Low-Level Light Therapy Research

Desmet KD et al. Clinical and Experimental Applications of NIR-LED Photobiomodulation. Photomedicine and Laser Surgery. 2006, 24(2): 121-128.

  • NIR-LED light represents a novel, non-invasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.
  • In addition, it has been demonstrated that up to 50% of NIR light is absorbed by mitochondrial chromophores, including cytochrome c oxidase
  • Human studies using NIR-LED light therapy have demonstrated greater amounts of epithelialization for wound closure and accelerated healing of skin grafts
  • Genes that were down-regulated in NIR-LED light–treated mice include cytokine receptors, interleukin-1, interleukin-10, and macrophage inflammatory protein–2. A decrease in these genes encoding for proteins associated with the inflammatory response results in a decrease in pain, which in turn increases the ability of tissue-regenerating proteins to facilitate wound closure.
  • NIR-LED light treatment produced a significant reduction in left and right buccal pain (48% and 39%, respectively)

DiDuro J. Neuropathy Patient Satisfaction High with Infrared LED Care. Proceedings of The 10th Annual Conference of the North American Association for Laser Therapy. 2010.

  • 77 patients were surveyed during a course of multimodal care that included IR therapy
  • After an average of 9.6 visits, 90.1% of patients were satisfied with their care

Maegawa Y et al. Effects of Near-Infrared Low-Level Laser Irradiation on Microcirculation. Lasers in Surgery and Medicine. 2000, 27: 427-437

  • LLLI caused potent dilation in the laser-irradiated arteriole, which led to marked increases in the arteriolar blood flow.
  • As a consequence of these changes, the blood flow (Q) showed a rapid initial increase even at ~1 minute after LLLI (increase in the early phase), and continued to increase till 30 minutes after LLLI (increase in the delayed phase), finally leveling off at ~200% of the pre-irradiation value
  • In conclusion, we have shown that laser irradiation at a wavelength of 830 nm is a potent dilator of the arteriole and consequently causes a marked increase in blood flow in the rat microvascular bed. Nitric oxide seems partly involved in the vasodilation that occurs in the early phase.

Ishiguro M, Ikeda K, and Tomita K. Effect of Near-Infrared Light-Emitting Diodes on Nerve Regeneration. J Orthop Sci. 2010, 15:233-239.

  • Our histological study suggests that irradiation with LEDs is advantageous to nerve regeneration.
  • In this study, LEDs at a wavelength of 660 nm effectively promoted peripheral nerve regeneration in our rat model. We propose that this is due to the antioxidative effect induced by LEDs.
  • In the 1-mm section, we observed a significant (approx.. 230%) increase in the LED group compared to that for the controls

Lohr NL et al. Enhancement of Nitric Oxide Release From Nitrosyl Hemoglobin and Nitrosyl Myoglobin by Red/Near-Infrared Radiation: Potential Role in Cardio Protection.

  • The use of far-red and near-infrared light (R/NIR) can reduce infarct size, protect neurons from methanol toxicity, and stimulate angiogenesis.
  • These data suggest that this light source facilitates the release of nitric oxide from nitrosyl heme proteins.
  • In combination, these data suggest that the ability of R/NIR light to liberate nitric NO from tissue stores contributes to cardioprotection and that nitrite, by potentially increasing the size of these NO stores

DeMott TK, Richardson JK, Thies SB, Ashton-Miller JA. Falls and gait characteristics among older persons with peripheral neuropathy. Am J Phys Med Rehabil 2007; 86:125-132.

  • Thirteen of 20 (65%) subjects fell, and 6 of 20 (30%) subjects sustained a fall-related injury during the year of observation.
  • Injuries resulting from falls cost $6 billion per year in the United States.

Whelan HT, et al. DARPA solider self-care: rapid healing of laser eye injuries with light-emitting diode technology. Presented at the RTO HFM Symposium on Combat Casualty Care in Ground-Based Tactical Situations: Trauma Technology and Emergency Medical Procedures. 2004.

  • Photobiomodulation by light in the red to near-infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, and improve recovery from ischemic injury and attenuate degeneration in the injured optic nerve.
  • The prolonged effect of brief NIR-LED treatment implies that it induces a cascade of events leading to the stimulation of gene expression, protein synthesis, and oxidative metabolism.
  • Assessment of the severity of the laser burn-in LED treated and untreated animal demonstrated a greater than 50% improvement in the degree of retinal healing at 1-month post-laser in the LED-treated monkey.
  • The results of this study and others suggest that photobiomodulation with red to near-infrared light augments recovery pathways promoting neuronal viability and restoring neuronal function following injury.

