ArticlePDF Available

Abstract and Figures

Traumatic and non-traumatic injuries are common complications in the aging adult. Inflammation is related to aging in older individuals and may lead to an increased risk of mortality, reduced muscle strength, and decreased mobility. Unresolved inflammation could be related to the origin of many chronic diseases associated with aging such as autoimmune and neurodegenerative diseases or tumors. With any injury to the body there is initially process of inflammation and wound healing that in large number of cases are related with pain that increases in the following days. On the other hand, chronic inflammation in high percentage of cases are related to chronic pain, very common symptoms in aging. Chronic inflammation is associated with normal and pathological aging. Surgery, orthopedic fixation, pharmaceutical therapies and physiotherapy can be used to the treatment of the pathologies and injured area. Here we review the use of gallium arsenide (GaAs)-based near-infrared lightemitting diodes (LEDs) as a coadjutant therapy to control inflammation and wound healing. GaAs-based near infrared LED therapy can be used alongside surgery, orthopedic fixation and pharmaceutical treatments. Studies have shown it to be an effective therapy for the treatment of inflammation and to speed wound healing. This review of clinical observations highlights the capability of GaAs-based LEDs to accelerate wound healing and avoid inflammation.
Content may be subject to copyright.
Healthy Aging Research | Ibe et al. 2015 | 4:24
The role of near-infrared light-emitting diodes in aging adults related to
Onyekachi Ibe 1,2, Erin Morency 3, Pablo Sosa 4, Lori Burkow-Heikkinen 5*
1 School of Engineering, Wayne State University, MI, USA 2 School of Engineering, DeVry University Southfield, MI, USA 3 School of
Nursing, Oakland University, Human Health Building, Rochester, MI, USA 4 Department of Neuroscience, Clinical and Surgical
Neurology, School of Medicine, National University of Cuyo, Centro Universidad, Mendoza, Argentina 5 American College of Sports
Medicine, Indianapolis, IN, USA
Traumatic and non-traumatic injuries are common complications in the aging adult. Inflammation is related to
aging in older individuals and may lead to an increased risk of mortality, reduced muscle strength, and decreased
mobility. Unresolved inflammation could be related to the origin of many chronic diseases associated with aging
such as autoimmune and neurodegenerative diseases or tumors. With any injury to the body there is initially a
process of inflammation and wound healing that in large number of cases are related with pain that increases in
the following days. On the other hand, chronic inflammation in high percentage of cases are related to chronic
pain, very common symptoms in aging. Chronic inflammation is associated with normal and pathological aging.
Surgery, orthopedic fixation, pharmaceutical therapies and physiotherapy can be used to the treatment of the
pathologies and injured area. Here we review the use of gallium arsenide (GaAs)-based near-infrared light-
emitting diodes (LEDs) as a coadjutant therapy to control inflammation and wound healing. GaAs-based near-
infrared LED therapy can be used alongside surgery, orthopedic fixation and pharmaceutical treatments. Studies
have shown it to be an effective therapy for the treatment of inflammation and to speed wound healing. This
review of clinical observations highlights the capability of GaAs-based LEDs to accelerate wound healing and
avoid inflammation.
Citation: Ibe O, Morency E, Sosa P, Burkow-Heikkinen L (2015) The role of near-infrared light-emitting diodes in aging adults related
to inflammation. Healthy Aging Research 4:24. doi:10.12715/har.2015.4.24
Received: December 19, 2014; Accepted: January 28, 2015; Published: April 10, 2015
Copyright: © 2015 Ibe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Competing interests: The authors have declared that no competing interests exist.
* Email:
An LED is an electronic device component that emits
light when electricity passes through it. LEDs are
mostly is monochromatic, occurring at a single
wavelength. The LED light spectrum output can range
from ultra violet to red. The ultraviolet and blue colors
are about 400 nm, while the red color is about 700
nm. LED infrared emission can be greater than 830
nm and these types of LED devices are called Infrared
Emitting Diodes (IRED). LEDs function by
electroluminescence, a visible light production by an
exposed substance to an electrical field with non-
thermal energy generation. Gallium arsenide (GaAs)
is a common semiconductor material used for near-
infrared LEDs, but other semiconductors are also
used. Aluminum gallium indium phosphide (AlGaInP)
and other semiconductor compounds in groups III-V
of the periodic table have also been utilized.
Low-level laser therapy and near-infrared LEDs have
similar effects on inflammation and wound healing.
Some studies have demonstrated that near-infrared
LED is more efficient at speeding up wound healing
compared to laser therapy [3-7]. Near-infrared (NIR)
LED therapy has been shown to improve
inflammation and accelerate wound healing, as well as
Healthy Aging Research | Ibe et al. 2015 | 4:24
helping to control pain. NIR-LED devices for light
therapy are affordable, portable and easy to use,
unlike other light therapy sources, such as lasers or
incandescent light. Furthermore, they have improved
dramatically in quality since the late 1990s, when they
had rather unstable power outputs and divergent
wavelengths. Older generation NIR-LEDs were not
able to produce a meaningful clinical reaction to
tissues. A new generation of NIR LEDs, also called
the “NASA LEDs”, developed by Whelan et al., have
a lower divergence and also a more stable power
output [8].
For NIR-LEDs to be most effective it is important that
they have an appropriate wavelength for the target
cell. Recent literature suggests a wavelength of 830
nm for all aspects of wound healing, pain, anti-
inflammatory treatment and skin rejuvenation.
According to Kim et al., if the wavelength is
incorrect, absorption will be suboptimal and,
according to the Grotthus-Draper law of
photobiology, there can be no reaction without
Photon intensity, or power density (W/cm2), should
be sufficient for the retention of enough photons to
achieve the desired result. If the intensity is too high,
photon energy will be undesirably transformed into
heat in the targeted tissue.
Finally, Kim et al. the fluency or dosage must be
adequate (J/cm2). According to the Bunsen-Roscoe
law of reciprocity, if the power density is too low,
prolonging irradiation time to achieve an ideal energy
density or dose will most likely not give a good final
result [9].
Traumatic head and body injury, surgical procedure,
and metabolic ulcers are common in the aging
population. Each of these, and a variety of other
conditions prevalent in the elderly, lead to a systemic
response to injury. As aging progresses, the body's
ability to respond to injury decreases. Inflammation in
aging is characterized by increased inflammatory
cytokines, decreased adaptation and defective tissue
repair. Research into coadjutant therapies for
pharmaceutical interventions needs to focus on
enhancing the body's response mechanism and NIR-
LEDs have shown positive results.
NIR-LED therapy has shown tremendous possibilities
in anti-photo aging using non-thermal radiation. The
radiation components in the NIR-LED device help
improve the anti-inflammatory elements of cell
rejuvenation treatments [10]. The mitochondria theory
on aging states that oxidative stress, caused by
mitochondria DNA mutations, is associated with
decreased ATP production leading to cellular
degeneration. An experiment conducted by
Kokkinopoulos and his team show a significant
mitochondrial shift in vitro using a 670nm light
exposure and the result showed that aging related
retinal inflammation can be reduced significantly with
the application of light therapy of 670nm [ 11]. There
are other NIR-LED therapy devices for anti-aging
with the range of 940nm and above but more clinical
research needs to be done on these devices.
