILT : Low Level Laser Therapy – LLLT]
 
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Introduction

Light Absorption in the Tissues

Laser - Tissue Interaction

Dose Calculations

Clinical Applications

References

 
Introduction

The term LASER is an acronym for the Light Amplification by Stimulated Emission of Radiation. In simple yet realistic terms, the laser can be considered to be a form of light amplifier - it provides enhancement of particular properties of light energy.

 

Laser light will behave according to the basic laws of light, in that it travels in straight lines at a constant velocity in space. It can be transmitted, reflected, refracted and absorbed. It can be placed within the electromagnetic spectrum according to its wavelength/frequency which will vary according to the particular generator under consideration.

There are several aspects of laser light which are deemed to be special and are often referred to in the literature. These include monochromacity, coherence and polarisation. There remains some doubt as to exactly how essential these particular aspects of laser light are in relation to the therapeutic application of this energy form. Monochromacity is probably the most important factor, as many of the therapeutic effects have been noted in various trials with light which is non-coherent. Additionally, it is thought that the polarisation is soon lost within the tissues & may therefore be less important than was thought at first.

Therapy Lasers have several common characteristics which are summarised below.

 

Terms : Therapy lasers tend to fall into a particular category of laser light known as 3A or 3B (see below for more detail) & are often referred to as 'soft laser' or 'mid laser' sources. The terms Low Level Laser Therapy (LLLT) and Low Intensity Laser Therapy (LILT) have been adopted and most recently, a move to use the term photobiomodulation is starting to dominate the literature. In the context of this document, the terms are considered synonymous. Ohshiro & Calderhead suggest that LLLT involves treatment with a dose that causes no detectable temperature rise in the treated tissues and no macroscopically visible change in tissue structure – essentially, the energy can cause in increase in temperature and a change in tissue structure, but that is not the intention with therapy laser which is applied at levels below that needed to achieve these more overt effects (c/f surgical laser).

 

Laser vs LED and Variants

There is a lot of potentially confusing terminology out there with regards lasers, laser diodes and LED emitters. Without doing a full blast physics paper, I will try and summarise the differences:

 

True lasers came into being during the 1960’s and moved into the therapy arena by the last 1970’s early 1980’s with much of the early work carried out in Eastern Europe and the old Soviet block

 

A true laser (gas and mirrors rather than smoke and mirrors!!!)) employs a specific generation mechanism (Laser is an acronym  = Light Amplification by Stimulated Emission of Radiation). It is MONOCHROMATIC (all waves are the same wavelength) and COHERENT (all waves are exactly ‘in tune’). This combination makes it very different from light derived from any other source. Laser light is also Collimated (meaning all parts travel in one and same direction – essentially the bean is NON-DIVERGENT).

A Laser Diode essentially generates light which is MONOCHROMATIC but does NOT have absolute COHERENCE (given that the coherence is lost as soon as you push it into the tissue, it is argued that there is no point spending time, effort, energy – and thus, money) making the light coherent, only to lose that factor within fractions of a mm into the tissues). The (clinical) effects of laser and the light from a laser diode appear to be equivalent. Laser diodes are almost always the source of ‘laser’ light used in therapy. (Different authorities take slightly differing views on the true laser / laser diode differences, but that is the essentials of it)

Coherent / Non Coherent light

(from www.miridiatech.com)

An LED (Light Emitting Diode) as a generator is even less expensive – and less complex.. It is a (semiconductor) junction diode. The light it generates is not strictly speaking laser by virtue of its lack of absolute monochromasticity and coherence – i.e. the light it generates does not exhibit 2 of the critical things that makes laser light ‘different’. The light from an LED is NOT coherent and NOT collimated (i.e. it is divergent). LED’s generally considered to generate a broader band of wavelengths, though this can be narrow, it is (technically) not the same as monochromatic laser light. (The bandwidth of a usual laser diode is around or less than 0.1 nanometer, while that of regular LEDs is up to a few 10's of nanometers). The LED light generation is not achieved by stimulation – which is why it is ‘weaker’ – they talk about spontaneous rather than stimulated emission.

 

LED’s are considered ‘eye safe’ whereas lasers and laser diodes are not and eye protection is needed.