Harkless LB, DeLellis S, Carnegie DH, Burke TJ. Improved foot sensitivity and pain reduction in patients with peripheral neuropathy after treatment with monochromatic infrared photo energy- MIRE. Journal of Diabetes Care and Its Complications 2006; 20: 81-87.

  • Prior to treatment with MIRE, of the 10 tested sites (5 on each foot), 7.1 +/- 2.9 were insensitive to the monofilament 5.07, and 2078 patients (93%) exhibited loss of protective sensation defined by Medicare as a loss of sensation at two or more sites on either foot.
  • After treatment, the number of insensate sites on both feet decreased to 2.4F2.6, an improvement of 66%.
  • After MIRE treatment, the mean pain level was reported to be 2.4 +/- 2.1, a mean reduction of 4.8 points, or 67%.

DeLellis SL, Carnegie DH, Burke TJ. Improved sensitivity in patients with peripheral neuropathy: effects of monochromatic infrared photo energy. Journal of the American Podiatric Medical Association 2005; 95(2): 143-147.

  • After treatment, the mean ± SD number of insensate sites on both feet was 2.3 ± 2.4, an improvement of 71%.
  • In the case of diabetic peripheral neuropathy, there have been no reports of either spontaneous reversal of this condition or efficacy of any nonsurgical intervention.
  • A significant proportion of patients, more than 75%, had well-defined peripheral neuropathy, a condition that would be the least likely to spontaneously reverse or to respond to pharmacologic treatment.

Demura S, Yamaji S, Ikemoto Y. Effect of linear polarized near-infrared light irradiation on flexibility of shoulder and ankle joints. Journal of Sports Medicine and Physical Fitness 2002; 42(4): 438-435.

  • Ranges of shoulder and ankle motions become greater with infrared irradiation and is effective as a warming up method.
  • 10% improvement in ankle and shoulder ROM was seen after a single treatment.
  • The effect of therapy is greater in subjects with lower joint ROM than those with higher.

M.T. Wong-Riley, H.L. Liang, J.T. Eells, B. Chance, M.M. Henry, E. Buchmann, M. Kane, and H.T. Whelan, Photobiomodulation directly benefits primary neurons functionally inactivated by toxins: role of cytochrome oxidase. J Biol Chem 2005; 280 (6): 4761–4771.

  • Evidence has indicated that near-IR light treatment can prevent cell death (apoptosis) in cultured neuronal cells.
  • Recent reports have ascribed the ability of specific wavelengths of light to promote cellular proliferation to the activation of mitochondria, the energy-producing organelles within the cell.
  • Near-IR treatment can also augment mitochondrial function and stimulate antioxidant protective pathways in specific neurons that offer protection against neuronal degeneration.
  • 670nm light pretreatment for 5 minutes (30 J/cm2) twice a day over 3 days attenuated the deficits in locomotor behavior induced by a single injection of MPTP.
  • MPTP has the added advantage in that it poisons the very process thought to account for the beneficial actions of near-IR light—namely, mitochondrial energy production.

Ying R, Liang HL, Whelan HT, Eells JT, Wong-Riley MT. Pretreatment with near-infrared light via light-emitting diodes provided added benefit against rotenone and MPP+ induced neurotoxicity. Brain Research 2008; 1243: 167-168.

  • The goal was to test our hypothesis that pretreatment with near-infrared light (NIR) via light-emitting diode (LED) had a greater beneficial effect on primary neurons grown in media with rotenone or MPP+ than those with or without LED treatment during exposure to poisons.
  • Results indicate that pretreatment with NIR-LED significantly suppressed rotenone- or MPP+-induced apoptosis in both striatal and cortical neurons (P<0.001), and that pretreatment plus LED treatment during neurotoxin exposure was significantly better than LED treatment alone during exposure to neurotoxins.
  • The mechanism of NIR-LED action is the up-regulation of cytochrome c oxidase activity and the production of adenosine triphosphate (ATP).

Wong-Riley MT, Bai X, Buchmann E, Whelan HT. Light-emitting diode treatment reverse the effect of TTX on cytochrome oxidase in neurons. Neurochemistry 2001; 12(14): 3033-3037.

  • Light treatment with a light-emitting diode array at 670 nm (LED) is therapeutic in stimulating cellular events involving increases in cytochrome oxidase activity.
  • 50% of near-infrared light is absorbed by mitochondrial chromophores such as cytochrome c oxidase, which is the terminal enzyme of the electron transport chain. Cytochrome oxidase is an integral membrane protein.
  • The prolonged effect of a brief LED treatment implies that it induces a cascade of events leading to the stimulation of gene expression, protein synthesis, and oxidative metabolism.
  • LED treatment at the parameters used significantly reversed the detrimental effect of TTX on neuronal cytochrome oxidase activity.