Vascularized living tissue responds to injury (caused
by infections, chemicals or physical agents, immune
reactions and other methods) by becoming inflamed.
Inflammation is intended to contain and isolate the
damage, destroy microorganisms and inactivate
toxins, and prepare tissues for repair and wound
healing. Although inflammation is fundamentally a
protective response, it can also be harmful since it can
cause severe hypersensitivity reactions or an
inexorable and progressive organic lesion by chronic
inflammation and subsequent fibrosis. Inflammation
can be modulated by different biological, chemical
and physical agents. The wide variety of drugs used in
the treatment of inflammation are well known, as well
as physical agents, such as cold and light. The latter,
in particular photomodulation through NIR-LEDs, has
been demonstrated to have a positive effect in
reducing inflammation and promoting the acceleration
of wound healing and skin rejuvenation. NIR-LED
therapeutic devices are non-coherent, which means the
light intensity is consistent and can spread, covering
larger areas of the tissue. NIR-LED therapies have
short wavelengths and, based on our studies and
literature cited, the shorter the wavelength the deeper
the penetration of light to the tissues. NIR-LEDs are
affordable, portable, easy to use, and continue to
provide viable applications in medicine, for example,
to reduce edema, the migration of inflammatory cells,
and the production of inflammatory cytokines, as well
as accelerating the regeneration of connective tissues.
There are no known risk factors for addiction with this
Healthy Aging Research | Ibe et al. 2015 | 4:24
type of treatment. The length of time the radiation
therapy needs to be applied for optimal outcomes has
yet to be determined.
Extensive review of the English and Spanish literature
was performed using PubMed, BioMed, and Google
Scholar scientific databases. The literature search
included articles relating to light emitting diode, low
level laser therapy in aging.
Inflammation and wound healing
The timeline for wound healing depends greatly on
the level of inflammation. During 2009 1.8 million
patients, in the United States, were discharged from
hospitals for wound care and management [12]
following a range of causes of injury including gait
disturbances; decreased muscle mass; metabolic
diseases; heart disease; and traumatic brain injury [13-
29], Table 1 shows conditions that increase risks for
injury in the aging. All of these may be common
events in the aging population. Aging results in
chronic low grade inflammation that is associated
with increased risk for disease, poor physical
functioning, and mortality.
Table 1. Potential causes for injury of the aging adult [13-29]
Exercise and fitness
Physical Abuse
Metabolic diseases
Heart disease
Arterial Ischemia
Venous disease
Traumatic brain
Traumatic spinal
cord injury
Surgical wounds
Tooth extractions
Traffic collisions
Medical prosthesis
Bone Fracture
Ligament strain
Skin Infection
Inflammation and tissue response to injury is
characterized by acute and chronic phases. In the
acute phase, changes in vascular caliber and
permeability occur with the consequent migration of
leukocytes, particularly neutrophils. Increased
vascular permeability is induced in various ways, one
of which is via chemical mediators such as histamine,
interleukin (IL)-1, and tumor necrotic factor (TNF), as
well as by the migration of leukocytes, and the release
of reactive oxygen species (ROS) and proteolytic
Both IL-1 and TNF facilitate increased vascular
permeability and migration of lymphocytes, enabling
the phenomena of acute inflammation and increased
interstitial fluid. The application of near-infrared light
on tissue in the acute phase of inflammation causes a
decrease in the levels of both IL-1 and TNF-α [30,31].
During acute inflammation, the release of chemical
mediators modulates vascular and cellular phenomena
such as chemotaxis, leukocyte activation,
phagocytosis and release of leukocyte products. An
early mediator released in the area of injury is
histamine, released primarily from mast cells, which
causes vasodilation. Stimulation via near-infrared
LEDs, or low-level lasers, has the ability to modulate
the number of mast cell degranulations [32-34].
Leukocyte activation facilitates the release of pro-
inflammatory molecules, such as the production of
cytokines and metabolites of arachidonic acid. One of
the key enzymes in the production of arachidonic acid
derivatives, such as prostaglandins and thromboxanes,
is cyclooxygenase-2 (COX-2). The activity of this
enzyme can be decreased in areas of inflammation by
stimulation with near-infrared light. Furthermore, the
participation of neutrophils and macrophages in the
acute stage of inflammation allows both phagocytosis
to be initiated, and the release of products from
phagolysosomes into the interstitial space, which can
damage tissue [35,36].
Key products released primarily by macrophages are
growth factors and ROS, which cause tissue damage
and the inactivation of anti-proteases. Irradiation with
near-infrared lasers has been shown to decrease the
number of neutrophils and macrophages at the site of
inflammation, and reduces ROS levels at both
neutrophils and the damaged tissues [37-40]. Nitric
oxide (NO) is a mediator that has some protective
effects during acute phase inflammation. Some of
these effects are to maintain vascular tone and reduce
leukocyte recruitment. Studies have shown NO levels
can be increased by stimulation with near-infrared
light [41-43]. Finally, if the injurious agent can be
Healthy Aging Research | Ibe et al. 2015 | 4:24
eliminated, the regulatory mechanisms of the
inflammatory process can occur, leading to tissue
regeneration. If the offending agent is not properly
removed it can lead to chronic inflammation.
Chronic inflammation is a lengthy process of weeks to
months, in which active inflammation, tissue
destruction, and attempts at healing occur in a
simultaneous manner. In contrast to acute
inflammation, chronic inflammation is characterized
by the infiltration of mononuclear inflammatory cells,
tissue destruction, and attempts at healing by fibrosis
and angiogenesis. Macrophages are the dominant and
central cells in chronic inflammation; they are
activated by clinical mediators such as interferon-γ,
produced by T-lymphocytes. The application of near-
infrared light significantly inhibits the expression of
interferon-γ and IL-1β, and decreases inflammation by
changing the expression of genes encoding
inflammatory cytokines [44,45]. Macrophage
activation produces chemical mediators that stimulate
tissue repair; in turn, some of these mediators generate
ROS, NO and proteases, which further cause tissue
injury. The concentration of ROS, as well as
metalloproteases, may be decreased in the damaged
tissue by stimulation with near-infrared light. In
addition, tissue repair mediators such as transforming
growth factor (TGF)-β1 and platelet-derived growth
factor (PDGF), can be modulated by light [40,46-48].
Finally, in chronic inflammation, infiltration of
mononuclear cells into the tissues generates tissue
destruction and attempts at healing tissue.
Aging is associated with various changes in the
inflammatory response. As humans age there is an
upregulation in the anti-stress responses, both cellular
and molecular, that has been coined 'inflammaging'.
Over time this leads to tissue damage that may lead to
a decrease in effective function of the inflammatory
response. Factors that may also lead to continuous
low-grade inflammation in the elderly include
smoking, subclinical disorders, and increased fat
tissue [49]. Fat tissue may be linked to increased
levels of macrophages, which are associated with
cytokine production [50] Newer studies have found a
correlation between infectious history and an
increased risk of heart attack, stroke, and cancer [51]
suggest that infections at early ages leave an imprint
in the host and inflammatory mechanisms can become
flawed, and lead to further diseases during later years.