 

We effectively have a rank order in terms of ‘pureness’ with laser at the top rank, Laser Diodes in the middle and LED’s at the bottom end, well not the bottom end, because after that, we go to a domestic light bulb!

 

There have been several papers in recent years which have compared the (clinical) effects of ‘lasers’ vs LED’s. Examples include  de Abreu Chaves; et al (2014); De Castro et al (2014); Lima et al. (2017). I can not find a difference between their effects when equivalent doses are delivered.

 

Parameters : Most LLLT apparatus generates light in the Red Visible & Near Infra-red bands of the EM spectrum, with typical wavelengths of 600 -1000nm. The mean power of such devices is generally low (1-100mW), though the peak power may be much higher than this. These devices most commonly fall into the category of Class 3B Lasers, though some (typically those available on the internet) might be lower powered (Class 2), whilst recently there have been a number of Class 4 lasers which are being promoted (higher power devices) though a definitive benefit from using a higher power device has yet to be established (other than shorter treatment times). A useful description of Laser Classes can be found at www.lasersafetyfacts.com/laserclasses.html. The classification is based on the potential ‘risk’ of the laser energy to the eye.

Laser Classes based on risk to the eye (from www.lasersafetyfacts.com)

The treatment device may be a single emitter or a cluster of several emitters, though it is common for most emitters in a cluster to be non laser type devices. The beam from single probes is usually narrow (Æ1mm-6 or 7mm) at the source. A cluster probe will usually incorporate both higher and lower power emitters of different wavelengths, typically incorporating visible red and infrared devices.

Examples of LILT Probes

The output may be continuous or pulsed, with narrow pulse widths (in the nano or micro second ranges) and a wide variety of pulse repetition rates from 2Hz up to several thousand Hz. It is difficult to identify the evidence for the use of pulsing from the research literature, though it would appear to be a general trend that the lower puling rates are more effective in the acute conditions whilst higher pulse rates work better in more chronic conditions. There is a growing body of support that suggests that the pulsing settings are of secondary importance in terms of clinical doses.

 
Light Absorption in the Tissues:

 

As with any form of energy used in electrotherapy, the energy must be absorbed by the tissues in order to have some effect. If exactly the same amount of energy left the tissues which was introduced into them, it is difficult to rationalise what kind of effect might have been achieved. The absorption of light energy within the tissues is a complex issue, but generally, the shorter wavelengths (ultraviolet & shorter visible) are primarily absorbed in the epidermis by the pigments, amino & nucleic acids. The longer IRR wavelengths (>1300nm) appear to be rapidly absorbed by water & therefore have a limited penetration into the tissues. The band between (i.e. 600-1000nm) are capable of penetration beyond the very superficial epidermis & are, in part at least, available for absorption by other biological tissues.

 

LLLT when applied to the body tissues, delivers energy at a level sufficient to disturb local electron orbits & result in the generation of heat, initiate chemical change, disrupt molecular bonds & produce free radicals. These are considered to be the primary mechanisms by which LLLT achieves its physiological & therefore therapeutic effects and the primary target is effectively the cell membrane (see below).

 

Although much of the applied laser light is absorbed in the superficial tissues, it is proposed that deeper or more distant effects can be achieved, possibly as a secondary consequence via some chemical mediator or second messenger systems. Whilst this is an attractive explanation, there is limited evidence to fully support this contention.

 

The actual penetration of LLLT at common wavelengths is a widely debated point & it is common to find widely varying values cited in the literature. It is often claimed that because laser light is monochromatic, polarised & coherent it is capable of greater penetration than 'normal' (or non-coherent) light. This should give penetration depths of 3-7mm for visible red light & some 30-40mm for IRR laser light though 10-15mm is probably a more realistic penetration in human tissue. Enwemeka (2001) provides an example of a study which suggests that the depth of penetration of laser light (tested at 2 different wavelengths) is NOT related to the applied power and that stronger laser does NOT penetrate further into the tissues.

