Abstract
Objectives
Low level light/laser therapy (LLLT) is the direct application of light to stimulate cell responses (photobiomodulation) in order to promote tissue healing, reduce inflammation and induce analgesia. There have been significant studies demonstrating its application and efficacy at many sites within the body and for treatment of a range of musculoskeletal injuries, degenerative diseases and dysfunction, however, its use on oral tissues has, to date, been limited. The purpose of this review is to consider the potential for LLLT in dental and oral applications by providing background information on its mechanism of action and delivery parameters and by drawing parallels with its treatment use in analogous cells and tissues from other sites of the body.
Methods
A literature search on Medline was performed on laser and light treatments in a range of dental/orofacial applications from 2010 to March 2013. The search results were filtered for LLLT relevance. The clinical papers were then arranged to eight broad dental/orofacial categories and reviewed.
Results
The initial search returned 2778 results, when filtered this was reduced to 153. 41 were review papers or editorials, 65 clinical and 47 laboratory studies. Of all the publications, 130 reported a positive effect in terms of pain relief, fast healing or other improvement in symptoms or appearance and 23 reported inconclusive or negative outcomes. Direct application of light as a therapeutic intervention within the oral cavity (rather than photodynamic therapies, which utilize photosensitizing solutions) has thus far received minimal attention. Data from the limited studies that have been performed which relate to the oral cavity indicate that LLLT may be a reliable, safe and novel approach to treating a range of oral and dental disorders and in particular for those which there is an unmet clinical need.
Significance
The potential benefits of LLLT that have been demonstrated in many healthcare fields and include improved healing, reduced inflammation and pain control, which suggest considerable potential for its use in oral tissues.
1
Introduction
Low level light/laser therapy (LLLT) is the application of light (usually delivered via a low power laser or light-emitting diode; LED) to promote tissue repair, reduce inflammation or induce analgesia. LLLT has been the subject of several systematic reviews for a range of musculoskeletal pathologies with favorable outcomes reported in The Lancet , British Medical Journal , International Association for the Study of Pain and the World Health Organization . Unlike many other laser treatments LLLT is not an ablating or heating based therapy but is more analogous to photosynthesis in its mode of action. LLLT also differs from photodynamic therapy (PDT), which utilizes light indirectly to trigger photosensitive dyes to produce bactericidal molecules that kill infecting microbes that cause disease. Indeed, current data indicates that PDT appears to be a useful adjunctive tool for treating oral infections in the dental specialties of oral surgery, endodontics and periodontitis (e.g. Periowave™) . In contrast, LLLT or photobiomodulation uses the action of light and light alone to directly stimulate host cells in order to reduce inflammation, relieve pain and/or promote wound healing.
Dental applications for LLLT are not well documented in comparison with musculoskeletal applications; however, more studies are now being reported. Indeed, there is now encouraging data for LLLT application in a wide range of oral hard and soft tissues and covering a number of key dental specialties including endodontics, periodontics, orthodontics and maxillofacial surgery as described below. LLLT has also been shown to have efficacy in managing chronic pain and non-healing bone and soft tissue lesions in the maxillofacial region.
The laser or LED devices applied in LLLT typically emit in the 600–1000 nm spectrum range (red to near infrared), with typical irradiance of 5 mW/cm 2 to 5 W/cm 2 and generated by devices with as little power as 1 mW, and up to 10 W. Pulsed or sometimes continuous beams are delivered. Treatment time is typically for 30–60 s per treatment point (see Glossary of terms for an explanation of “per-point”; Table 4 ) and as little as one treatment point or a dozen or more may be treated at a given time. For acute and post-operative therapy one treatment is all that is usually required however for chronic pain and degenerative conditions as many as ten sessions may be necessary. Whilst other wavelengths outside the 650–850 nm spectrum can have similar effects they do not penetrate the tissues as well as those in the red and near-infrared range .
| Beam profiler | An instrument for measuring the beam intensity distribution |
| Laser speckle | A random fuzzy looking pattern produced by coherent laser light. Technically speaking they are a random intensity pattern produced by the mutual interference of a set of wavefronts |
| LED | Light emitting diode. A narrow spectral width (one color) semiconductor light source |
| Off-label | Use for a condition other than that for which it has been officially approved by a regulatory authority (e.g. FDA in USA, CE for Europe, Health Canada, TGA in Australia) |
| “Per point” | The region of treatment which may be a small area for a single laser beam (<1 cm 2 ) or a large area of many cm 2 for a cluster/array of incorporating many laser diodes or LEDs |
| Systematic review | A review in which research about a topic has been systematically identified, appraised and summarized |
| Tissue remodeling | The third phase of tissue repair after inflammation and cell proliferation. |
| 1/ e 2 point | Light beams do not typically have defined edges and the beam distribution is not usually uniform. To calculate power density laser physicists use the mathematical function 1/ e 2 to define the area. This is the area in which 86.5% of the power is contained |
The following review provides an overview of LLLT, the background, our current mechanistic understanding, the clinical benefits and treatment parameters.
2
History and application of LLLT
In 1967, a few years after the first working laser was invented, Dr. Endre Mester at Semmelweis Medical University in Budapest, Hungary, attempted to identify if this newly developed ‘ray of light’ could induce cancer. In his experiment, hair was shaved from the backs of two groups of mice; one as the control, the other being exposed to treatment using a low-powered ruby laser. The treatment group did not develop cancer as had been predicted, however, the hair on the treated mice grew back at a faster rate than the untreated controls. Mester (1967) subsequently described this effect as “laser biostimulation” . Forty-five years later, thousands of papers have been published with over 30 in-press every month related to LLLT and its mechanism of action, downstream physiological changes and the clinical benefits as demonstrated in both randomized clinical trials and in pooled data meta-analyzed in several systematic reviews .
To-date more than 300 randomized double blind placebo controlled clinical trials have been reported. This has resulted in publication of a number of expert consensus reports for utilizing LLLT as part of standard clinical management, including:
- •
The Lancet – systematic review of LLLT for neck pain .
- •
British Medical Journal (BMJ) – systematic review and guidelines for treating tennis elbow .
- •
International Association for the Study of Pain (IASP) – fact sheets for myofascial pain syndrome, osteoarthritis and neck pain .
- •
The World Health Organization (WHO) – task force on neck pain systematic review .
- •
British Journal of Sports Medicine (BJSM) – systematic review for frozen shoulder .
- •
American Physical Therapy Association (APTA) – systematic review and clinical practice guidelines for achilles tendinopathy .
- •
European Society for Medical Oncology (ESMO) – clinical practice guidelines for oral mucositis .
- •
Multinational Association for Supportive Cancer Care (MASCC) – clinical practice guidelines for oral mucositis .
Whilst most of the clinical evidence for LLLT has been obtained from treating musculoskeletal pain, many trials relating to oral and maxillofacial indications have also now been published ( Table 1 ).
| Oral specialty | Application | LLLT effect | Refs |
|---|---|---|---|
| Endodontics | Dentinal hypersensitivity | Reduced tactile and thermal sensitivity | |
| Pulp | Improved dentin formation in the dental pulp Promotion of HDP cell mineralization |
||
| Maxillofacial | Bisphosphonate related osteonecrosis of the jaw | Reduced pain, reduced edema, pus and fistulas, improved healing | |
| Mandibular distraction Mandibular advancement |
Improved bone trabeculation and ossification Improved bone formation in condylar region Improved osteogenesis |
||
| Temporo-mandibular joint disorder | Reduced pain Improved range of mandibular movement |
||
| Trauma to the mandibular | Improved bone healing | ||
| Oral pathology | Burning mouth syndrome | Reduced symptoms, reduced pain | |
| HSV | Improved healing and reduced reoccurrence | ||
| Lichen planus | Reduced lesion size, less pain As effective as corticosteroids |
||
| Oral mucositis | Reduced incidence, duration and severity | ||
| Xerostomia/dryness | Regeneration of salivary duct epithelial cells Improved salivary flow, improved antimicrobial characteristics |
||
| Oral surgery | Healing | Improved healing after gingivectomy, reduced gingival Inflammation | |
| Paresthesia/alveolar nerve | Improved mechanical sensory perception | ||
| Third molar extraction | Reduced pain, reduced swelling, improved trismus | ||
| Orthodontics | Orthodontic pain | Reduced pain Faster remodeling |
|
| Titanium implants | Improved healing Improved attachment Improved osseointegration |
||
| Tooth movement | Accelerated tooth movement Improved osteoblast/osteoclast activity Improved collagen deposition |
||
| Pediatric | Cavity preparation Mandibular distraction Gingivitis |
Reduced pain Faster healing |
|
| Periodontics | Chronic gingivitis | Reduced inflammation Improved healing |
|
| Periodontal ligament | Increased early hyalinization | ||
| Periodontitis | Improved pocket depth Less inflammation |
||
| Prosthodontics | Denture stomatitis | Reduced yeast colonies Reduced palatal inflammation |
|
| Implants | Faster bone formation Improved bone–implant interface strength Improved osseointegration |
||
Apart from an enhanced rate of postoperative healing and better tissue remodeling, LLLT is also a major benefit for patients who are in pain, are needle phobic or cannot tolerate non-steroidal inflammatory drugs (NSAIDs) .
2
History and application of LLLT
In 1967, a few years after the first working laser was invented, Dr. Endre Mester at Semmelweis Medical University in Budapest, Hungary, attempted to identify if this newly developed ‘ray of light’ could induce cancer. In his experiment, hair was shaved from the backs of two groups of mice; one as the control, the other being exposed to treatment using a low-powered ruby laser. The treatment group did not develop cancer as had been predicted, however, the hair on the treated mice grew back at a faster rate than the untreated controls. Mester (1967) subsequently described this effect as “laser biostimulation” . Forty-five years later, thousands of papers have been published with over 30 in-press every month related to LLLT and its mechanism of action, downstream physiological changes and the clinical benefits as demonstrated in both randomized clinical trials and in pooled data meta-analyzed in several systematic reviews .
To-date more than 300 randomized double blind placebo controlled clinical trials have been reported. This has resulted in publication of a number of expert consensus reports for utilizing LLLT as part of standard clinical management, including:
- •
The Lancet – systematic review of LLLT for neck pain .
- •
British Medical Journal (BMJ) – systematic review and guidelines for treating tennis elbow .
- •
International Association for the Study of Pain (IASP) – fact sheets for myofascial pain syndrome, osteoarthritis and neck pain .
- •
The World Health Organization (WHO) – task force on neck pain systematic review .
- •
British Journal of Sports Medicine (BJSM) – systematic review for frozen shoulder .
- •
American Physical Therapy Association (APTA) – systematic review and clinical practice guidelines for achilles tendinopathy .
- •
European Society for Medical Oncology (ESMO) – clinical practice guidelines for oral mucositis .
- •
Multinational Association for Supportive Cancer Care (MASCC) – clinical practice guidelines for oral mucositis .
Whilst most of the clinical evidence for LLLT has been obtained from treating musculoskeletal pain, many trials relating to oral and maxillofacial indications have also now been published ( Table 1 ).
| Oral specialty | Application | LLLT effect | Refs |
|---|---|---|---|
| Endodontics | Dentinal hypersensitivity | Reduced tactile and thermal sensitivity | |
| Pulp | Improved dentin formation in the dental pulp Promotion of HDP cell mineralization |
||
| Maxillofacial | Bisphosphonate related osteonecrosis of the jaw | Reduced pain, reduced edema, pus and fistulas, improved healing | |
| Mandibular distraction Mandibular advancement |
Improved bone trabeculation and ossification Improved bone formation in condylar region Improved osteogenesis |
||
| Temporo-mandibular joint disorder | Reduced pain Improved range of mandibular movement |
||
| Trauma to the mandibular | Improved bone healing | ||
| Oral pathology | Burning mouth syndrome | Reduced symptoms, reduced pain | |
| HSV | Improved healing and reduced reoccurrence | ||
| Lichen planus | Reduced lesion size, less pain As effective as corticosteroids |
||
| Oral mucositis | Reduced incidence, duration and severity | ||
| Xerostomia/dryness | Regeneration of salivary duct epithelial cells Improved salivary flow, improved antimicrobial characteristics |
||
| Oral surgery | Healing | Improved healing after gingivectomy, reduced gingival Inflammation | |
| Paresthesia/alveolar nerve | Improved mechanical sensory perception | ||
| Third molar extraction | Reduced pain, reduced swelling, improved trismus | ||
| Orthodontics | Orthodontic pain | Reduced pain Faster remodeling |
|
| Titanium implants | Improved healing Improved attachment Improved osseointegration |
||
| Tooth movement | Accelerated tooth movement Improved osteoblast/osteoclast activity Improved collagen deposition |
||
| Pediatric | Cavity preparation Mandibular distraction Gingivitis |
Reduced pain Faster healing |
|
| Periodontics | Chronic gingivitis | Reduced inflammation Improved healing |
|
| Periodontal ligament | Increased early hyalinization | ||
| Periodontitis | Improved pocket depth Less inflammation |
||
| Prosthodontics | Denture stomatitis | Reduced yeast colonies Reduced palatal inflammation |
|
| Implants | Faster bone formation Improved bone–implant interface strength Improved osseointegration |
||
Apart from an enhanced rate of postoperative healing and better tissue remodeling, LLLT is also a major benefit for patients who are in pain, are needle phobic or cannot tolerate non-steroidal inflammatory drugs (NSAIDs) .