Ihsan MFR. Low-level laser therapy accelerates collateral circulation and enhances microcirculation. Photomedicine and Laser Surgery 2005; 23(3): 289-294.

  • The results indicated that LLLT accelerated collateral circulation and enhanced microcirculation and seemed to be unique in the normalization of the functional features of the injured area, which could lead to occlusion of the regional blood vessels.
  • Numerous collateral blood vessels proliferated the area, with marked increases in the diameters of the original blood vessels.
  • Low-level lasers also activate ATP, ATPase, and the conversion of adenosine triphosphate to adenosine. Adenosine stimulates the conversion of cAMP to nitric oxide (NO) or the vascular endothelial growth factor (VEGF).
  • Adenosine, Growth Hormone, Fibroblast Growth Factor, and VEGF are angiogenic factors and promote new vessel growth in the same manner

Schindl A et al. Low-intensity laser irradiation improves skin circulation in patients with diabetic microangiopathy. Diabetes Care 1998; 21(4): 580-584.

  • The data from this first randomized double-blind placebo-controlled clinical trial demonstrate an increase in skin microcirculation due to athermic laser irradiation in patients with diabetic microangiopathy.

Karu TI, Pyatibrat LV, Afaanasyeva NI. Cellular effects of low-power laser therapy can be mediated by nitric oxide. Lasers in Surgery and Medicine 2005; 36: 307-314.

  • NO is involved in the radiation-induced mesenteric arteriolar vasodilatation and the subsequent increase in the microcirculatory blood flow. Irradiation at different wavelengths induces vasodilatation in blood-perfused vessels but not in saline-perfused ones. It was suggested that NO–hemoglobin might serve as a light-sensitive store of NO in red blood cells from which it was released by irradiation.

Gutierrez EM, Helber MD, Dealva D, Ashton-Miller JA, Richardson JK. Mild diabetic neuropathy affects ankle motor function. Clinical Biomechanics 2001; 16: 522-528.

  • Diabetic neuropathy leads to a decrease in rapidly available ankle strength which impairs balance recovery among older women. Younger women demonstrate similar ankle strength but superior balance recovery compared to older women without neuropathy.
  • Others have found that ankle strength is important to balance. Wolfson et al also noted that ankle strength in nursing home residents with a history of falls was about one-tenth that of controls, and that loss of balance during sensory organization test correlated with decreased ankle plantar and dorsiflexion strength.
  • Furthermore, decreased ankle strength has been prospectively identified as a risk factor for falls by Sorock and Labiner.

Bulgher D. Forward of Proceedings of the Second International Conference on Near-Field Optical Analysis: Photodynamic Therapy and Photobiology 2001.

  • Astronaut and cosmonaut experiences have indicated that normal healing of superficial skin wounds is retarded similar to the delayed healing observed during long-term submerged operations on submarines. Photodynamic therapy using near-infrared (NIR) light has been shown to enhance wound repair via several molecular mechanisms, involving absorption by cytochrome C in the mitochondria, enhancement of intracellular signaling, gene expression, and subsequent cytokine secretions.

Whelan HT. The use of NASA light-emitting diode near-infrared technology for biostimulation. Proceedings of the Second International Conference on Near-Field Optical Analysis: Photodynamic Therapy and Photobiology 2001. 32-39.

  • Optimal LED wavelengths include 680, 730 and 880 nm x Near-IR induced a thirty percent increase in the rate of wound closure in these animal models.
  • Light-emitting diodes (LEDs) developed for NASA crewed spaceflight experiments offer an effective alternative to lasers. These diodes can be made to produce multiple wavelengths and can be arranged in large, flat arrays allowing treatment of large wounds.
  • 20% reduction in pain observed when LEDs used on Navy SEAL subjects

Caviness J, Esquilin J, Whelan H. Effect of NASA light-emitting diode on wound healing aboard submerged submarines. Proceedings of the Second International Conference on Near-Field Optical Analysis: Photodynamic Therapy and Photobiology 2001.

  • It is an accepted condition of service aboard U.S. Navy submarines that wounds, burns, and lacerations heal more slowly during submerged operations at sea than they would normally heal if not on board the submarine.
  • The actual analysis of the photographs showed 40% faster healing for the injury treated for 10 days.

Whelan HT, et al. Effect of NASA light-emitting diode irradiation on molecular changes for wound healing in diabetic mice. Journal of Clinical Laser Medicine and Surgery 2003; 21(2): 67-74.

  • The use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/ illness level of activity.
  • In our study, type 2 diabetic mice with excisional skin wounds were treated with LEDs at individual wavelengths of 680 nm, 730 nm, and 880 nm at 4 J/cm2 and 50 mW/cm2. LED treatment produced increased healing rates, compared to surgical controls.
  • 25% decrease in wound size in treatment group compared to surgical controls.