 

The fact that the polarisation appears to be lost in the tissues, as is much, if not all of the coherence, will result in a shallower penetration. King cites a more realistic penetration depth for 630nm light to be 1-2mm, whilst at 800-900nm one could expect penetration depths of 2-4mm. (Penetration depth in this context refers to the depth of the tissues to which 37% of the light at the surface is able to penetrate). A very small % of the light energy available at the surface will be available at 10mm or more into the tissues.

 
Laser - Tissue Interaction:

 

As with many other forms of energy delivered to the patient under the umbrella of electrotherapy, the primary effects are divided into thermal and non thermal. LLLT is generally considered to be a non thermal energy application, though one must be careful to appreciate that delivery and absorption of any energy to the body will result in the development of heat to some extent. Non thermal in this context really relates to the non accumulative nature of the thermal energy. De Freitas + Hamblin (2016) provide a recent review of the proposed mechanisms by which laser energy (LLLT) achieves its tissue related effects whilst Prindeze et al (2012) provide a slightly older, but none the less useful paper on the same topic..

 

Photobioactivation is a commonly used phrase in connection with LILT - meaning the stimulation of various biological events using light energy but without significant temperature changes. Much, if not all the cited work on therapeutic laser consider these photobioactivation effects. Some authors have proposed that there are other terms which are preferable to photobioactivation including photobiostimulation and photobiomodulation. It provides for a great semantic argument, but assume at this point that therms are generally interchangeable.

 

Many of the early ideas of photobioactivation were proposed by Karu who reported & demonstrated several key factors. She notes in her 1987 paper that some biomolecules (DNA, RNA) change their activity in response to irradiation with low intensity visible light, but that these molecules do not appear to absorb the light directly. The cell membrane appears to be the primary absorber of the energy which then generates intracellular effects by means of a second messenger / cascade type response. The magnitude of the photoresponse was deemed to be determined at least in part by the state of the cells/tissues prior to irradiation, summarised in a simple statement that 'starving cells are more photosensitive than well fed ones'. The laser light irradiation of the tissues is seen then as a trigger for the alteration of cell metabolic processes, via a process of photosignal transduction. The often cited Arndt-Schults Law supports this proposal.

 

The list of cellular & more general physiological effects is extensive, but it must be considered realistically in that much of the work relates to in vitro experimentation with no direct proof that the results are directly related to living mammalian tissues in vivo.

The following list of physiological & cellular level effects is compiled from several reviews & research papers & does not claim to be complete or guaranteed for the in vivo situation. It does however illustrate the range & scope of photobioactivation effects.

               

  •      Altered cell proliferation

  •      Altered cell motility

  •      Activation of phagocytes

  •      Stimulation of immune responses

  •      Increased cellular metabolism

  •      Stimulation of macrophages

  •      Stimulation of mast cell degranulation

  •      Activation & proliferation of fibroblasts

  •      Alteration of cell membrane potentials

  •      Stimulation of angiogenesis

  •      Alteration of action potentials

  •      Altered prostaglandin production

  •      Altered endogenous opoid production

 
Dose Calculations:

 

Most research groups and many manufacturers, recommend that the dose delivered to a patient during a treatment session should be based on the ENERGY DENSITY rather than the power or other measure of dose. Energy Density is measured in units of Joules per square centimetre (J/cm2). One of the most significant inhibitors to the more widespread adoption of laser therapy in the clinical environment relates to the difficulty in getting these ‘effective’ laser doses to work on a particular machine. Few devices enable the practitioner to set the dose in J/cm2. Some will provide Joules, some Watts, some Watts/cm-2 etc etc. It is currently argued that Joules (i.e. Energy) may in fact be the most critical parameter rather than Energy Density. The debate is not yet resolved, and the energy density will be used here, mainly because the published research almost exclusively cites it, and therefore, it may be of more use when it comes to trying to replicate an evidence based treatment dose.

 

Some machines offer 'on board' calculations of this dose, whilst other machines require the operator to make some simple calculations based on several considerations:

 

  • output power (Watts)

  • irradiation area (cm2)

  • time (seconds)

  • If PULSED - pulse width, frequency and power settings

 

ENERGY DENSITY (J/cm2) = Total amount of energy (J) / Irradiation area (cm2)

TOTAL ENERGY (J) = Average Power (Watts) x Time (sec)

AVERAGE POWER (Watts) = Peak power (W) x Frequency (Hz) x Pulse Duration (sec)

(PULSED OUTPUT ONLY)                                                              

 

There are various alternative methods for calculating these doses, but those cited above offer a reasonably simple method should one be needed.

 

Most authorities suggest that the ENERGY DENSITY per TREATMENT SESSION should generally fall in the range of 0.1 - 12.0 J/cm2 though there are some recommendations which go up to 30 J/cm2. It has been previously suggested that a maximal (single treatment) dose of 4 J/cm2 should not be exceeded. The evidence would not support that contention. Again as a generality, lower doses should be applied to the more acute lesions which would appear to be more energy sensitive.

 
Clinical Applications:

 

The recent research, both laboratory based & clinical trials, is found to concentrate on a few key areas. Most dominant amongst these are wound healing, inflammatory arthropathies, soft tissue injury and the relief of pain. There is supportive research for the clinical use of LLLT in these and other circumstances, but, as with many treatment modalities, the evidence remains somewhat controversial at the present time.

 

There are thousands of research papers on laser, and even the review papers exceed 1200, so it is all but impossible to list all applications and all research evidence in this summary. Some of the key applications are identified below

 

Open Wounds

 

There is a growing body of evidence in this context, with some mixed results, but on the whole, they are positive outcome trials. There`are useful chapters/sections in the Baxter text and more recently in the Tuner and Hode book. A general summary\might conclude that a treatment programme could be thus :

Treat to the floor of the ulcer / pressure sore / wound

Often use cluster probe to cover the area

Typically up to 2 J/cm2

Also treat margin/periphery

Often use single probe

Typically up to 4 J/cm2

 

Machado et al (2017) provide a recent systematic review which evaluates the effects of laser in pressure ulcers, though they only included 4 papers out of the 386 identified papers on the topic! Tchanque-Fossuo, C. et al. (2016) review the use of laser in diabetic foot ulcer treatment. Kuffler (2016) provides a broad review of the use of laser in wound healing.

 

Inflammatory Arthropathies

There have been several trials involving the use of LILT and various inflammatory problems in joints. As with the wound work, there are mixed results, but the general trend appears to be largely supportive. The recent Ottawa Panel review was supportive of laser therapy in RA. Shukla + Muthusekhar (2016) provide a supportive systematic review for the use of laser in TMJ/TMD related disorders. Other joint related papers which might be useful include: Baltzer et al (2016); Huang et al (2015); Ip (2015); Meireles et al (2011); Youssef et al (2016);

 

Soft Tissue Injury

There is a fairly widespread use of LILT in a variety of soft tissue treatments. Some results are excellent and others poor. It is possible that the weak results relate to incorrect doses or possibly considering the use of laser therapy for injuries that are simply beyond the reach of the energy delivered (see penetration section above). The Tuner and Hode book has multiple examples of effective (and less effective) soft tissue treatments with LILT and identifies some of the key research in this area. Alves et al (2014) provide a useful review of the effects of laser therapy in skeletal muscle repair.

 

Pain

It was broadly assumed (until more recently) that the effect of laser therapy with regards to pain relief was primarily a secondary effect of dealing with the inflammatory state. Whilst this may well be true (to some extent at least), there is growing evidence that laser therapy can have a more direct effect of nerve conduction characteristics and hence may result in reduced pain as a more direct effect of the therapy. A recent example of a paper along these lines would be Vinck et al 2005. Holanda et al (2017) provide a potential explanation for the role of laser therapy in relation to neuropathic pain. Li et al (2016) provide a review + meta analysis for the use of laser in Carpal Tunnel syndromes, supporting its application

 

DOMS, Exercise and Post Exercise Recovery

 

Another rapidly developing growth area in the laser related research considers the use of this modality as a treatment option in DOMS (delayed onset muscle soreness) and its use before or after exercise as a means to enhance performance or reduce recovery time. An example of a paper of this style (laser pre exercise) would be Pinto et al (2016). Useful reviews can be found in : Leal-Junior et al. (2015), Nampo et al. (2016a, b);

 

Oral and Dental Interventions

There has been a rapidly expanding body of literature relating to (a) dental/maxillary and (b) oral mucositis applications for laser therapy. Whilst these are beyond common current laser therapy usage, it is highly likely they will become more normal and thus more common in the near future, especially given the strength of the evidence. Key recent papers would include Santinoni et al (2017), Mercadante et al (2017), Robijns et al (2016), Pandeshwar et al 2016

 

Laser Acupuncture

Again, this is somewhat beyond the main content of this brief overview, but laser (most commonly with a single diode or ‘pen’ applicator) has been used at or over acupuncture points with good results. TENS and other therapies are also applied in this way, so it is not ‘unique’ to laser. Examples of papers which have successfully employed this (laser) technique include : Al Rashoud et al (2014); Law et al (2015) [systematic review]; Round et al (2013); Steurer (2015); Tseng et al (2016)

 
REFERENCES:

 

In addition to the references cited in the text above, there is an updated chapter in the Electro textbook (2020) by Baxter and Nussbaum which provides a comprehansive review of the current state of the art:

Electrophysical Agents: Evidence Based Practice, Watson & Nussbaum, (2020) Elsevier.

Baxter, D. and Nussbaum, E. Laser/Photobiomodulation (Chapter 10)

Al Rashoud, A. et al. (2014). "Efficacy of low-level laser therapy applied at acupuncture points in knee osteoarthritis: a randomised double-blind comparative trial." Physiotherapy 100(3): 242-248.

 

Alves, A. et al. (2014). "Effects of low-level laser therapy on skeletal muscle repair: a systematic review." Am J Phys Med Rehabil 93(12): 1073-1085.

 

Baltzer, A. et al. (2016). "Positive effects of low level laser therapy (LLLT) on Bouchard's and Heberden's osteoarthritis." Lasers Surg Med 48(5): 498-504.

 

Baxter, D (1993) Therapeutic Lasers, Pub : Churchill Livingstone

 

Baxter, D. (2008) Low Intensity Laser Therapy. Chapter 11 in : Electrotherapy : Evidence Based Practice. Editor : T Watson. Elsevier.

 

de Abreu Chaves, M. et al. (2014). "Laser and LED–Comparison of Effects." An Bras Dermatol 89(4): 616-623.

 

De Castro, I et al. (2014). "Do laser and led phototherapies influence mast cells and myofibroblasts to produce collagen?" Lasers Med Sci 29(4): 1405-1410.

 

de Freitas, L. and Hamblin, M. (2016). "Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy." IEEE J Sel Top Quantum Electron 22(3).

 

Enwemeka, C. (2001). "Attenuation and penetration of visible 632.8 nm and invisible infra-red 904nm light in soft tissues." Laser 13: 96.

 

Holanda, V. et al. (2017). "The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light." Lasers in surgery and medicine: (ahead of print : DOI 10.1002/lsm.22628

 

Huang, Z., et al. (2015). "Effectiveness of low-level laser therapy in patients with knee osteoarthritis: a systematic review and meta-analysis." Osteoarthritis Cartilage 23(9): 1437-1444.

 

Ip, D. (2015). "Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?" Lasers Med Sci 30(9): 2335-2339.

 

Kitchen,S Partridge,C. (1991) A Review of Low Level Laser Therapy. Physiotherapy 77(161-168)

 

King,P. (1990)  Low-level laser therapy: A Review. Physiotherapy Theory & Practice 6(127-138)

 

Karu,T. (1987) Photobiological fundamentals of low power laser therapy IEEE Journal of Quantum Electronics QE23(10);1703-1717

 

Kuffler, D. (2016). "Photobiomodulation in promoting wound healing: a review." Regen Med 11(1): 107-122.

 

Law, D., et al. (2015). "Laser acupuncture for treating musculoskeletal pain: a systematic review with meta-analysis." J Acupunct Meridian Stud 8(1): 2-16.

 

Leal-Junior, E. et al. (2015). "Effect of phototherapy (low-level laser therapy and light-emitting diode therapy) on exercise performance and markers of exercise recovery: a systematic review with meta-analysis." Lasers Med Sci 30(2): 925-939.

 

Li, Z. J., et al. (2016). "Effectiveness of low-level laser on carpal tunnel syndrome: A meta-analysis of previously reported randomized trials." Medicine (Baltimore) 95(31): e4424.

 

Lima, A. et al. (2017). "Photobiomodulation (Laser and LED) on Sternotomy Healing in Hyperglycemic and Normoglycemic Patients Who Underwent Coronary Bypass Surgery with Internal Mammary Artery Grafts: A Randomized, Double-Blind Study with Follow-Up." Photomed Laser Surg 35(1): 24-31.

 

Machado, R. et al. (2017). "Low-level laser therapy in the treatment of pressure ulcers: systematic review." Lasers Med Sci. DOI : 10.1007/s10103-017-2150-9

 

Meireles, S. et al. (2011). "Low-level laser therapy on hands of patients with rheumatoid arthritis." Clin Rheumatol 30(1): 147-148.

 

Mercadante, V., et al. (2017). "Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis." Oral Oncol 66: 64-74.

 

Nampo, F. et al. (2016a). "Effect of low-level phototherapy on delayed onset muscle soreness: a systematic review and meta-analysis." Lasers Med Sci 31(1): 165-177.

 

Nampo, F. et al. (2016b). "Low-level phototherapy to improve exercise capacity and muscle performance: a systematic review and meta-analysis." Lasers Med Sci 31(9): 1957-1970.

 

Ohshiro,T. Calderhead,R. (1988) Low Level Laser Therapy

                Pub.John Wiley & Sons

 

Ottawa Panel (2004). "Ottawa panel evidence-based clinical practice guidelines for electrotherapy and thermotherapy interventions in the management of rheumatoid arthritis in adults."  84(11): 1016-1043.

 

Pandeshwar, P., et al. (2016). "Photobiomodulation in oral medicine: a review." J Investig Clin Dent 7(2): 114-126.

 

Pinto, H. et al. (2016). "Photobiomodulation Therapy Improves Performance and Accelerates Recovery of High-Level Rugby Players in Field Test: A Randomized, Crossover, Double-Blind, Placebo-Controlled Clinical Study." J Strength Cond Res 30(12): 3329-3338.

 

Prindeze, N. et al. (2012). "Mechanisms of action for light therapy: a review of molecular interactions." Exp Biol Med (Maywood) 237(11): 1241-1248.

 

Robijns, J., et al. (2016). "The use of low-level light therapy in supportive care for patients with breast cancer: review of the literature." Lasers Med Sci. DOI - 10.1007/s10103-016-2056-y

 

Round, R., et al. (2013). "Auricular acupuncture with laser." Evid Based Complement Alternat Med 2013: 984763.

 

Santinoni, C. et al. (2017). "Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review." J Photochem Photobiol B 169: 83-89.

 

Shukla, D. and M. R. Muthusekhar (2016). "Efficacy of low-level laser therapy in temporomandibular disorders: A systematic review." Natl J Maxillofac Surg 7(1): 62-66.

 

Steurer, J. (2015). "[Acupuncture with needles or lasers without clinically relevant effect on knee osteoarthritis]." Praxis (Bern 1994) 104(1): 51-52.

 

Tchanque-Fossuo, C. et al. (2016). "A systematic review of low-level light therapy for treatment of diabetic foot ulcer." Wound Repair Regen 24(2): 418-426.

 

Tseng, C. et al. (2016). "Effect of Laser Acupuncture on Anthropometric Measurements and Appetite Sensations in Obese Subjects." Evid Based Complement Alternat Med 2016: 9365326.

 

Tuner, J. and L. Hode (2002). Laser Therapy: Clinical Practice & Scientific Background. Grangesberg, Sweden, Prima Books AB.

 

Tuner, J. and L. Hode (2004). The Laser Therapy Handbook. Prima Books AB

 

Vinck, E. et al. (2005). "Evidence of changes in sural nerve conduction mediated by light emitting diode irradiation." Lasers Med Sci 20(1): 35-40.

 

Youssef, E. et al. (2016). "Effect of Laser Therapy on Chronic Osteoarthritis of the Knee in Older Subjects." J Lasers Med Sci 7(2): 112-119.