3
Mechanism of action of LLLT
Most of the effects of LLLT can be explained by light absorption within the mitochondria ( Fig. 1 ). Cells can contain up to several thousand mitochondria, which generate cellular energy (ATP) from oxygen and pyruvate. In addition, in stressed or ischemic tissues, mitochondria synthesize nitric oxide (mtNO) , which competes and can displace oxygen from binding to Cytochrome c oxidase (CcO) (the terminal enzyme in the electron transport chain necessary for energy generation) . Two negative effects result: reduced ATP synthesis and increased oxidative stress (leading to inflammation via activation of the inflammatory “master switch” transcription factor, NF-κB) .
3.1
The consequences of LLLT on hypoxic/stressed cells
3.1.1
Primary effect: absorption by cytochrome c oxidase
CcO absorbs red and near-infrared light, the transfer of light energy by this enzyme triggers a series of downstream effects ( Fig. 1 ).
3.1.2
Secondary effect: modulation of ATP, nitric oxide and reactive oxygen species
Changes in ATP, reactive oxygen species and nitric oxide occur due to light absorption by CcO, which are redox state and dose dependent. In hypoxic or otherwise stressed cells it has been shown that following LLLT, nitric oxide is released from CcO, ATP synthesis is increased and oxidative stress is reduced .
3.1.3
Tertiary effect: downstream intracellular responses (gene transcription, and cellular signaling)
There are many downstream effects of LLLT including nitric oxide release, increased ATP synthesis and reduced oxidative stress. These effects are context and cell type dependent. Either directly or indirectly these biochemical intermediates affect components in the cytosol, the cell membrane, and nuclear functions that control gene transcription and subsequently regulate cellular responses such as proliferation, migration, necrosis and inflammation .
3.1.4
Quaternary effect: extracellular, indirect, distant effects
Tissues that have not absorbed photons can also be affected indirectly via bioactive molecules released from cells that have been stimulated by absorbed light. Cells in the blood and lymph can also be activated and subsequently promote systemic effects such as autocrine, paracrine, and endocrine and termed as “bystander” effects.
3.2
Edema/lymphatic flow
There is good evidence that LLLT also improves lymphatic flow. A systematic review of eight clinical trials of LLLT for post-mastectomy lymphoedema concludes that “There is moderate to strong evidence for the effectiveness of LLLT for the management of breast cancer related lymphoedema” . A controlled clinical trial on football players with second degree ankle sprains, found a significant reduction in edema volume in the laser group compared with the placebo . A laboratory trial on Carrageenan-induced edema in the mouse paw also found that treating lymph nodes alone was sufficient to reduce the swelling . The mechanism of action of the LLLT however was not elucidated.
3.3
Analgesia
Analgesic effects are probably a result of a different biological mechanism from those of the increased ATP/reduced oxidative stress model described above. According to a systematic review of laser analgesia mechanisms by Chow et al. , laser light with higher irradiance (>300 mW/cm 2 ), when absorbed by nociceptors, exert an inhibitory effect on Aδ and C pain fibers, which slows conduction velocity, reduces amplitude of compound action potentials and suppresses neurogenic inflammation. Chow’s own laboratory studies suggest that LLLT blocks anterograde transport of ATP-rich mitochondria in dorsal root ganglion neurons. Varicosities result from the inhibitive effect, which is normally associated with disruption of microtubules and the resulting block of anterograde transport of ATP-rich mitochondria. Interruption of fast axonal flow reduces the availability of ATP necessary for microtubule polymerization, and maintenance of the resting potential . This effect is completely reversible and may last only 48 h , however, more work is needed to fully characterize the complex mechanism of action.
3.4
Myofascial trigger points
The palpable nodules in taut muscle bands and contraction of muscle fibers that lead to muscle spasms and limited joint movement are referred to as myofascial trigger points. They are a component of several pain conditions, including migraine, tension-type headaches, temporomandibular disorder and neck pain. The motor end plate is central to the etiology of the disorder and electromyography (EMG) studies have shown abnormally high electrical activity over trigger points. Electrical activity is reduced after LLLT and clinical studies have shown that LLLT has immediate and cumulative effects on reducing pain , however, the mechanism of action resulting on this effect is not yet fully elucidated.
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