Whelan HT, et al. Effect of NASA light-emitting diode irradiation on wound healing. Journal of Clinical Laser Medicine and Surgery 2001; 19(6): 305-314.

  • LED produced in vitro increases of cell growth of 140–200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155–171% of normal human epithelial cells.
  • LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis.

Zhang R, et al. Near-infrared light protects cardiomyocytes from hypoxia and reoxygenation injury by a nitric oxide-dependent mechanism. J Mol Cell Cardiol 2009; 46(1)

  • Our results demonstrate that exposure to NIR at the time of reoxygenation protects neonatal rat cardiomyocytes and HL-1 cells from injury.
  • The protective effect of NIR is related to NO
  • NIR increases NO, partially independent of NOS
  • Mitochondria have been identified as trigger and effector organelles in cardioprotection by ischemic and pharmacologic preconditioning and postconditioning [46]. COX (complex IV) is the terminal component of the electron transport chain, oxidizing its electron donor cytochrome c and reducing oxygen to water. It has been recognized as a photoacceptor in the NIR range with absorption peaks at 680, 760, and 820 nm, and implicated to be directly involved in photobiomodulation [14,15,48,49]. NIR at 670 and 830 nm partially reversed COX activity in primary neurons after inhibition with KCN, an inhibitor of complex IV. These actions resulted in preserved cellular ATP content and decrease in neuronal death [14].

Swislocki A, et al. A randomized clinical trial of the effectiveness of photon stimulation on pain, sensation, and quality of life in patients with diabetic peripheral neuropathy. Journal of Pain and Symptom Management 2010; 39(1): 88-99.

  • Significant decreases, over time, were found in some pain quality scores, and significant improvements in sensation were found in patients who received the treatment.
  • 76.2% of IR therapy group reported improvement compared to 53.4% of the placebo group. (Treatment group nearly 23% more likely to report decreased pain than placebo)

Prendergrast JJ, Miranda G, Sanchez M. Improvement of sensory impairment in patients with peripheral neuropathy. Endrocrine Practice 2004; 10: 24-30.

  • All patients obtained improvement in sensory impairment in comparison with baseline CPT measures, and 16 of the 27 patients achieved normal sensory responses in all nerve fiber subpopulations.
  • The SWM test is widely used, and the failure to sense the SWM 5.07 is clinically recognized as highly predictive of foot ulceration and lower extremity amputation
  • Average reduction in VAS pain scale was from 8 to 3.
  • In the medical literature, however, no evidence suggests that DPN spontaneously reverses.
  • Because enhanced circulation is produced by some near-infrared devices as well as the ATS system, a microcirculatory increase seems to be the most plausible mechanism of action with respect to improvement in sensory perception noted in this study

Leonard DR, Farooqi MH, Myers S. Restoration of sensation, reduced pain, and improved balance in subjects with diabetic peripheral neuropathy. Diabetes Care 2004. 27: 168-172.

  • Nearly 50% pain reduction noted after 12 treatments
  • At entry 90% of subjects reported substantial balance impairment, after treatment, this decreased to 17%.

Powell MW, Carnegie DE, Burke TJ. Reversal of diabetic peripheral neuropathy and new wound incidence: the role of MIRE. Adv Skin Wound Care 2004; 17: 295-300.

  • After reversal of diabetic peripheral neuropathy following treatment with infrared therapy, only 1 in 68 patients studied developed a new diabetic foot wound.
  • This was an incidence of 1.5% compared to 7.3% in the diabetic population

Powell MW, Carnegie DH, Burke TJ. Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases falls and the fear of falling and improves activities of daily living in seniors. Age and Ageing 2006; 35: 11-16.

  • Overall, reversal of peripheral neuropathy in a clinician’s office and subsequent use of MIRE™ at home was associated with a 78% reduction in falls, a 79% decrease in balance-related fear of falling, and a 72% increase in ADLs.

Kochman AB, Carnegie DH, Burke TJ. Symptomatic reversal of peripheral neuropathy in patients with diabetes. Journal of the American Podiatric Medical Association 2002; 92(3): 125-130.

  • On the basis of Semmes-Weinstein monofilament values, 48 subjects (98%) exhibited improved sensation after 6 treatments, and all subjects had improved sensation after 12 treatments.
  • After 12 MIRE treatments, 9 of 12 (75%) subjects with type 1 diabetes converted from impaired hot-versus-cold sensation to an intact ability to discriminate hot from cold (Table 1), and 4 of 11 (36%) subjects with type 2 diabetes were able to discriminate hot versus cold after 12 MIRE treatments.

Arnall DA et al. The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus. Acta Diabetol 2006; 43: 26-33.

  • PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS.