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Light Therapy Research 2018-07-23T20:52:23+00:00

Photobiomodulation-Light Therapy has been shown in numerous studies to stimulate the body’s own capacity to heal. It is a newer therapy and is being researched all over the world.

RESEARCH

Listed below are just some of the research studies on the benefits of photobiomodulation-Light Therapy.

Photobiomodulation-Light Therapy for Concussions, TBI and Neurocognitive Disorders

The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging…

By:João Gustavo Rocha, Peixoto dos Santos, Wellingson Silva Paiva, Manoel Jacobsen Teixeira

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Background: Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI).

By: Connor Thunshelle and Michael R. Hamblin, PhD

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Three traumatic brain injuries (TBIs) occur every minute in the United States. TBI is a major medical problem worldwide.1 More than 5,000,000 Americans are living with TBI-related disabilities with an annual cost of $60–76.5 billion.1,2 Nonpenetrating, mild TBI (mTBI) is the most common type (75%). mTBI is defined by loss of consciousness (LOC) lasting £30 min (or no LOC), and with a period of altered mental status (amnesia/confusion) lasting up to 24 h. Persistent cognitive problems occur in 5–22% of cases.

By: Margaret A. Naeser, PhD, LAc and Michael R. Hamblin, PhD

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Alzheimer’s and Parkinson’s disease are the two most common neurodegenerative disorders. They develop after a progressive death of many neurons in the brain. Although therapies are available to treat the signs and symptoms of both diseases, the progression of neuronal death remains relentless, and it has proved difficult to slow or stop. Hence, there is a need to develop neuroprotective or disease-modifying treatments that stabilize this degeneration. Red to infrared light therapy (λ =600–1070 nm), and in particular light in the near infrared (NIr) range, is emerging as a safe and effective therapy that is capable of arresting neuronal death. Previous studies have used NIr to treat tissue stressed by hypoxia, toxic insult, genetic mutation and mitochondrial dysfunction with much success. Here we propose NIr therapy as a neuroprotective or disease-modifying treatment for Alzheimer’s and Parkinson’s patients.

By: Daniel M. Johnstone , Cécile Moro , Jonathan Stone , Alim-Louis Benabid and John Mitrofanis

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The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging. Different brain networks work together to form an important part of the cognition process, and they can be affected by TBI. The default mode network (DMN) plays an important central role in normal brain activities, presenting greater relative deactivation during more cognitively demanding tasks. After deactivation, it allows a distinct network to activate. This network (the central executive network) acts mainly during tasks involving executive functions. The salience network is another network necessary for normal executive function, and its activation leads to deactivation of the DMN. The use of red or near-infrared (NIR) light to stimulate or regenerate tissue is known as photobiomodulation. It was discovered that NIR (wavelength 800–900 nm) and red (wavelength 600 nm) light-emitting diodes (LEDs) are able to penetrate through scalp and skull and have the potential to improve the subnormal, cellular activity of compromised brain tissue. Based on this, different experimental and clinical studies were done to test LED therapy for TBI, and promising results were found. It leads us to consider developing different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients.

By: João Gustavo Rocha, Peixoto dos Santos, Wellingson Silva Paiva, and Manoel Jacobsen Teixeira

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Transcranial laser stimulation of the brain with near-infrared light is a novel form of non-invasive photobiomodulation or low-level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near-infrared spectroscopy (fNIRS).

By: Fenghua Tian, PhD; Snehal N. Hase, MS;  F. Gonzalez-Lima, PhD; and Hanli Liu, PhD

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Low-level light therapy (LLLT) with transcranial laser is a non-invasive form of neuroenhancement shown to regulate neuronal metabolism and cognition. Attention bias modification (ABM) is a cognitive intervention designed to improve depression by decreasing negative attentional bias, but to date its efficacy has been inconclusive. Adjunctive neuroenhancement to augment clinical effectiveness has shown promise, particularly for individuals who respond positively to the primary intervention.

By: Seth G. Disner, PhD; Christopher G. Beevers, PhD; and Francisco Gonzalez-Lima, PhD

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The present study examined whether the application of red and near-infrared (NIR) light, utilizing light-emitting diodes (LED) applied directly to the head could improve cognitive function, particularly executive function and verbal memory, in chronic, mTBI patients. Photons in the red and NIR wavelengths have the potential to improve subnormal, cellular activity of brain tissue that has been damaged by brain trauma.

By: Margaret A. Naeser, Ross Zafonte, Maxine H. Krengel, Paula I. Martin, Judith Frazier, Michael R. Hamblin, Jeffrey A. Knight, William P. Meehan III, and Errol H. Baker

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This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer’s disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10–24 would improve when treated with near-infrared photobiomodulation (PBM) therapy. Background: Animal studies have presented the potential of PBM for AD. Dysregulation of the brain’s default mode network (DMN) has been associated with AD, presenting the DMN as an identifiable target for PBM. Materials and methods: The study used 810 nm, 10 Hz pulsed, light-emitting diode devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN (bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus). Five patients with mild to moderately severe cognitive impairment were entered into 12 weeks of active treatment as well as a follow-up no-treatment, 4-week period. Patients were assessed with the MMSE and Alzheimer’s Disease Assessment Scale (ADAS-cog) tests. The protocol involved weekly, inclinic use of a transcranial-intranasal PBM device; and daily at-home use of an intranasal-only device. Results: There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4- week period. This is the first completed PBM case series to report significant, cognitive improvement in mild to moderately severe dementia and possible AD cases. Conclusions: Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia and AD.

By: Anita E. Saltmarche, RN, MHSc; Margaret A. Naeser, PhD; Kai Fai Ho, PhD; Michael R Hamblin, PhD; and Lew Lim, PhD, DNM, MBA

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Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer’s and Parkinson’s), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or “brain caps”. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.

By: Michael R. Hamblin

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This year marks the 50th anniversary of the discovery of the laser. The development of lasers for medical use, which became known as low-level laser therapy (LLLT) or photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly mainstream modality, especially in the areas of physical medicine and rehabilitation. At first used mainly for wound healing and pain relief, the medical applications of LLLT have broadened to include diseases such as stroke, myocardial infarction, and degenerative or traumatic brain disorders. This review will cover the mechanisms of LLLT that operate both on a cellular and a tissue level. Mitochondria are thought to be the principal photoreceptors, and increased adenosine triphosphate, reactive oxygen species, intracellular calcium, and release of nitric oxide are the initial events. Activation of transcription factors then leads to expression of many protective, anti-apoptotic, anti-oxidant, and pro-proliferation gene products. Animal studies and human clinical trials of LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury, degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be covered.

By: Javad T. Hashmi, MD; Ying-Ying Huang, MD; Bushra Z. Osmani, MD; Sulbha K. Sharma, PhD; Margaret A. Naeser, PhD, LAc; Michael R. Hamblin, PhD

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We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and welltolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

By: Paolo Cassano, Samuel R. Petrie, Michael R. Hamblin, Theodore A. Henderson, Dan V. Iosifescu

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We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/ cm2 , 25 mW/cm2 ) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6- weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis.

By: Weijun Xuan, Liyi Huang, and Michael R. Hamblin

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Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient’s left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects.

By: Fredric Schiffer, Andrea L Johnston, Caitlin Ravichandran, Ann Polcari, Martin H Teicher, Robert H Webb and Michael R Hamblin

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Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer’s disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at an age when substantial pathology is already present in the cerebral cortex.

By: Sivaraman Purushothuman, Daniel M Johnstone, Charith Nandasena, John Mitrofanis and Jonathan Stone

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Alzheimer’s disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer’s disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aβ) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer’s drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600–1000 nm) was associated with a reduction in the size and number of amyloid-β plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060–1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation’s institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement.

By: Marvin H Berman, James P Halper, Trent W Nichols, H Jarrett, Alan Lundy, and Jason H Huang

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Photobiomodulation using low-level laser therapy (LLLT) has been tested as a new technique to optimize recovery of patients with traumatic brain injury (TBI). The aim of this study is to evaluate inhibitory attentional control after 18 sessions of active LLLT and compare with the placebo group (sham LLLT). Our exploratory analysis will evaluate the efficacy of the active LLLT on verbal and visuospatial episodic memory, executive functions (working memory, verbal and visuospatial fluency, attentional processes), and anxiety and depressive symptoms compared to the sham group.

By: Guilherme da Cruz Ribeiro Poiani, Ana Luiza Zaninotto, Ana Maria Costa Carneiro, Renato Amaro Zangaro, Afonso Shiguemi Inoue Salgado, Rodolfo Borges Parreira, Almir Ferreira de Andrade, Manoel Jacobsen Teixeira and Wellingson Silva Paiva

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Transcranial photobiomodulation (PBM) also known as low level laser therapy (tLLLT) relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. The mechanism of action involves photon absorption in the mitochondria (cytochrome c oxidase), and ion channels in cells leading to activation of signaling pathways, up-regulation of transcription factors, and increased expression of protective genes. We have studied PBM for treating traumatic brain injury (TBI) in mice using a NIR laser spot delivered to the head. Mice had improved memory and learning, increased neuroprogenitor cells in the dentate gyrus and subventricular zone, increased BDNF and more synaptogenesis in the cortex. These highly beneficial effects on the brain suggest that the applications of tLLLT are much broader than at first conceived. Other groups have studied stroke (animal models and clinical trials), Alzheimer’s disease, Parkinson’s disease, depression, and cognitive enhancement in healthy subjects.

By: Madison Hennessy and Michael R Hamblin

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The purpose of this was to evaluate the neuroprotective effects of near-infrared (NIR) light using an in-vivo rodent model of traumatic brain injury (TBI), controlled cortical impact (CCI), and to characterize changes at the behavioral and biochemical levels. Background data: NIR upregulates mitochondrial function, and decreases oxidative stress. Mitochondrial oxidative stress and apoptosis are important in TBI. NIR enhanced cell viability and mitochondrial function in previous in-vitro TBI models, supporting potential NIR in-vivo benefits.

By: Brendan J. Quirk, Ph.D.; Michel Torbey, M.D.; Ellen Buchmann, B.S.; Sumit Verma, M.D.; and Harry T. Whelan, M.D.

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The treatment of depression has been hampered by low efficacy of antidepressant medications and safety concerns with alternative modalities. Recent work demonstrated that multi-Watt transcranial near-infrared light therapy (NILT) can effectively treat traumatic brain injury (TBI). The current objective is to explore multi-Watt NILT efficacy in a proof-of-concept study as a treatment for depression.

By: Theodore A. Henderson1, and Larry D. Morries

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Photobiomodulation (PBM) also known as low-level level laser therapy is the use of red and nearinfrared light to stimulate healing, relieve pain, and reduce inflammation. The primary chromophores have been identified as cytochrome c oxidase in mitochondria, and calcium ion channels (possibly mediated by light absorption by opsins). Secondary effects of photon absorption include increases in ATP, a brief burst of reactive oxygen species, an increase in nitric oxide, and modulation of calcium levels. Tertiary effects include activation of a wide range of transcription factors leading to improved cell survival, increased proliferation and migration, and new protein synthesis. There is a pronounced biphasic dose response whereby low levels of light have stimulating effects, while high levels of light have inhibitory effects. It has been found that PBM can produce ROS in normal cells, but when used in oxidatively stressed cells or in animal models of disease, ROS levels are lowered. PBM is able to up-regulate anti-oxidant defenses and reduce oxidative stress. It was shown that PBM can activate NF-kB in normal quiescent cells, however in activated inflammatory cells, inflammatory markers were decreased. One of the most reproducible effects of PBM is an overall reduction in inflammation, which is particularly important for disorders of the joints, traumatic injuries, lung disorders, and in the brain. PBM has been shown to reduce markers of M1 phenotype in activated macrophages. Many reports have shown reductions in reactive nitrogen species and prostaglandins in various animal models. PBM can reduce inflammation in the brain, abdominal fat, wounds, lungs, spinal cord

By: Michael R. Hamblin

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Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.

By: Julio C Rojas, F Gonzalez-Lima

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Secondary injury in the spinal cord, which results in axonal degeneration, scar and cavity formation and cell death, occurs around the site of the initial trauma and is a primary cause for the lack of axonal regeneration observed after spinal cord injury (SCI). The immune response after SCI is under investigation as a potential mediator of secondary injury. Treatment of SCI with 810 nm light suppresses the immune response and improves axonal regeneration.

By: K.R. Byrnes, R.W. Waynant, I.K. Ilev, B. Johnson, Pollard H., Srivastava M., Eidelman O., Huang, W., J.J. Anders

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Purpose: 1) To study the effectiveness of low-level laser stimulation of acupuncture points to treat paralysis in stroke patients; 2) To examine the relationship between neuroanatomical lesion sites on CT scan and potential for improvement following laser acupuncture treatments. We have conducted previous research with needle stimulation of acupuncture points in the treatment of paralysis in stroke patients (1-3).

By: Margaret Naeser, Ph.D., Lic.Ac., Dipl.Ac. (NCCAOM)

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Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800–900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients.

By: João Gustavo Rocha Peixoto dos Santos, Ana Luiza Costa Zaninotto, Renato Amaro Zângaro, Ana Maria Costa Carneiro, Iuri Santana Neville, Almir Ferreira de Andrade, Manoel Jacobsen Teixeira and Wellingson Silva Paiva

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The subject of this case study is a 29-year-old woman who suffered a brainstem stroke. She remained severely dizzy, had a non-functional left hand secondary to weakness, severe spasticity in the right hand, a right lateral sixth nerve palsy and was unable to ambulate on presentation. The stroke occurred 2 years before presentation. The subject had been treated for 21 months at two different stroke rehabilitation centres before presentation. Our stroke protocol includes photobiomodulation administered with the XR3T-1 device and ‘muscle/bone/joint/soft tissue’ recovery techniques. The patient was seen once a week for 8 weeks and treatment sessions lasted approximately 60 min. The results were dramatic: after 8 weeks of implementation of our protocol, the patient demonstrated positive change in every area of her deficits as determined by improvements in physical examination findings. The gains achieved at 8 weeks have been maintained to this day and she continues to be treated once every 4 weeks.

By: N Ab Boonswang, Mary Chicchi, Adele Lukachek, Donna Curtiss

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Repair of peripheral nerve injuries remains a major challenge in restorative medicine. Effective therapies that can be used in conjunction with surgical nerve repair to improve nerve regeneration and functional recovery are being actively investigated. It has been demonstrated by a number of peer reviewed publications that photobiomodulation (PBM) supports nerve regeneration, reinnervation of the denervated muscle, and functional recovery after peripheral nerve injury. However, a key issue in the use of PBM as a treatment for peripheral nerve injury is the lack of parameter optimization for any given wavelength. The objective of this study was to demonstrate that for a selected wavelength effective in vitro dosing parameters could be translated to effective in vivo parameters.

By: Juanita J. Anders, PhD; Helina Moges, BS; Xingjia Wu, BS; Isaac D. Erbele, MD; 1 Stephanie L. Alberico, BS; Edward K. Saidu, BS; Jason T. Smith, PhD; and Brian A. Pryor, PhD

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Photobiomodulation-Light Therapy for Injuries & Surgeries and Chronic Conditions

Background: Low level laser therapy (LLLT) is a modality that has been used by physiotherapists for more than two decades. Clinical use has largely relied on empirical data, but new evidence suggests that LLLT can trigger specific photobiological mechanisms. Objective: To review possible therapeutic windows for LLLT in inflammatory reactions. Methods: Systematic review of LLLT in studies with cell cultures and animals where inflammation is induced. Skin wound studies were excluded unless they measured the influence of drugs on LLLT effects, or made a direct comparison of LLLT and drugs in inflammation. Results: We identified 1 review, 34 cell studies, 54 animal studies and 106 skin incision studies potentially eligible for analysis. Eleven cell studies and 27 animals studies met all our inclusion criteria, and another six animal studies met our inclusion criteria for drug comparisons and LLLT interactions. There is strong evidence of an anti-inflammatory effect from LLLT, which is consistent across all 12 tested laboratory models and phases of inflammation and wavelengths between 633 and 904 nm. The magnitude of the antiinflammatory effect is not significantly different from that of nonsteroidal anti-inflammatory drugs (NSAIDs), but it is slightly less than glucocorticoid steroids. There is moderate evidence that concomitant use of glucocorticoid steroid has a negative effect on LLLT mechanisms and should be avoided. Conclusion: Red and near infrared LLLT administered with mean laser output of 2.5–100 mW, irradiation times of 16–600 s and doses of 0.6–9.6 J reduces inflammation significantly, and is equally effective as NSAIDs in animal laboratory studies. Scattered evidence from human studies have found similar antiinflammatory effects of LLLT, suggesting that this mechanism may be responsible for many of the significant effects reported in clinical LLLT studies.

By: Jan Magnus Bjordal, Rodrigo Alvaro Brando Lopes-Martins, Jon Joensen, Vegard Vereide Iversen

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The purpose of this case report is to evaluate the effect of near infrared light therapy treatments on pain and other symptoms of diabetic peripheral neuropathy (DPN).

By: Matthew M. Diduro, DC; Noah D. Marchese, B.S., D.C.

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In the last years, phototherapy has becoming a promising tool to improve skeletal muscle recovery after exercise, however, it was not compared with other modalities commonly used with this aim. In the present study we compared the short-term effects of cold water immersion therapy (CWIT) and light emitting diode therapy (LEDT) with placebo LEDT on biochemical markers related to skeletal muscle recovery after high-intensity exercise. A randomized double-blind placebo-controlled crossover trial was performed with six male young futsal athletes. They were treated with CWIT (5°C of temperature [SD ±1°]), active LEDT (69 LEDs with wavelengths 660/ 850 nm, 10/30 mW of output power, 30 s of irradiation time per point, and 41.7 J of total energy irradiated per point, total of ten points irradiated) or an identical placebo LEDT 5 min after each of three Wingate cycle tests. Pre-exercise, post-exercise, and post-treatment measurements were taken of blood lactate levels, creatine kinase (CK) activity, and Creactive protein (CRP) levels.

By: Ernesto Cesar Leal Junior, Vanessa de Godoi, José Luis Mancalossi, Rafael Paolo Rossi, Thiago De Marchi, Márcio Parente, Douglas Grosselli, Rafael Abeche Generosi, Maira Basso, Lucio Frigo, Shaiane Silva Tomazoni, Jan Magnus Bjordal, Rodrigo Álvaro Brandão Lopes-Martins

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A double-blind, placebo-controlled study using male subjects (n = 60), was conducted to investigate the efficacy of three different frequencies of combined phototherapy/low-intensity laser therapy (CLILT) in alleviating the signs and symptoms of delayed-onset muscle soreness (DOMS).

By: Craig JA, Barlas P, Baxter GD, Walsh DM, Allen JM.

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Recently, researchers have shown that phototherapy administered to skeletal muscle immediately before resistance exercise can enhance contractile function, prevent exercise-induced cell damage, and improve postexercise recovery of strength and function.

By: Paul A. Borsa, PhD, ATC, FACSM; Kelly A. Larkin, PhD, CAT(C); Jerry M. True, DC, FIACN

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We evaluated the effect on mice skeletal muscle regeneration of different doses (2.6, 8.4, and 25 J/cm2) of HeNe laser (lambda 632.8 nm; power, 2.6 mW; spot size, 0.007 cm2) applied directly to intact skin of injured muscle. Muscle injury was induced in both right and left Tibialis anterior (TA) muscles by ACL myotoxin (5 mg/kg). Right TA muscles were irradiated daily for 5 days while contralateral muscles received a sham treatment. Only the 2.6 J/cm2 dose resulted in changes such as increased mitochondrial density and muscle fibre in the TA muscles as compared to sham groups (3280 +/- 704 microns 2 versus 2110 +/- 657 microns 2, p = 0.02). We concluded that the HeNe effect on mouse muscle regeneration is dosespecific: only 2.6 J/cm2 increased muscle fibre area and mitochondrial density.

By: Amaral AC, Parizotto NA, Salvini TF

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To investigate if development of skeletal muscle fatigue during repeated voluntary biceps contractions could be attenuated by low-level laser therapy (LLLT).

By: Leal Junior EC, Lopes-Martins RA, Dalan F, Ferrari M, Sbabo FM, Generosi RA, Baroni BM, Penna SC, Iversen VV, Bjordal JM

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There are some indications that low-level laser therapy (LLLT) may delay the development of skeletal muscle fatigue during high-intensity exercise. There have also been claims that LED cluster probes may be effective for this application however there are differences between LED and laser sources like spot size, spectral width, power output, etc. In this study we wanted to test if light emitting diode therapy (LEDT) can alter muscle performance, fatigue development and biochemical markers for skeletal muscle recovery in an experimental model of biceps humeri muscle contractions.

By: Leal Junior EC, Lopes-Martins RA, Rossi RP, De Marchi T, Baroni BM, de Godoi V, Marcos RL, Ramos L, Bjordal JM

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Low level laser therapy (LLLT) also known as photobiomodulation, is a treatment that uses low-level lasers or light-emitting diodes (LEDs) to change cellular function and is a clinically well accepted tool in regenerative medicine and dentistry. Considering the variety of laser, exposure, cells and study types, the exact effects of low level laser therapy seems to be unclear. The aim of this study was to review the data published in the field of the effects of low level laser therapy on proliferation and differentiation of the cells contributing in bone regeneration.

By: Reza Amid , Mahdi Kadkhodazadeh, Mitra Ghazizadeh Ahsaie, Arian Hakakzadeh

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We wanted to test if pre-exercise muscle irradiation with 904 nm laser affects the development of fatigue, blood lactate levels and creatine kinase (CK) activity in a rat model with tetanic contractions. Thirty male Wistar rats were divided into five groups receiving either one of four different laser doses (0.1, 0.3, 1.0 and 3.0 J) or a notreatment control group. Laser irradiation was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions with 10 min intervals between them. Contractions were stopped when the muscle force fell to 50% of the peak value for each contraction; blood samples were taken before the first and immediately after the sixth contraction.

By: Leal Junior EC, Lopes-Martins RA, de Almeida P, Ramos L, Iversen VV, Bjordal JM

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Introduction: The purpose of this study was to investigate the effect of low-level laser therapy (LLLT) – 660 nm and 904 nm – before grip strength protocol in healthy subjects.

Methods: The study included 45 healthy volunteers with an average age of 22.7 (±1.4) years, subdivided into the following groups, control group: grip strength training associated with placebo LLLT; 660 nm group: LLLT (660 nm, 20 J/cm2 , power of 30 mW, and beam area of 0.06 cm2 , continuous, energy 1.2 J, and exposure time 40 seconds per point) before grip strength training and 904 nm group: LLLT (904 nm, 10 J/cm2 , peak power of 70 W and 0.13 cm2 beam area, with pulsed beam 9.500 Hz and 30 seconds of exposure time per point and emitted energy 1.2 J) before grip strength training. The LLLT was timed to contact 10 points located in the region of the superficial and deep flexor muscles of the fingers, with a total energy of 12.0 J per session. For the strength training protocol, the volunteer exercised their fingers with the dominant hand on a small table, elbow flexed at 90°, forearm in neutral, using a light extension handle. The Oxford protocol was performed during four weeks. The grip strength was assessed using a dynamometer (Jamar™). The data were evaluated by the analysis of variance (ANOVA) statistical method.

By: Rafael Barbosa, Alexandre Marcolino, Vitor Souza, Guilherme Bertolino, Marisa Fonseca, Rinaldo Guirro

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Recent studies have explored if phototherapy with low-level laser therapy (LLLT) or narrow-band light-emitting diode therapy (LEDT) can modulate activity-induced skeletal muscle fatigue or subsequently protect against muscle injury. We performed a systematic review with meta-analysis to investigate the effects of phototherapy applied before, during and after exercises. A literature search was performed in Pubmed/Medline database for randomized controlled trials (RCTs) published from 2000 through 2012. Trial quality was assessed with the ten-item PEDro scale. Main outcome measures were selected as: number of repetitions and time until exhaustion for muscle performance, and creatine kinase (CK) activity to evaluate risk for exercise-induced muscle damage. The literature search resulted in 16 RCTs, and three articles were excluded due to poor quality assessment scores. From 13 RCTs with acceptable methodological quality (≥6 of 10 items), 12 RCTs irradiated phototherapy before exercise, and 10 RCTs reported significant improvement for the main outcome measures related to performance…

By: Ernesto Cesar Pinto Leal-Junior, Adriane Aver Vanin, Eduardo Foschini Miranda, Paulo de Tarso Camillo de Carvalho, Simone Dal Corso, Jan Magnus Bjordal

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Recent studies have investigated whether low level laser therapy (LLLT) can optimize human muscle performance in physical exercise. This study tested the effect of LLLT on muscle performance in physical strength training in humans compared with strength training only. The study involved 36 men (20.8±2.2 years old), clinically healthy, with a beginner and/or moderate physical activity training pattern. The subjects were randomly distributed into three groups: TLG (training with LLLT), TG (training only) and CG (control). The training for TG and TLG subjects involved the leg-press exercise with a load equal to 80% of one repetition maximum (1RM) in the leg-press test over 12 consecutive weeks. The LLLT was applied to the quadriceps muscle of both lower limbs of the TLG subjects immediately after the end of each training session. Using an infrared laser device (808 nm) with six diodes of 60 mW each a total energy of 50.4 J of LLLT was administered over 140 s. Muscle strength was assessed using the 1RM leg-press test and the isokinetic dynamometer test. 

By: Ferraresi C, de Brito Oliveira T, de Oliveira Zafalon L, de Menezes Reiff RB, Baldissera V, de Andrade Perez SE, Matheucci Júnior E, Parizotto NA

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Low-level laser therapy (LLLT) has shown efficacy in muscle bioenergetic activation and its effects could influence the mechanical performance of this tissue during physical exercise. This study tested whether endurance training associated with LLLT could increase human muscle performance in isokinetic dynamometry when compared to the same training without LLLT. The primary objective was to determine the fatigue index of the knee extensor muscles (FIext) and the secondary objective was to determine the total work of the knee extensor muscles (TWext). Included in the study were 45 clinically healthy women (21?±?1.78 years old) who were randomly distributed into three groups: CG (control group), TG (training group) and TLG (training with LLLT group).

By: Brito Vieira WH, Ferraresi C, de Andrade Perez SE, Baldissera V, Parizotto NA

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STUDY DESIGN: Randomized crossover double-blinded placebo-controlled trial.

OBJECTIVE: To investigate if low-level laser therapy (LLLT) can affect biceps muscle performance, fatigue development, and biochemical markers of postexercise recovery.

BACKGROUND: Cell and animal studies have suggested that LLLT can reduce oxidative stress and inflammatory responses in muscle tissue.But it remains uncertain whether these findings can translate into humans in sport and exercise situations.

By: Leal Junior EC, Lopes-Martins RA, Frigo L, De Marchi T, Rossi RP, de Godoi V, Tomazoni SS, Silva DP, Basso M, Filho PL, de Valls Corsetti F, Iversen VV, Bjordal JM

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BACKGROUND: Eccentric exercises (EEs) are recommended for the treatment of Achilles tendinopathy, but the clinical effect from EE has a slow onset.

HYPOTHESIS: The addition of low-level laser therapy (LLLT) to EE may cause more rapid clinical improvement.

By: Stergioulas A, Stergioula M, Aarskog R, Lopes-Martins RA, Bjordal JM

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Muscle injuries are frequent in sports and workplace; more than 30% of the injuries seen in the physician’s office are related to skeletal muscle. These injuries can occur through a variety of mechanisms, including those arising through direct trauma (e.g., laceration and contusion) and those through indirect trauma (e.g., ischemia, denervation, and strain), but the general process of muscle repair is similar in most cases [1]. After injury, the muscle repair process begins and is divided into interdependent phases: degeneration/ inflammation, regeneration, fibrosis/scar formation, and remodeling [2]. In addition, muscle damage causes an immediate acute ischemic response releasing reactive oxygen species (ROS) including superoxide anion, hydroxyl radical, and hydrogen peroxide. Moreover, ROS may also be released due to the migration, accumulation, and activation of polymorphonuclear cells. These events will finally provoke oxidation of cell membrane lipids, protein oxidation, proteolysis, and DNA fragmentation. Disruption of muscle structural integrity and function will induce changes in transport capacity, energy production, and ionic balance [3].

By: Solange Almeida dos Santos, Andrey Jorge Serra, Tatiane Garcia Stancker, Maíra Cecília Brandão Simões, Marcia Ataíze dos Santos Vieira, Ernesto Cesar Leal-Junior, Marko Prokic, Andrea Vasconsuelo, Simone Silva Santos, and Paulo de Tarso Camillo de Carvalho

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Objectives: The purpose of this study was to investigate the effect of low-level laser therapy (LLLT) before and after exercise on quadriceps muscle performance, and to evaluate the changes in serum lactate and creatine kinase (CK) levels.

Methods: The study was randomized, double blind, and placebo controlled.

By: Filipe Abdalla dos Reis, PT, PhD; Baldomero Antonio Kato da Silva, PT, PhD; Erica Martinho Salvador Laraia, PT, MSc; Rhaiza Marques de Melo, PT; Patrı´cia Henrique Silva, PT; Ernesto Cesar Pinto Leal-Junior, PT, PhD; and Paulo de Tarso Camillo de Carvalho, PT, PhD

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The objective of the present work was to study the effect of helium-neon (He-Ne) and galliumarsenide (Ga-As) laser upon inflammatory biomarkers associated with oxidative stress: fibrinogen, nitric oxide (NO), L-citrulline, and superoxide dismutase (SOD). These were evaluated through histological assessment, in rats with experimental myopathy.

By: Servetto N, Cremonezzi D, Simes JC, Moya M, Soriano F, Palma JA, Campana VR

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Impulse infrared laser radiation (0.89 microm) was examined for effect on regeneration of cross-cut musculus gastrocnemius in adult rats (ten 3-min exposures, 2-3 procedures weekly for one month after the operation, modulating frequency 10 Hz, total course dose 3.6 J/cm2). Histological, morphometric and biochemical parameters of muscular regenerates as well as biochemical serum indices show enhanced regeneration of the skeletal muscle. Formation of the muscular organ ends earlier vs untreated muscles. This was accompanied with more active sclerotization of the muscular regenerate.

By: Buliakova NV, Zubkova SM, Azarova VS, Mikhalik LV, Varakina NI

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Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with varying rates of success. The objective of our study was to investigate the effect of laser therapy on cervical myofascial pain syndrome with a placebo-controlled doubleblind prospective study model. It was performed with a total of 53 patients (35 females and 18 males) with cervical myofascial pain syndrome. In group 1 (n=23), GaAs laser treatment was applied over three trigger points bilaterally and also one point in the taut bands in trapezius muscle bilaterally with a frequency of 1000 Hz for 2 min over each point once a day for 10 days during a period of 2 weeks. In group 2 (n=25), the same treatment protocol was given, but the laser instrument was switched off during applications. All patients in both groups were instructed to perform daily isometric exercises and stretching just short of pain for 2 weeks at home. Evaluations were performed just before treatment (week 0), immediately after (week 2), and 12 weeks later (week 14). Evaluation parameters included pain, algometric measurements, and cervical lateral flexion. Statistical analysis was done on data collected from three evaluation stages. The results were evaluated in 48 patients (32 females, 16 males). Week 2 and week 14 results showed significant improvement in all parameters for both groups. However, comparison of the percentage changes both immediately and 12 weeks after treatment did not show a significant difference relative to pretreatment values. In conclusion, the results of our study have not shown the superiority of GaAs laser therapy over placebo in the treatment of cervical myofascial pain syndrome, but we suggest that further studies on this topic be done using different laser types and dosages in larger patient populations.

By: Lale Altan, Umit Bingöl, Mehtap Aykac¸ Merih Yurtkuran

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The purpose of this article was to synthesize the scientific knowledge relevant to laser biostimulation of healing wounds. The literature reviewed suggests that biostimulation with lasers: 1) accelerates the inflammatory phase of wound healing by altering the levels of various prostaglandins, 2) increases ATP synthesis by enhancing electron transfer in the inner membrane of mitochondria, 3) quickens protein (collagen) synthesis by quickening DNA and RNA synthesis, 4) augments fibroplasia by a mechanism that is still being explored, and 5) enhances the ability of immune cells to combat invading pathogens. Although these findings were made in vitro and in vivo in various animal models, their clinical implications are quite clear. Laser biostimulation is potentially a useful tool in the treatment of wounds, particularly those cutaneous and subcutaneous wounds that are either complicated by infection or inherently require a prolonged period of time to heal. The precise dosage and frequency of treatment required to promote healing even in animal models remain elusive, as is experimental determination of the depth of penetration of lasers.

By: Enwemeka CS

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The purpose of the present study was to determine the effect of low level laser therapy (LLLT) treatment before knee extensor eccentric exercise on indirect markers of muscle damage. Thirty-six healthy men were randomized in LLLT group (n = 18) and placebo group (n = 18). After LLLT or placebo treatment, subjects performed 75 maximal knee extensors eccentric contractions (five sets of 15 repetitions; velocity = 60° seg(-1); range of motion = 60°). Muscle soreness (visual analogue scale–VAS), lactate dehydrogenase (LDH) and creatine kinase (CK) levels were measured prior to exercise, and 24 and 48 h after exercise. Muscle function (maximal voluntary contraction–MVC) was measured before exercise, immediately after, and 24 and 48 h post-exercise. Groups had no difference on kineanthropometric characteristics and on eccentric exercise performance. They also presented similar baseline values of VAS (0.00 mm for LLLT and placebo groups), LDH (LLLT = 186 IU/l; placebo = 183 IU/l), CK (LLLT = 145 IU/l; placebo = 155 IU/l) and MVC (LLLT = 293 Nm; placebo = 284 Nm). VAS data did not show group by time interaction (P = 0.066). In the other outcomes, LLLT group presented (1) smaller increase on LDH values 48 h postexercise (LLLT = 366 IU/l; placebo = 484 IU/l; P = 0.017); (2) smaller increase on CK values 24 h (LLLT = 272 IU/l; placebo = 498 IU/l; P = 0.020) and 48 h (LLLT = 436 IU/l; placebo = 1328 IU/l; P < 0.001) post-exercise; (3) smaller decrease on MVC immediately after exercise (LLLT = 189 Nm; placebo = 154 Nm; P = 0.011), and 24 h (LLLT = 249 Nm; placebo = 205 Nm; P = 0.004) and 48 h (LLLT = 267 Nm; placebo = 216 Nm; P = 0.001) post-exercise compared with the placebo group. In conclusion, LLLT treatment before eccentric exercise was effective in terms of attenuating the increase of muscle proteins in the blood serum and the decrease in muscle force.

By: Baroni BM, Leal Junior EC, De Marchi T, Lopes AL, Salvador M, Vaz MA

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We tested if modulation in mRNA expression of COX-1 and COX-2 can be related to protective effects of phototherapy in skeletal muscle. Thirty male Wistar rats were divided into five groups receiving either one of four laser doses (0.1, 0.3, 1.0 and 3.0 J) or a no-treatment control group. Laser irradiation (904 nm, 15 mW average power) was performed immediately before the first contraction for treated groups. Electrical stimulation was used to induce six tetanic tibial anterior muscle contractions. Immediately after sixth contraction, blood samples were collected in order to evaluate CK activity and muscles were dissected and frozen in liquid nitrogen in order to evaluate mRNA expression of COX-1 and COX-2. The 1.0 J and 3.0 J groups showed significant enhancement (p<0.01) in total work performed in 6 tetanic contractions compared to control group. All laser groups, except the 3.0 J group, presented significantly lower post-exercise CK activity than control group. Additionally, 1.0 J group showed increased COX-1 and decreased COX-2 mRNA expression compared to control group and 0.1, 0.3 and 3.0 J laser groups (p<0.01). We conclude that preexercise infrared laser irradiation with dose of 1.0 J enhances skeletal muscle performance and decreases post-exercise skeletal muscle damage and inflammation.

By: de Almeida P, Lopes-Martins RA, Tomazoni SS, Silva Jr JA, de Tarso Camillo de Carvalho P, Bjordal JM, Leal Junior EC

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The aim of this work was to evaluate the effects of low-level laser therapy (LLLT) on exercise performance, oxidative stress, and muscle status in humans. A randomized double-blind placebo-controlled crossover trial was performed with 22 untrained male volunteers. LLLT (810 nm, 200 mW, 30 J in each site, 30 s of irradiation in each site) using a multi-diode cluster (with five spots – 6 J from each spot) at 12 sites of each lower limb (six in quadriceps, four in hamstrings, and two in gastrocnemius) was performed 5 min before a standardized progressive-intensity running protocol on a motor-drive treadmill until exhaustion. We analyzed exercise performance (VO(2 max), time to exhaustion, aerobic threshold and anaerobic threshold), levels of oxidative damage to lipids and proteins, the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the markers of muscle damage creatine kinase (CK) and lactate dehydrogenase (LDH). Compared to placebo, active LLLT significantly increased exercise performance (VO(2 max) p = 0.01; time to exhaustion, p = 0.04) without changing the aerobic and anaerobic thresholds. LLLT also decreased post-exercise lipid (p = 0.0001) and protein (p = 0.0230) damages, as well as the activities of SOD (p = 0.0034), CK (p = 0.0001) and LDH (p = 0.0001) enzymes. LLLT application was not able to modulate CAT activity. The use of LLLT before progressive-intensity running exercise increases exercise performance, decreases exercise-induced oxidative stress and muscle damage, suggesting that the modulation of the redox system by LLLT could be related to the delay in skeletal muscle fatigue observed after the use of LLLT.

By: De Marchi T, Leal Junior EC, Bortoli C, Tomazoni SS, Lopes-Martins RA, Salvador M

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Photobiomodulation (PBM) also known as low-level level laser therapy is the use of red and nearinfrared light to stimulate healing, relieve pain, and reduce inflammation. The primary chromophores have been identified as cytochrome c oxidase in mitochondria, and calcium ion channels (possibly mediated by light absorption by opsins). Secondary effects of photon absorption include increases in ATP, a brief burst of reactive oxygen species, an increase in nitric oxide, and modulation of calcium levels. Tertiary effects include activation of a wide range of transcription factors leading to improved cell survival, increased proliferation and migration, and new protein synthesis. There is a pronounced biphasic dose response whereby low levels of light have stimulating effects, while high levels of light have inhibitory effects. It has been found that PBM can produce ROS in normal cells, but when used in oxidatively stressed cells or in animal models of disease, ROS levels are lowered. PBM is able to up-regulate anti-oxidant defenses and reduce oxidative stress. It was shown that PBM can activate NF-kB in normal quiescent cells, however in activated inflammatory cells, inflammatory markers were decreased. One of the most reproducible effects of PBM is an overall reduction in inflammation, which is particularly important for disorders of the joints, traumatic injuries, lung disorders, and in the brain. PBM has been shown to reduce markers of M1 phenotype in activated macrophages. Many reports have shown reductions in reactive nitrogen species and prostaglandins in various animal models. PBM can reduce inflammation in the brain, abdominal fat, wounds, lungs, spinal cord.

By: Michael R Hamblin

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Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase – CK and alanine) and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy (1H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (~−9 s), decreased O2 deficit (~ −10 L), increased the VO2 from the slow component phase (~+348 ml min−1) and increased the time limit of exercise (~+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance.

By: Cleber Ferraresi, PhD, Thomas Beltrame, MSc, Fernando Fabrizzi, MSc, Eduardo Sanches Pereira do Nascimento, PhD, Marlus Karsten, PhD, Cristina de Oliveira Francisco, MSc, Audrey Borghi-Silva, PhD, Aparecida Maria Catai, PhD, Daniel Rodrigues Cardoso, PhD, Antonio Gilberto Ferreira, PhD, Michael R. Hamblin, PhD, Vanderlei Salvador Bagnato, PhD, and Nivaldo Antonio Parizotto, PhD

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Background/purpose: The action of low-level laser therapy (LLLT) on pericytes during wound healing is not well established. The objective of this study was to identify the effect of laser treatment on pericytes during tissue repair.

Methods: Punch biopsies were performed on 40 Wistar rats. Twenty animals had their wounds treated with a dose of 4 J/cm(2) using a 670 nm diode laser (9 mW output, 0.031 W/cm(2)) every other day, while the controls received sham irradiation. Animals were sacrificed 3, 7, 10 and 14 days after punch biopsy. Immunohistochemistry staining with anti-desmin, antismooth muscle alpha-actin and anti-NG2 antibodies was used to characterize and count pericytes around blood vessels and myofibroblasts dispersed in the extracellular matrix (ECM). The morphology of pericytes was confirmed by transmission electronic microscopy.

By: Medrado A, Costa T, Prado T, Reis S, Andrade Z

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Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to vstimulate, heal, and regenerate damaged tissue. Both pre-conditioning (light delivered to muscles before exercise) and PBM applied after exercise can increase sports performance in athletes. This review covers the effects of PBM on human muscle tissue in clinical trials in volunteers related to sports performance and in athletes. The parameters used were categorized into those with positive effects or no effects on muscle performance and recovery. Randomized controlled trials and case-control studies in both healthy trained and untrained participants, and elite athletes were retrieved from MEDLINE up to 2016. Performance metrics included fatigue, number of repetitions, torque, hypertrophy; measures of muscle damage and recovery such as creatine kinase and delayed onset muscle soreness. Searches retrieved 533 studies, of which 46 were included in the review (n=1045 participants). Studies used single laser probes, cluster of laser-diodes, LED-clusters, mixed clusters (lasers and LEDs), and flexible LED arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle mass gained after training, and decrease inflammation and oxidative stress in muscle biopsies. We raise the question of whether PBM should be permitted in athletic competition by international regulatory authorities.

By: Cleber Ferraresi, Ying-Ying Huang, and Michael R. Hamblin

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Free radicals (FR) are molecules regularly produced by the body, leading to tissue injury or toxic compounds to tissues, and its accumulation results in tissue injury, DNA damage, and cellular dysfunction [1, 2]. The FR are responsible for damages caused by the oxidative stress and show accumulative effects that might contribute to the development of diseases such as diabetes, arteriosclerosis, and cancer [3, 4]. Physical exercise promotes the rise on the FR formation in function of the increment on the oxygen intake. Nevertheless, exercise training engenders adaptations able to unstiffen the damaging effects triggered by FR [5].

By: Helenita Antonia de Oliveira, Ednei Luiz Antonio, Gisela Arsa, Eduardo Tadeu Santana, Flávio André Silva, Daniel Arruda Júnior, Simone dos Santos, Paulo de Tarso Camillo de Carvalho, Ernesto Cesar Pinto Leal-Junior, Amanda Araujo, Kátia De Angelis, Danilo Sales Bocalini, José Antonio Silva Junior, Paulo José Ferreira Tucci, and Andrey Jorge Serra

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Scientific interest in sports recovery modalities has been increasing in recent years. Several studies have been investigating the effects of modalities on subjective outcomes such as post-exercise well-being, objective outcomes such as physical performance, and surrogate outcomes such as biochemical markers related to recovery

By: Ernesto Cesar Pinto Leal-Junior, PhD, PT

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This review discusses the application of He-Ne laser irradiation to injured muscles at optimal power densities and optimal timing, which was found to significantly enhance (twofold) muscle regeneration in rats and, even more, in the cold-blooded toads. Multiple and frequent (daily) application of the laser in the toad model was found to be less effective than irradiation on alternate days. It was found that in the ischemia/reperfusion type of injury in the skeletal leg muscles (3 h of ischemia), infrared Ga-Al-As laser irradiation reduced muscle degeneration, increased the cytoprotective heat shock proteins (HSP-70i) content, and produced a twofold increase in total antioxidants. In vitro studies on myogenic satellite cells (SC) revealed that phototherapy restored their proliferation. Phototherapy induced mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) phosphorylation in these cells, probably by specific receptor phosphorylation. Cell cycle entry and the accumulation of satellite cells around isolated single myofibers cultured in vitro was also stimulated by phototherapy. Phototherapy also had beneficial effects on mouse, rat, dog and pig ischemic heart models. In these models, it was found that phototherapy markedly and significantly reduced (50-70%) the scar tissue formed after induction of myocardial infarction (MI). The phototherapeutic effect was associated with reduction of ventricular dilatation, preservation of mitochondria and elevation of HSP- 70i and ATP in the infarcted zone. It is concluded that phototherapy using the correct parameters and timing has a markedly beneficial effect on repair processes after injury or ischemia in skeletal and heart muscles. This phenomenon may have clinical applications.

By: Oron U.

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Context: Recent studies suggest the prophylactic use of low-powered laser/light has ergogenic effects on athletic performance and postactivity recovery. Manufacturers of highpowered lasers/light devices claim that these can produce the same clinical benefits with increased power and decreased irradiation time; however, research with high-powered lasers is lacking.

Objective: To evaluate the magnitude of observed phototherapeutic effects with 3 commercially available devices.

Design: Randomized double-blind placebo-controlled study.

By: Thiago De Marchi, MSc, PT; Vinicius Mazzochi Schmitt; Carla Danúbia da Silva Fabro; Larissa Lopes da Silva; Juliane Sene; Olga Tairova, PhD; Mirian Salvador, PhD

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Many diseases and traumatic events involving tissue damage are injurious because of ischemia, a sudden or more gradual process characterized by deprivation of the tissues of life-sustaining oxygen. Ischemic heart disease and ischemic stroke account for the largest burden of mortality and morbidity in modern life. The term pre-conditioning (PC) was first applied to a regimen in which repetitive short episodes of ischemia and reperfusion could lead to the development of resistance of the myocardium to a subsequent ischemic insult (heart attack) (Das and Das, 2008). A novel treatment strategy to counter ischemic cardiac disease and stroke developed which was termed ischemic pre-conditioning IPC) (Koch et al, 2014).

By: Tanupriya Agrawal, Gaurav K. Gupta, Vikrant Rai, James D. Carroll, Michael R. Hamblin

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In animal and clinical trials low-level laser therapy (LLLT) using red, infrared and mixed wavelengths has been shown to delay the development of skeletal muscle fatigue. However, the parameters employed in these studies do not allow a conclusion as to which wavelength range is better in delaying the development of skeletal muscle fatigue. With this perspective in mind, we compared the effects of red and infrared LLLT on skeletal muscle fatigue. A randomized double-blind placebo-controlled crossover trial was performed in ten healthy male volunteers.

By: de Almeida P, Lopes-Martins RA, De Marchi T, Tomazoni SS, Albertini R, Corrêa JC, Rossi RP, Machado GP, da Silva DP, Bjordal JM, Leal Junior EC

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Background: Standard treatment of Stress fracture includes rest, compression, elevation and passive stretching. Low level laser therapy (LLLT) has been described in treatment of joint conditions, tendophaties, musculofascial pains and dermatological conditions. A prospective randomized control study was carried out to assess efficacy of LLLT in treatment of stress fractures in tibia.

Method: 68 cases were enrolled. 34 each in control and test group. Control cases were treated with placebo and test group with laser-therapy. Complete resolution of pain and tenderness, and return to painless ambulation was taken as end point of therapy in both groups.

By: Surg Lt Cdr Ashutosh Chauhan, Surg Capt P Sarin

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Low Energy Photon Therapy (LEPT) is a photo-therapeutic modality for pain relief and soft tissue healing acceleration that involves the irradiation of tissue with monochromatic light at intensities that do not cause thermal changes or ionization in tissues. Clinical studies reflected in this review have been performed in Canadian universities, hospitals and clinics during years 1989-2002. This clinical research has been supported by Canadian granting agencies (NRC and DoD of Canada and others). All studies have been performed using a professional system with different single and cluster multiple-sources probes at wavelengths of 660nm, 830nm, 880nm, and 990nm with a range of frequencies of 1-200 Hz, or continuous wave mode. Since 1989 we created three generations of LEPT clinical protocols (using light emitting diodes) for pain relief and carpal tunnel syndrome management. First generation of LEPT clinical protocols had been tested in several prospective, open protocol clinical and case studies involving over 250 subjects with different musculoskeletal and neuromuscular pathologies.

By: N. Filonenko, Ph.D., N. Salansky, Ph.D.

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Pain is the most common reason for physician consultation in the United States. One out of three Americans is affected by chronic pain annually. The number one reason for missed work or school days is musculoskeletal pain. Currently accepted therapies consist of non-steroidal antiinflammatory drugs, steroid injections, opiate pain medications and surgery, each of which carries their own specific risk profiles. What is needed are effective treatments for pain which have an acceptably low risk-profile. For over forty years, low level laser (light) therapy (LLLT) and LED (light emitting diode) therapy (also known as photobiomodulation) has been shown to reduce inflammation and edema, induce analgesia, and promote healing in a range of musculoskeletal pathologies. The purpose of this paper is to review the use of LLLT for pain, the biochemical mechanisms of action, the dose response curves, and how LLLT may be employed by orthopedic surgeons to improve outcomes and reduce adverse events. With the predicted epidemic of chronic pain in developed countries, it is imperative to validate cost-effective and safe techniques for managing painful conditions which would allow people to live active and productive lives. Moreover the acceptance of LLLT (which is currently being used by many specialties around the world) into the armamentarium of the American health care provider would allow for additional treatment options for patients. A new cost-effective therapy for pain could elevate quality of life while reducing financial strains.

By: Howard B Cotler, Roberta T Chow, Michael R Hamblin, and James Carroll

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