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Mechanism of Phototherapy
 

Background

Phototherapy, is a treatment modality in which light of very specific wavelengths (between 620 nm – 880 nm) and power output is directed onto compromised tissue in order to produce a biological reaction within the cell.  The result of the biological reaction, called the photo-biological response, leads in turn to a cascade of events optimising and accelerating healing.

The use of phototherapy in stimulating and regulating cell growth is not a new concept.  NASA has been working on the use of LED–based phototherapy units for use in wound healing for more than a decade.  Their research came about due to the effects noted when light of a specific wavelength was shown to accelerate plant growth.  Due to insufficient levels of wound healing taking place in astronauts in zero-gravity conditions, they investigated the use of such phototherapy modules in wound healing.

This research has continued and the remarkable effects of phototherapy on wound healing and other conditions involving cellular damage has been the subject of numerous academic papers in peer-reviewed journals. Numerous conditions have been treated using NASA-based LED arrays and the list of treatable conditions, and the parameters necessary to treat them, is growing steadily. 

 

 

Cellular effects of Phototherapy

 

During any tissue damage - whether due to injury, wounds, inflammation or infection - cellular integrity and function are compromised.  Without a means to reverse or ameliorate such damage, such cells will eventually die (by apoptosis or necrosis) and healing will be protracted and slow, resulting in pain, tissue loss, swelling and inflammation, further crippling the patient.

Light of highly specific wavelengths, which has been optimized with Photizo™, works at the cellular level, stimulating the production of more energy (ATP: adenosine tri-phosphate) within cells. This allows cells to resume their normal functioning and make new blood vessels, nerve tissue, bone cells, and divide to form new cells. Phototherapy prevents overproduction of scar tissue by increasing and regulating collagen production and ensures quicker cellular regeneration. Research has shown that lymph vessels, venous and arterial diameters can be greatly increased (vasodilatory effect) with the use of phototherapy, increasing circulation to and from the site, thereby reducing edema, swelling and inflammation.  Improved circulation and relief from ischaemia also help the cells to take up more nutrients and oxygen as well as to dispose of waste products more effectively.  This speeds up the healing process.  Finally, phototherapy also has a pain-relieving effect by reducing the excitability of nerve tissue and increasing the secretion of endorphins.

Another major benefit of phototherapy is that it complements supplements which the patient would ordinarily have used, but which would not have been bio-available – phototherapy assists the cell in regaining function and taking up what is available in the surrounding media.  Therefore one might find that with the use of phototherapy, medicines and topical ointments reach the target areas sooner and have a greater effect than compared to using such medicines and ointment without the use of phototherapy.

 

When and where can I use LED-based Phototherapy?

Phototherapy, due to its mechanism of action, can be used in various conditions, for example:
Skin conditions: wounds, bite wounds, de-gloving wounds, lacerations, Hyaloma tick bite necrosis, hot-spots, abscesses, acral lick granuloma, bruising, skin grafts, saddle sores
Musculoskeletal: arthritis, tendonitis, myositis, sprains, bruising, fractures, back and neck pain, splints, synovitis, osteitis
Postoperative: on any wound or area treated surgically
Other:
hematoma, seroma, corneal ulcerations, viral/herpes-related conditions, sinusitis, cellulitis and any other area of inflammation

   

What is the difference between LED's (Ligh Emitting Diodes) and Lasers?

Current opinion is that laser and phototherapy machines are just convenient devices for delivering a certain wavelength and it is the wavelength that causes the effect and not the light-emitting device that is being used.   However, LED-based arrays are currently the probes of choice, due to their lower cost, on average higher output, bigger coverage (meaning shorter treatment times), less maintenance being required, and being more robust when compared to laser-based units. 

   

More scientific detail on the effects of phototherapy

If light is administered at the correct dose, certain cell functions are stimulated (photoresponse), and this is particularly evident if the cell and tissue in question have impaired function because a cell whose overall redox potential (pH and oxygen status) is shifted to a reduced state, is more sensitive to irradiation.

Think of light as a drug and therefore the need to establish which drug is best, and also the optimum dose and treatment schedule.

In order for a biological response to take place within tissue, light must firstly be absorbed.  Unless light of a particular wavelength is absorbed by a system, no photochemistry (or photophysics) will occur, and no photobiological effects will be observed, no matter how long one irradiates with that wavelength of light.  We also need the correct wavelength of light for the specific condition and/or patient and the correct dose (measured in Joules) for each condition treated.

The diverse tissue and cell types within the body all have their own unique light absorption characteristics (absorption spectra); that is, they will only absorb light at a specific wavelength and not at others because of their individual and unique structure.  For example: skin layers, because of their high blood and water content, absorb red light very readily, while calcium and phosphorus found in bone absorb light of a different wavelength.

Even with the proper wavelength and dose of radiation, phototherapy will not be effective on every system and/or situation.  The magnitude of the phototherapy effect depends on the physiological state of the cell at the moment of irradiation.  This may explain why there is often no phototherapeutic effect observed when irradiating fresh experimental wounds, while an effect is observed for "old" wounds.  Light will only stimulate cell proliferation if the cells are growing poorly at the time of the irradiation.  If a cell is fully functional, there is nothing for radiation to stimulate, and no therapeutic benefit will be observed.  An analogy would be that patients will show no beneficial effect of vitamin therapy if they already receive an adequate supply of vitamins in their daily diet.

When a photon (light) is absorbed by a molecule, the electrons of that molecule are raised to a higher energy state.  This excited molecule must lose its extra energy, and it can do this either by 1) re-emitting a photon of longer wavelength (i.e., lower energy) as fluorescence or phosphorescence, or 2) it can lose energy by giving off heat, or 3) it can lose energy by photochemistry.  Photobiological responses are the result of photochemical and/or photophysical changes produced by the absorption of light irradiation.
 
It is known today that visible and near-infrared radiation is absorbed in the respiratory chain molecules in the mitochondria called cytochrome c oxidase.  This sets in motion a chain of biological events resulting in a photo response.

Phototherapy can also affect the pore molecules in cell membranes directly, allowing the movement of calcium into the cell, setting off a cascade of events within and between cells.  The cellular calcium ion concentration can be abruptly raised for signalling purposes by transiently opening calcium channels in the plasma or intracellular membranes.  The catalytic activities of many enzymes are regulated by the calcium concentration.

Phototherapy can, by evoking a cascade of beneficial biochemical processes:
  1. Stimulate the release and synthesis of adenosine triphosphate (ATP).  ATP is the major carrier of energy in all cells. Increased levels of ATP enables the cells to resume their normal functioning and to make new blood vessels, nerve tissue, and divide to form new cells.  ATP provides the chemical energy that drives the chemical reactions of the cell as well as the process of muscle contraction.  This occurs by excitation of cytochrome oxidase C, which acts as a photoreceptor to absorb specific wavelengths of light leading to a photoresponse, donating more electrons to the electron transport chain, resulting in an increase of ATP synthesis.  In addition, light activates the redox functions of the mitochondria, changes the redox state of the cytoplasm, depolarizing the cellular membrane and raising the intracellular pH.
  2. Increase RNA and DNA synthesis.  This stimulates cellular reproduction and facilitates accelerated replacement of damaged cells.
  3. Phototherapy improves the metabolism of nitric oxide (NO), promoting increased blood capillary circulation and vascular activity.  This facilitates improved regulation of vasodilatation and leads to the formation of new capillaries.  Improved circulation provides additional oxygen and nutrients to accelerate natural tissue healing processes and assists in waste product disposal.  Improved blood circulation induces a thermal-like effect in the tissue, although there is usually no heat produced from the diodes themselves. Phototherapy, by improving circulation, ensures a reduction in swelling, bruising and inflammation.
  4. Increase lymphatic system activity.  Research has shown that the lymph vessel diameter and the flow of the lymph system can be vastly increased with the use of phototherapy.  The venous diameter and the arterial diameters can also be increased.  This means that oedema can be evacuated at a much faster rate to relieve swelling.
  5. Stimulate the production of collagen.  Collagen is the most common protein found in the body.  Collagen is the essential protein used to repair damaged tissue and to replace old tissue.  It is the substance that holds cells together and has a high degree of elasticity.  By increasing collagen production less scar tissue and proud flesh is formed at the damaged site.  Stimulate fibroblastic activity which aids in the repair process.  Fibroblasts are present in connective tissue and are capable of forming collagen fibres.
  6. Stimulate tissue granulation and connective tissue projections.
  7. Increase phagocytosis.  This is an important part of the infection fighting process.  This is the body’s natural process to scavenge dead and degenerated cells and is important to the infection control process required for optimal healing to take place.
  8. Reduce the excitability of nervous tissue thereby relieving pain.  The photons of light energy enter the body as negative ions.  This calls upon the body to send positive ions like calcium among others to go to the area being treated.  These ions assist in firing the nerves thereby relieving pain.  Patients with less pain are easier to handle, work with and treat – improving patient compliance.
  9. Increases production of endorphins and serotonin from the brain, alleviating pain and having a calming effect on the patient.
  10. Stimulates acupuncture points and an immune response.
  11. Some studies indicate that phototherapy may stimulate acetylcholine release.  Acetylcholine causes cardiac inhibition, vasodilatation, gastrointestinal peristalsis and other parasympathetic effects.
   

More about penetration

Different tissue types absorb light to different degrees and different wavelengths have different penetration patterns, thus affecting penetration depth.

Dirty and dark skin reduces penetration.  Shaving and cleaning the area to be treated ensures optimal penetration so that the correct amount of joules are delivered to the treatment site for optimal healing.

Highly vascularized tissue (areas with good blood supply) absorbs more light than less vascularized tissues. Hemoglobin in the blood is responsible for most of the absorption of light, so by pressing lightly with the light emitting device against the skin, the mechanical removal of blood greatly increases the penetration depth of the light.

   

What is Photodynamic therapy?

Photodynamic therapy (PDT) is a special form of phototherapy.  It involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases.  PDT is a developing technique which can potentially destroy unwanted tissue, whilst sparing normal tissue.  PDT has the potential of working like chemotherapy but without all the side effects.

First a drug called a photosensitiser is administered to the patient by one of several routes and it is allowed to be taken up by the target cells.  The photosensitiser alone is harmless and has no effect on either healthy or abnormal tissue.  The ideal photosensitiser should be able to concentrate in cancerous cells, relative to the surrounding healthy tissue, which helps in targeting.  After a time period (specific to the photosensitiser used), all or most of the photosensitiser should be out of all normal cells, but should remain in the unwanted tissue.  Tumours, skin, and organs of the reticuloendothelial system (including liver and spleen) retain photosensitisers for a longer period.  

The second step involves the activation of the photosensitizer in the presence of oxygen with a specific wavelength of light directed toward the target tissue. The photosensitiser becomes activated and the tissue is rapidly destroyed via necrosis and apoptosis, but only precisely where the light has been directed.  Thus, by careful application of the light beam, the technique can be targeted selectively to the anaplastic or unwanted tissue, minimizing damage to adjacent healthy structures.  Cancer selectivity in treatment occurs through a combination of selective retention of the photosensitiser and selective delivery of light, giving it a dual selectivity property.
 
Cellular damage caused by PDT is a consequence of the propagation of free oxygen radicals, superoxide and hydroxyl radicals as well as ischaemic necrosis secondary to vascular occlusion that is thought to be partially mediated by thromboxane A2 release.  The light treatment induces a photochemical, not a thermal, effect.  The necrotic reaction and associated inflammatory responses may evolve over several days.  
The potentially adverse effect is skin photosensitivity, which means that patients must stay out of bright light for some time following the administration of the drug.  The associated tissue necrosis and inflammation is also painful and should be addressed before, during and after PDT therapy.  

It has to be emphasized that PDT is still largely an experimental therapy and is currently only applicable to a very small range of patients.  More research is needed to further develop and assess PDT with different drugs in different clinical situations.  Nevertheless there is growing confidence that PDT will soon become an added weapon in the fight against cancer and other diseases.

 

 

 

© 2006 Vet - Light