If an individual's body is adept in keeping
inflammatory cytokines low, or anti-inflammatory
cytokines high, they have a greater chance of attaining
higher ages [52-54].
As humans age the functionality of the mitochondria
decreases; both in effectiveness and by the increase of
free radicals. Free radicals are known to increase pro-
inflammatory signals that lead to cell death or
uncontrolled cell growth has identified these
mitochondrial deficiencies as a cause of chronic
inflammation [55].
Diets high in red meat may also lead to an
accumulation of antibodies for the Neu5Gc sugar
molecule found in red meats, and enters human tissue
after consumption. The human immune system sees
this sugar as a foreign invader and creates antibodies.
Over time, the combination of this foreign invader and
the antibodies causes an inflammatory state that may
become chronic [56].
Healing and tissue regeneration is the final process of
tissue injury, and involves a large number of cells and
chemical mediators. In tissue repair, it is known that
various processes are activated to achieve tissue
regeneration or healing, including the proliferation
and migration of parenchymal cells of connective
tissue, angiogenesis, synthesis of extracellular matrix
(ECM) proteins, and tissue remodeling. The main
connective tissue cells involved in tissue regeneration
are fibroblasts. These cells, by stimulation with near-
infrared light, can increase in activity and number.
Their effects are modulated, in part, by increasing
mediators such as TGF-β1 and PDGF [57-60]. It is
also known that stem cells are involved in tissue
regeneration; these can also be stimulated by near-
infrared light, causing an increase in both number and
activity [61,62]. One of the most important factors in
the process of angiogenesis - a critical component of
wound healing - is vascular endothelial growth factor
(VEGF). Both VEGF and angiogenesis can be
stimulated by near-infrared light [63]. Tissue
continuity is rebuilt by fibroblasts and endothelial
cells. Fibroblasts rebuild the matrix, while endothelial
cells are needed for angiogenesis. Collagen,
particularly Types I and III, is needed to ensure
successful wound healing. As the repair progresses,
fibroblasts synthesize and deposit collagen and other
ECM proteins such as decorin. Levels of these
Healthy Aging Research | Ibe et al. 2015 | 4:24
molecules can be increased by stimulation with light
[64-66]. Collagen deposition and the composition of
the ECM is remolded by metalloproteases. These
enzymes generate a balance between the synthesis and
degradation of molecules to achieve adequate
regeneration and tissue healing. Metalloproteases can
be modulated by near-infrared light [67,68].
Effect of lasers and LEDs on pathological
In our experience, inflammation caused by tooth
extraction, repetitive micro-injury to the tendons,
shoulder pain caused by playing golf, acute tennis
elbow pain, and chronic pain of the quadriceps tendon
after swimming, all saw an improved range of motion
and decreased pain after treatment with 940 nm NIR
LEDs. Another study looking at patient recovery after
surgical procedures in various locations (Achilles
tendon, shoulder, wrist, etc.) showed that infrared
light increased the rate of wound healing by 25-35%
Chronic inflammation in aging is characterized by
increased inflammatory cytokines, decreased
adaptation, and defective tissue repair in response to
injury. Many pathologies are related with aging
process are mediated by the inflammatory process
and, of these, osteoarthritis is among those affecting
the highest number of patients. Oshima et al. observed
that the application of NIR-LEDs to an osteoarthritis
animal model increased Type II collagen expression
and decreased TNF-α expression. This therapy can
decrease levels of inflammation in the osteoarthritic
joints [71]. A reduction in the number of
polymorphonuclear cells and signs of inflammation
was also observed in the treatment of joint
inflammation using near-infrared light therapy [72].
Rheumatoid arthritis is another important illness that
causes significant disability. Monocyte chemotaxis
protein (MCP)-1 is a key chemokine in the
inflammatory status of this disease. Kuboyama el al.
demonstrated that NIR-LED irradiation significantly
reduced MCP-1 gene expression in a rheumatoid
arthritis rat model, thus reducing inflammation [73].
TNF-α and IL-6 are also important mediators in
rheumatoid arthritis; studies in animal arthritis models
have shown that stimulation with near-infrared light
can reduce the levels of both [73,74].
Near-infrared light therapy may have potential
applications as a noninvasive treatment. It has been
suggested that low-level lasers and NIR-LED
irradiation can modulate inflammatory processes,
inhibiting edema formation, vascular permeability and
hyperalgesia, and suppress inflammation in the
synovial membrane [75,76]. In a recent study in an
experimental tendinitis rat model, treatment with near-
infrared LEDs once per day in the same location on
the tendon, showed an increase in the amount of
collagen Types I and III between days seven and 14.
Increased collagen implies increased fiber
organization and wound healing [77]. In a study of
soccer players with second-degree ankle sprains,
results showed that treatment with an 820 nm
aluminum gallium indium phosphide (GaAlAs) diode
laser, alongside conventional RICE (rest, ice,
compression, and elevation), decreased edema after 24
and 48 hours with no recurrence. When range of
motion in patients with tendinopathy was studied,
patients treated with light therapy showed an average
improvement of 32% compared to controls [78].
Xavier et al. studied the effects of NIR-LED therapy
on Achilles tendinitis induced by collagenase in a rat
model. The group treated with an 880 nm near-
infrared LED showed fewer inflammatory cells
arriving at the injury site, and reduced mRNA
expression of IL-1β, IL-6, TNF-α, and COX-2 [79].
NIR-LED therapy may therefore have therapeutic
benefits in reducing signs of inflammation in
tendinitis. Near-infrared light therapy has also been
shown to reduce the pain and increase the diminished
range of joint motion typically seen in tennis elbow
and epicondylitis, with no bony structure involvement
[80]. The application of near-infrared light also
accelerates healing following tenotomy of the tendon
Some studies have shown that near-infrared light
therapy can reduce inflammation in injuries of the
nervous tissue. Moreira et al. (2009) studied the effect
of near-infrared light in animal models with brain
injury. They observed that, during the first few hours
following brain injury, low-level laser phototherapy
can modulate brain levels of TNF-α, IL-1β and IL-6.
Along with other studies, this shows that stimulation
with near-infrared light decreases inflammation in
Healthy Aging Research | Ibe et al. 2015 | 4:24
injured brains while also stimulating reconnection of
the injured areas [82,83].
In spinal cord lesions, it has been observed that the
use of 810 nm light treatment in animal models can
increase axonal numbers and decrease the activation
of immune cells and cytokines [84]. Using an animal
model to study a nerve lesion, NIR-LED phototherapy
reduced edema, the number of mononuclear cells
present in the inflammatory infiltration, and increased
nerve regeneration [85]. Albarracin et al. found that
near-infrared photobiomodulation in albino rats
resulted in decreased retinal degeneration, presumably
from reduced cell death, inflammation, and decreased
microglia [86]. The sciatic nerve crush model was
performed on mice while under anesthesia. Seven
days after the operation, NIR-LED irradiation therapy
(950 nm, 80 mW/cm2, 2.5 J/cm2) began - applied to
the skin at the site of injury - and continued for 15
days. In both the spinal cord and sciatic nerve TNF-α
levels decreased, but IL-1β and IL-10 levels did not
change compared to the control [87]. Khalil et al.
studied the role of free radicals and NO in delayed
recovery in aged rats with nerve injury. The results
suggest that ROS and neuronal NO contribute to
delayed recovery of injured nerves in old rats. The
results also raise the notion that possible interaction of
free radicals with NO to form peroxynitrite might be
responsible for such delayed recovery. In previous
paragraphs we describe that ROS may be decreased in
the damaged tissue by stimulation with near-infrared
light and could be an interesting coadjuvant therapy in
these types of lesions [88].
Cerebrovascular disease is the third leading cause of
death and the leading cause of serious long-term
disability in the Western hemisphere [89]. Endothelial
dysfunction is characterized by a chronic alteration of
inflammatory function and markers of inflammation
and the innate immune response, including C-reactive
protein, IL-6 and TNF-α are linked to the occurrence
of myocardial infarction and stroke in healthy elderly
populations [90]. Near-infrared light therapy is an
emerging technology that could be used in
combination with other therapies to treat
cerebrovascular disease [91]. Moreira et al. (2011)
observed the effects of phototherapy on wound
healing following cerebral ischemia by cryogenic
injury. They showed that the irradiated lesions lost
less tissue than the control, had a significantly higher
number of viable neurons, and the lesions of irradiated
animals had fewer leukocytes and lymphocytes. They
concluded that laser phototherapy was able to control
brain damage, thus leading to wound healing
following cryogenic injury [92]. Another study by
Shen et al. investigated the effects of irradiation from
a low-level laser applied to rat models with stroke.
They observed the proliferation and differentiation of
adipose tissue-derived stem cells in neuronal cells.
The results of Western blot analysis indicated a
significant increase in nestin and oligo-2,
demonstrating that low-level laser irradiation exerts a
positive effect on the differentiation of stem cells and
can be employed to treat ischemic stroke to regain
motor functions [93].
The inflammatory process plays an important role in
some skin diseases. For some skin conditions NIR-
LED therapy has shown bactericidal and anti-
inflammatory effects [94-96]. As for other
inflammatory skin diseases, a study performed in
patients with psoriasis found anti-inflammatory
effects when using 830 nm and 633 nm NIR-LED
therapy [97]. In animal models of serositis it was
observed that the application of near-infrared light
therapy reduced inflammation in peritonitis and
pleurisy by reducing inflammatory cell migration
Near-infrared light therapy may accelerate cutaneous
wound healing in different pathological conditions
such as diabetes, and burned or injured skin. This
accelerated process was observed in association with a
photobiomodulation-related increase of healing
mediators such as integrins, laminin, kinesin, TGF-β1
and matrix metalloproteinase-2. Photobiomodulation
stimulated healing, relieved pain and inflammation,
restored function of tissue, and helped to control
secondary infection [100-106]. The wounds of
patients treated with a 670 nm, 720 nm, and 880 nm
near-infrared LED unit healed twice as quickly as
their counterparts not treated with near-infrared.
Following tissue injury, adequate inflammatory
vascular responses are essential for subsequent tissue
repair. Khodr et al. studied the role of ROS and age in
modulating the inflammatory response in acute and
chronic injury conditions and the implications of this
modulation for tissue repair. The results showed that
antioxidant treatment had no effect on the response
during early and late phases of acute inflammation in
Healthy Aging Research | Ibe et al. 2015 | 4:24
young rats. However in old rats, the vascular response
was significantly attenuated (60%) or significantly
increased (40%) during the early and late phases of
acute inflammation, respectively. The results suggest
that ROS have a paradoxical role exerting either a
positive or negative effect on the inflammatory
response with age. Related with this observation, the
ROS can be modulated by NIR-LED as we observe
previously in the text [107]. The potential for fracture
and bone injury in the aging adult is high due to gait
disturbances, daily activities, age more than 75, living
alone, chronic pain, metabolic diseases, and
nutrition/vitamin deficits. Bone healing has also been
shown to benefit from light therapy [108,109].
Pinheiro et al. demonstrated that bone irradiated with
near-infrared light showed increased osteoblastic
proliferation, collagen deposition, and bone
neoformation [110]. Rats given a ligature injury at the
first mandibular molar were treated with NIR-LED
irradiation, and histomorphological analysis revealed
decreased bone resorption, lower neutrophil
migration, and lower TNF levels [111].
Pharmacological therapy is widely used to modulate
inflammation and wound healing, but NIR-LED GaAs
therapy is emerging as a promising non-
pharmacological coadjutant treatment for these
conditions. Some studies have compared the effect of
light therapy with that of the most commonly used
drugs for inflammation and wound healing. De
Almeida et al. compared the effects of the topical
application of sodium diclofenac with low-laser
therapy on morphological aspects and the gene
expression of biochemical inflammatory markers.
Compared to subjects given diclofenac, those
receiving light therapy showed decreased expression
of COX-2 and TNF-α, and improved morphological
aspects of the tissue [112]. A similar study by de
Paiva Carvalho et al. observed that, compared with
the topical and intramuscular application of
diclofenac, near-infrared light therapy more
effectively decreased the levels of prostaglandin E2
during the treatment of acute muscle strain injury
[113]. Viegas et al. observed that low-level laser
therapy showed a higher degree of collagen fiber
organization and maturation, and a better healing
pattern than that seen with the use of meloxicam, but
meloxicam more effectively decreased the intensity of
polymorphonuclear infiltration and edema in rat
wounds [114]. Finally, some studies have compared
the effects of near-infrared light therapy with those of
corticosteroids. These have observed that, compared
to corticoids, light therapy increases collagen content,
allows a better arrangement of the ECM, an increase
in number of fibroblasts, and accelerated levels of
epithelialization. Near-infrared light accelerates tissue
repair even in the presence of dexamethasone [115-
117]. Other physical therapy use on the treatment of
wound healing is ultrasound. A study by Demir et al.
compared the effects of laser, ultrasound, and
combined laser and ultrasound treatments in
experimental tendon healing. They concluded that
both treatments increased tendon healing biochemical
and biomechanical more than the control groups. No
statistically significant difference was found between
ultrasound and laser therapy and these therapies can
be used successfully in the treatment of tendon
healing [118].
Many diseases of the elderly, such as Alzheimer's
disease, could benefit from NIR-LED therapy studies.
The injury to the brain during the progression of
Alzheimer's disease is also compounded by
inflammation and studies should be completed to
understand the effects of NIR-LED therapy on
Alzheimer's inflammation [49].
Finally, aging and many pathologies related to aging,
are closely associated to inflammatory processes and
are the target of many therapeutic options, often with
undesirable side effects. NIR-LED is emerging as an
adjunctive treatment option without adverse effects,
which makes it an interesting option in adult patient
who frequently consume too many drugs which could
help decrease, or not potentiate, adverse effects. NIR-
LED can exert therapeutic effects at different stages of
the inflammatory process and tissue repair. This
makes it a therapeutic option of great interest for
clinical application and research for its promising
modulatory effects at the molecular level.
GaAs-based NIR-LEDs represent a novel, non-
invasive, and effective coadjutant therapeutic
intervention for the treatment of numerous diseases
linked to inflammation and wound healing. The
equipment is easy to obtain, economically more sound
Healthy Aging Research | Ibe et al. 2015 | 4:24
than other methods of NIR radiation, can be used
several times during the day, simple to use with little
training, and versatile for use in many fields and
The authors acknowledge the help of Jeffrey Dikin.
1. Khatami M. Inflammation, aging, and cancer:
tumoricidal versus tumorigenesis of immunity: a
common denominatormapping chronic diseases. Cell
Biochem Biophys. 2009;55(2):55-79.
2. Rottenberg Y, Jacobs JM, Stessman J. Prevalence of
pain with advancing age brief report. J Am Med Dir
Assoc. 2015;16(3):264.
3. Pagin MT, de Oliveira FA, Oliveira RC, Sant'Ana AC,
de Rezende ML, Greghi SL, et al. Laser and light-
emitting diode effects on pre-osteoblast growth and
differentiation. Lasers Med Sci. 2014;29(1):55-9.
4. Oliveira Sampaio SC, de C Monteiro JS, Cangussú MC,
Pires Santos GM, dos Santos MA, dos Santos JN, et al.
Effect of laser and LED phototherapies on the healing of
cutaneous wound on healthy and iron-deficient Wistar
rats and their impact on fibroblastic activity during
wound healing. Lasers Med Sci. 2013;28(3):799-806.
5. El-Bialy T, Alhadlaq A, Felemban N, Yeung J, Ebrahim
A, H Hassan A. The effect of light-emitting diode and
laser on mandibular growth in rats. Angle Orthod.
6. Dall Agnol MA, Nicolau RA, de Lima CJ, Munin E.
Comparative analysis of coherent light action (laser)
versus non-coherent light (light-emitting diode) for
tissue repair in diabetic rats. Lasers Med Sci.
7. Klebanov GI, Shuraeva NIu, Chichuk TV, Osipov AN,
Vladimirov IuA. Comparison of the effects of laser and
light-emitting diodes on lipid peroxidation in rat wound
exudate. Biofizika. 2006;51(2):332-9.
8. Whelan HT, Houle JM, Whelan NT, Donohoe DL,
Cwiklinski J, Schmidt MH, et al. NASA light-emitting
diode medical program-progress in space flight and
terrestrial applications. Space Technology and
Applications International Forum. 2000;504:37-43.
9. Kim WS, Calderhead RG. Is light-emitting diode
phototherapy (LED-LLLT) really effective? Laser Ther.
10. Pinar Avci, Asheesh Gupta, Magesh Sadasivam, Daniela
Vecchio, Zeev Pam, Nadav Pam, Michael R
Hamblin:Low-level laser (light) therapy (LLLT) in skin:
stimulating, healing, restoring Semin Cutan Med Surg.
2014 August 8. Published in final edited form as: Semin
Cutan Med Surg. 2013;32(1):41-52.
11. Kokkinopoulos I1, Colman A, Hogg C, Heckenlively J,
Jeffery G.Age-related retinal inflammation is reduced by
670 nm light via increased mitochondrial membrane
potential.Neurobiol Aging. 2013;34(2):602-9.
12. Crane NJ, Elster EA. Vibrational spectroscopy; a tool
being developed for the noninvasive monitoring of
wound healing. J biomed Opt. 2012; 17(1):010902.
13. Kallinen M, Markku A. Agingin, physical activity and
sports injuries. An overview of common sports injuries
in the elderly. Sports Med. 1995;20(1):41-52.
14. Murphy K, Waa S, Jaffer H, Sauter A, Chan A. A
literature review of findings in physical elder abuse. Can
Assoc Radiol J. 2013;64(1):10-4.
15. Nakajima K, Anzai E, Iwakami Y, Ino S, Yamashita K,
Ohta Y. Measuring gait pattern in elderly individuals by
using a plantar pressure measurement device. Technol
Health Care. 2014;22(6):805-15.
16. Gazibara T, Pekmezovic T, Tepavcevic DK, Tomic A,
Stankovic I, kostic VS et al. Circumstances of falls and
fall-related injuries among patients with Parkinson's
disease in an outpatient setting. Geriatr Nurs.
17. Czernuszenko A. Risk factors for falls in post-stroke
patients treated in a neurorehabilitation ward. Neurol
Neurochir Pol. 2007;41(1):28-35.
18. Gerasimchuk PA, Kisil' PV, Vlasenko VG, Pavlyshin
AV. Endothelial dysfunction indicators in patients with
diabetic foot syndrome. Vestn Ross Akad Ned Nauk.
19. Mitchell RJ, Lord SR, Harvey LA, Close JC. Obesity
and falls in older people: mediating effects of disease,
sedentary behavior, mood, pain, and medication use.
Arch Gerontol Geriatr. 2015;60(1):52-8.
20. Gist S, Tio-Matos I, Falzgraf S, Cameron S, Beebe M.
wound care in the geriatric client. Clin Interv Aging.
21. Lohr NL, Ninomiya JT, Warltier DC, Weihrauch D. Far
red/near infrared light treatement promotes femoral
artery collateralization in the ischemic hindlimb. J Mol
Cell Cardiol. 2013;62:36-42.
22. Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier
J, Hamblin MR, et al. Significant improvements in
cognitive performance post-transcranial, red/near-
infrared light-emitting diode treatments in chronic, mild
traumatic brain injury: open-protocol study. J
Neurotrauma. 2014;31(11):1008-17.
23. Con J, Friese RS, Long DM, Zangbar B, O'Keeffe T,
Joseph B, et al. Falls from ladders; age matters more
than height. J Surg Res. 2014;191(2):262-7.
24. Mosenthal AC, Livingston DH, Lavery RF, Knudson
MM, Lee S, Morabito D, et al. The effect of age on
functional outcome in mild traumatic brain injury; 6-
Healthy Aging Research | Ibe et al. 2015 | 4:24
month report of a prospective multicenter trial. J
Trauma. 2004;56(5):1042-8.
25. Xai ZS, Huang JM, Zhuang XR, Chen SB, Wu SQ, Yao
ZD, et al. Case-control stud on suture-assisted locking
plate for the treatment of proximal humeral fractures in
elderly. Zhongguo Gu Shang. 2014;27(12):1015-8.
26. Liu JJ, Ruan HJ, Wang JG, Fan CY, Zeng BF. Double-
column fixation for type C fractures of the distal
humerus in the elderly. J Shoulder Elbow Surg.
27. Diaz-Garcia RJ, Oda T, Shauver MJ, Chung KC. A
systematic review of outcomes and complications of
treating unstable distal radius fractures in the elderly. J
Hand Surg am. 2011;36(5):824-35.
28. Holt G, Smith R, Duncan K, Hutchison JD, Gregori A,
Reid D. Outcome ater sequential hip fracture in the
elderly. J Bone Joint Surg Am. 2012;94(19):1801-8.
29. Siennicki-Lantz A, Elmståhl. Phenomenon of declining
blood pressure in elderly-high systolic levels are
undervalued with Korotkoff method. BMC Geriatr
30. Fernandes KP, Alves AN, Nunes FD, Souza NH, Silva
JA Jr, Bussadori SK, et al. Effect of photobiomodulation
on expression of IL-1β in skeletal muscle following
acute injury. Lasers Med Sci. 2013;28(3):1043-6.
31. Mesquita-Ferrari RA, Martins MD, Silva JA Jr, da Silva
TD, Piovesan RF, Pavesi VC, et al. Effects of low-level
laser therapy on expression of TNF-α and TGF-β in
skeletal muscle during the repair process. Lasers Med
Sci. 2011;26(3):335-40.
32. Vasheghani MM, Bayat M, Rezaei F, Bayat A,
Karimipour M. Effect of low-level laser therapy on mast
cells in second-degree burns in rats. Photomed Laser
Surg. 2008;26(1):1-5.
33. Khoshvaghti A, Zibamanzarmofrad M, Bayat M. Effect
of low-level treatment with an 80-Hz pulsed infrared
diode laser on mast-cell numbers and degranulation in a
rat model of third-degree burn. Photomed Laser Surg.
34. Sawasaki I, Geraldo-Martins VR, Ribeiro MS, Marques
MM. Effect of low-intensity laser therapy on mast cell
degranulation in human oral mucosa. Lasers Med Sci.
35. Albertini R, Aimbire F, Villaverde AB, Silva JA Jr,
Costa MS. COX-2 mRNA expression decreases in the
subplantar muscle of rat paw subjected to carrageenan-
induced inflammation after low level laser therapy.
Inflamm Res. 2007;56(6):228-9.
36. Pires D, Xavier M, Araújo T, Silva JA Jr, Aimbire F,
Albertini R. Low-level laser therapy (LLLT; 780 nm)
acts differently on mRNA expression of anti- and pro-
inflammatory mediators in an experimental model of
collagenase-induced tendinitis in rat. Lasers Med Sci.
37. Dos Santos SA, Alves AC, Leal-Junior EC, Albertini R,
Vieira Rde P, Ligeiro AP, et al. Comparative analysis of
two low-level laser doses on the expression of
inflammatory mediators and on neutrophils and
macrophages in acute joint inflammation. Lasers Med
Sci. 2014;29(3):1051-8.
38. Alves AC, Vieira R, Leal-Junior E, dos Santos S,
Ligeiro AP, Albertini R, et al. Effect of low-level laser
therapy on the expression of inflammatory mediators
and on neutrophils and macrophages in acute joint
inflammation. Arthritis Res Ther. 2013;15(5):R116.
39. Huang YY, Nagata K, Tedford CE, McCarthy T,
Hamblin MR. Low-level laser therapy (LLLT) reduces
oxidative stress in primary cortical neurons in vitro. J
Biophotonics. 2013;6(10):829-38.
40. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S,
Sugawara K. Low-level laser irradiation attenuates
production of reactive oxygen species by human
neutrophils. J Clin Laser Med Surg. 2003;21(3):165-70.
41. Poyton RO, Ball KA. Therapeutic photobiomodulation:
nitric oxide and a novel function of mitochondrial
cytochrome c oxidase. Discov Med. 2011;11(57):154-9.
42. Ball KA, Castello PR, Poyton RO. Low intensity light
stimulates nitrite-dependent nitric oxide synthesis but
not oxygen consumption by cytochrome c oxidase:
Implications for phototherapy. J Photochem Photobiol
B. 2011;102(3):182-91.
43. Mitchell UH, Mack GL. Low-level laser treatment with
near-infrared light increases venous nitric oxide levels
acutely: a single-blind, randomized clinical trial of
efficacy. Am J Phys Med Rehabil. 2013;92(2):151-6.
44. Dvashi Z, Sar Shalom H, Shohat M, Ben-Meir D, Ferber
S, Satchi-Fainaro R, et al. Protein phosphatase
magnesium dependant 1A governs the wound healing-
inflammation-angiogenesis cross talk on injury. Am J
Pathol. 2014;184(11):2936-50.
45. Pereira da Silva L, Miguel Neves B, Moura L, Cruz MT,
Carvalho E. Neurotensin decreases the proinflammatory
status of human skin fibroblasts and increases epidermal
growth factor expression. Int J Inflam.
46. Bracey NA, Gershkovich B, Chun J, Vilaysane A,
Meijndert HC, Wright JR Jr, et al. Mitochondrial
NLRP3 protein induces reactive oxygen species to
promote Smad protein signaling and fibrosis
independent from the inflammasome. J Biol Chem.
47. Jiang L, Dai Y, Cui F, Pan Y, Shang H, Xiao J, et al.
Expression of cytokines, growth factors and apoptosis-
related signal molecules in chronic pressure ulcer
wounds healing. Spinal Cord. 2014;52(2):145-51.
48. Moura Júnior Mde J, Arisawa EÂ, Martin AA, Carvalho
JP, da Silva JM, Silva JF, et al. Effects of low-power
LED and therapeutic ultrasound in the tissue healing and
inflammation in a tendinitis experimental model in rats.
Lasers Med Sci. 2014;29(1):301-11.
49. Licastro F, Candore G, Lio D, Porcellini E, Colonna-
Romano G, Franceschi C, et al. Innate immunity and
Healthy Aging Research | Ibe et al. 2015 | 4:24
inflammation in aging: a key for understading age-
related diseases. Immun Ageing. 2005;2:8.
50. Curat CA, Miranville A, Sengenes C, Diehl M, Tonus C,
Busse R, et al. From blood monocytes to adipose tissue-
resident macrophages: induction of diapedesis by human
mature adipoctyes. Diabetes. 2004;53:1285-92.
51. Finch CE, Crimmins EM. Inflammatory exposure and
historical changes in human life-spans. science.
52. Bonafe M, Olivieri F, Cavallone L, Giovagnetti S,
Mayegiani F, Cardelli M, et al. A gender-dependent
genetic predisposition to produce high levels of IL-6 is
detrimental for longevity. Eur J Immunol.
53. Lio D, Scola L, Crivello A, Colonna-Romano G,
Candore G, Bonafe M, et al. Gender0specific
association between -1082 IL-10 promoter
polymorphism and longevity. Genes Immun. 2002;3:30-
54. Lio D, Scola L, Crivello A, Colonna-Romano G,
Candore G, Bonafe M, et al. Inflammation, genetics, and
longevity: further studies on the protective effects in
men of IL-10-1082 promoter SNP and its interaction
with TNF-alpha-308 promoter SNP. J Med Genet.
55. Dinarello CA. A clinical perspective of IL-1β as the
gatekeeper of inflammation. Eur J Immunol.
56. Samraj AN, Pearce OM, Läubli H, Crittenden AN,
Bergfeld AK, Banda K, et al. A red meat-derived glycan
promotes inflammation and cancer progression. Proc
Natl Acad Sci USA. 2015;112(2):542-7.
57. Taniguchi D, Dai P, Hojo T, Yamaoka Y, Kubo T,
Takamatsu T. Low-energy laser irradiation promotes
synovial fibroblast proliferation by modulating p15
subcellular localization. Lasers Surg Med.
58. Vinck EM, Cagnie BJ, Cornelissen MJ, Declercq HA,
Cambier DC. Increased fibroblast proliferation induced
by light emitting diode and low power laser irradiation.
Lasers Med Sci. 2003;18(2):95-9.
59. Byrnes KR, Barna L, Cenault VM, Waynant RW, Ilev
IK, Longo L, et al. Photobiomodulation improves
cutaneous wound healing in an animal model of type II
diabetes. Photomed Laser Surg. 2004;22(4):281-90.
60. Hakki SS, Bozkurt SB. Effects of different setting of
diode laser on the mRNA expression of growth factors
and type I collagen of human gingival fibroblasts. Lasers
Med Sci. 2012;27(2):325-31.
61. Wu HP, Persinger MA. Increased mobility and stem-cell
proliferation rate in Digesia tigrina incuded by 88nm
light emitting diode. J Photochem Photobiol B.
62. Li WT, Chen CW, Huang PY. Effects of low level light
irradiation on the migration of mesenchymal stem cells
derived from rat bone marrow. Conf Proc IEEE Eng
Med Biol Soc. 2013;2013:4121-4.
63. Salate AC, Barbosa G, Gasper P, Koeko PU, Parizotto
Na, Benze BG, et al. Effect of In-Ga-Al-P diode laser
irradiation on angiogenesis in partial ruptures of
Achilles tendon in rats. Photomed Laser Surg.
64. Silveira PC, Silva LA, Freitas TP, Latini A, Pinho RA.
Effects of low-power laser irradiation (LPLI) at different
wavelengths and doses on oxidative stress and
fibrogenesis parameters in an animal model of wound
healing. Lasers Med Sci. 2011;26(1):125-31.
65. Fiório FB, Albertini R, Leal-Junior EC, de Carvalho Pde
T. Effect of low-level laser therapy on types I and III
collagen and inflammatory cells in rats with induced
third-degree burns. Lasers Med Sci. 2014;29(1):313-9.
66. De Souza TO, Mesquita DA, Ferrari RA, Dos Santos
Pinto D Jr, Correa L, Bussadori SK, et al. Phototherapy
with low-level laser affects the remodeling of types I
and III collagen in skeletal muscle repair. Lasers Med
Sci. 2011;26(6):803-14.
67. Guerra Fda R, Vieira CP, Almeida MS, Oliveira LP, de
Aro AA, Pimentel ER. LLLT improves tendon healing
through increase of MMP activity and collagen
synthesis. Lasers Med Sci. 2013;28(5):1281-8.
68. Casalechi HL, Leal-Junior EC, Xavier M, Silva JA Jr, de
Carvalho Pde T, Aimbire F, et al. Low-level laser
therapy in experimental model of collagenase-induced
tendinitis in rats: effects in acute and chronic
inflammatory phases. Lasers Med Sci. 2013;28(3):989-
69. Hsin, J. Weston, J. Treating sports-related injury and
pain with light. Practical Pain Management. 2006;6(7).
70. Bjordal JM, Couppé C, Ljunggren E. Low level laser
therapy For tendinopathy. Evidence of a dose-response
pattern. Physical Therapy Reviews. 2001;6:91-9.
71. Oshima Y, Coutts RD, Badlani NM, Healey RM, Kubo
T, Amiel D. Effect of light-emitting diode (LED)
therapy on the development of osteoarthritis (OA) in a
rabbit model. Biomed Pharmacother. 2011;65(3):224-9.
72. Pallotta RC, Bjordal JM, Frigo L, Leal Junior EC,
Teixeira S, Marcos RL et al. Infrared (810-nm) low-
level laser therapy on rat experimental knee
inflammation. Lasers Med Sci. 2012;27(1):71-8.
73. Kuboyama N, Abiko Y. Reduction of monocyte
chemoattractant protein-1 expression in rheumatoid
arthritis rat joints with light-emitting diode
phototherapy. Laser Ther. 2012;21(3):177-81.
74. Araki H, Imaoka A, Kuboyama N, Abiko Y. Laser
reduction of interleukin-6 expression in human
synoviocytes and rheumatoid arthritis rat joints by linear
polarized near infrared light (Superlizer) irradiation.
Laser Ther. 2011;20(4):293-300.
75. De Morais NC, Barbosa AM, Vale ML, Villaverde AB,
de Lima CJ, Cogo JC, et al. Anti-inflammatory effect of
low-level laser and light-emitting diode in zymosan-
Healthy Aging Research | Ibe et al. 2015 | 4:24
induced arthritis. Photomed Laser Surg. 2010;28(2):227-
76. Amano A, Miyagi K, Azuma T, Ishihara Y, Katsube S,
Aoyama I, et al. Histological studies on the rheumatoid
synovial membrane irradiated with a low energy laser.
Lasers Surg Med. 1994;15(3):290-4.
77. Carrinho PM, Renno AC, Koeke P, Salate AC, Parizotto
NA, Vidal BC. Comparative study using 685-nm and
830-nm lasers in the tissue repair of tenotomized
tendons in the mouse. Photomed Laser Surg.
78. Stergioulas A. Low-level laser treatment can reduce
edema in second degree ankle sprains. J Clin Laser Med
Surg. 2004;22(2):125-8.
79. Xavier M, David DR, de Souza RA, et al. Anti-
inflammatory effects of low-level light emitting diode
therapy on Achilles tendinitis in rats. Lasers Surg Med.
80. Simunovic Z, Trobonjaca T, Trobonjaca Z. Treatment of
medial and lateral epicondylitis - tennis and golfer’s
elbow with LLLT: a multicenter double blind, placebo-
controlled clinical study on 324 patients. J Clin Laser
Med Surg. 1998;16(3):145-51.
81. Casalechi HL, Nicolau RA, Casalechi VL, Silveira L Jr,
De Paula AM, Pacheco, MT. The effects of low-level
emitting diode on the repair process of Achilles tendon
therapy on rats. Lasers Med Sci. 2009;24(4):659-65.
82. Moreira MS, Velasco IT, Ferreira LS, Ariga SK,
Barbeiro DF, Meneguzzo DT, et al. Effect of
phototherapy with low intensity laser on local and
systemic immunomodulation following focal brain
damage in rat. J Photochem Photobiol B.
83. Xuan W, Agrawal T, Huang L, Gupta GK, Hamblin
MR. J Low-level laser therapy for traumatic brain injury
in mice increases brain derived neurotrophic factor
(BDNF) and synaptogenesis. Biophotonics.
84. Byrnes KR, Waynant RW, Ilev IK, Wu X, Barna L,
Smith K, et al. Light promotes regeneration and
functional recovery and alters the immune response after
spinal cord injury. Lasers Surg Med. 2005;36(3):171-85.
85. Serafim KG, Ramos Sde P, de Lima FM, Carandina M,
Ferrari O, Dias IF, et al. Effects of 940 nm light-emitting
diode (LED) on sciatic nerve regeneration in rats. Lasers
Med Sci. 2012;27(1):113-9.
86. Albarracin R, Eells J, Valter K. Photobiomodulation
protects the retina from light-induced photoreceptor
degeneration. Invest Ophthalmol Vis Sci.
87. Cidral-Filho FJ, Martins DF, Moré AO, Mazzardo-
Martins L, Silva MD, Cargnin-Ferreira E, et al. Light-
emitting diode therapy induces analgesia and decreases
spinal cord and sciatic nerve tumour necrosis factor-a
levels after sciatic nerve crush in mice. Eur J Pain.
88. Khalil Z, Khodr B. A role for free radicals and nitric
oxide in delayed recovery in aged rats with chronic
constriction nerve injury. Free Radic Biol Med.
89. Brott T, Bogousslavsky J. Treatment of acute ischemic
stroke. N Engl J Med. 2000;343(10):710-22.
90. Guarner V, Rubio-Ruiz ME. Low-grade systemic
inflammation connects aging, metabolic syndrome and
cardiovascular disease. Interdiscip Top Gerontol.
91. Schellinger PD, Kohrmann M. Near-infrared laser
treatment of acute stroke: from bench to bedside.
Nervenarzt. 2012;83(8):966-974.
92. Moreira MS, Velasco IT, Ferreira LS, Ariga SK,
Abatepaulo F, Grinberg LT, et al. Effect of laser
phototherapy on wound healing following cerebral
ischemia by cryogenic injury. J Photochem Photobiol B.
93. Shen CC, Yang YC, Chiao MT, Chan SC, Liu BS. Low-
level laser stimulation on adipose-tissue-derived stem
cell treatments for focal cerebral ischemia in rats. Evid
Based Complement Alternat Med. 2013;2013:594906.
94. Riddle CC, Terrell SN, Menser MB, Aires DJ,
Schweiger ES. A review of photodynamic therapy
(PDT) for the treatment of acne vulgaris. J Drugs
Dermatol. 2009;8(11):1010-9.
95. Barolet D, Boucher A. Radiant near infrared light
emitting diode exposure as skin preparation to enhance
photodynamic therapy inflammatory type acne treatment
outcome. Lasers Surg Med. 2010;42(2):171-8.
96. Sadick N. A study to determine the effect of
combination blue (415 nm) and near-infrared (830 nm)
light-emitting diode (LED) therapy for moderate acne
vulgaris. J Cosmet Laser Ther. 2009;11(2):125-8.
97. Ablon G. Combination 830-nm and 633-nm light-
emitting diode phototherapy shows promise in the
treatment of recalcitrant psoriasis: preliminary findings.
Photomed Laser Surg. 2010;28(1):141-6.
98. Correa F, Lopes Martins RA, Correa JC, Iversen VV,
Joenson J, Bjordal JM. Low-level laser therapy (GaAs
lambda = 904 nm) reduces inflammatory cell migration
in mice with lipopolysaccharide-induced peritonitis.
Photomed Laser Surg. 2007 Aug;25(4):245-9.
99. Lopes-Martins RA, Albertini R, Martins PS, Bjordal JM,
Faria Neto HC. Spontaneous effects of low-level laser
therapy (650 nm) in acute inflammatory mouse pleurisy
induced by carrageenan. Photomed Laser Surg.
100. Rezende SB, Ribeiro MS, Núñez SC, Garcia VG,
Maldonado EP. Effects of a single near-infrared laser
treatment on cutaneous wound healing: biometrical and
histological study in rats. J Photochem Photobiol B.
101. Whelan HT, Smits RL Jr, Buchman EV, Whelan NT,
Turner SG, Margolis DA, et al. Effect of NASA light-
Healthy Aging Research | Ibe et al. 2015 | 4:24
emitting diode irradiation on wound healing. J Clin
Laser Med Surg. 2001;19(6):305-14.
102. Danno K, Mori N, Toda K, Kobayashi T, Utani A. Near-
infrared irradiation stimulates cutaneous wound repair:
laboratory experiments on possible mechanisms.
Photodermatol Photoimmunol Photomed.
103. Güngörmüş M, Akyol UK. Effect of biostimulation on
wound healing in diabetic rats. Photomed Laser Surg.
104. Oliveira PC, Meireles GC, dos Santos NR, de Carvalho
CM, de Souza AP, dos Santos JN, et al. The use of light
photobiomodulation on the treatment of second-degree
burns: a histological study of a rodent model. Photomed
Laser Surg. 2008;26(4):289-99.
105. Meirelles GC, Santos JN, Chagas PO, Moura AP,
Pinheiro AL. A comparative study of the effects of laser
photobiomodulation on the healing of third-degree
burns: a histological study in rats. Photomed Laser Surg.
106. Min PK, Goo BL. 830 nm light-emitting diode low level
light therapy (LED-LLLT) enhances wound healing: a
preliminary study. Laser Ther. 2013;22(1):43-9.
107. Khodr B1, Khalil Z. Modulation of inflammation by
reactice oxygen species: implications for aging and
tissue repair. Free Radic Biol Med. 2001;30(1):1-8.
108. Barbos Pinheiro AL, Limeira Júnior Fde A, Márquez
Gerbi ME, Pedreira Ramalho LM, Marzola C, Carneiro
Ponzi EA, et al. Effect of 830-nm laser light on the
repair of bone defects grafted with inorganic bovine
bone and decalcified cortical osseous membrane. J Clin
Laser Med Surg. 2003;21(6):383-8.
109. Liu X, Lyon R, Meier HT, Thometz J, Haworth ST.
Effect of lower-level laser therapy on rabbit tibial
fracture. Photomed Laser Surg. 2007;25(6):487-94.
110. Pinheiro AL, Gerbi ME. Photoengineering of bone
repair processes. Photomed Laser Surg. 2006;24(2):169-
111. Carvalho AS, Napimoga MH, Coelho-Campos J, Silva-
Filho VJ, Thedei G. Photodynamic therapy reduces bone
resorption and decreases inflammatory response in an
experimental rat periodontal disease model. Photomed
Laser Surg. 2011;29(11):735-40.
112. De Almeida P, Lopes-Martins RÁ, Tomazoni SS,
Albuquerque-Pontes GM, Santos LA, Vanin AA, et al.
Low-level laser therapy and sodium diclofenac in acute
inflammatory response induced by skeletal muscle
trauma: effects in muscle morphology and mRNA gene
expression of inflammatory markers. Photochem
Photobiol. 2013;89(2):501-7.
113. De Paiva Carvalho RL, Leal-Junior EC, Petrellis MC,
Marcos RL, de Carvalho MH, De Nucci G, et al. Effects
of low-level laser therapy (LLLT) and diclofenac
(topical and intramuscular) as single and combined
therapy in experimental model of controlled muscle
strain in rats. Photochem Photobiol. 2013;89(2):508-12.
114. Viegas VN, Abreu ME, Viezzer C, Machado DC, Filho
MS, Silva DN, et al. Effect of low-level laser therapy on
inflammatory reactions during wound healing:
comparison with meloxicam. Photomed Laser Surg.
115. Gál P, Mokrý M, Vidinský B, Kilík R, Depta F,
Harakalová M, et al. Effect of equal daily doses
achieved by different power densities of low-level laser
therapy at 635 nm on open skin wound healing in
normal and corticosteroid-treated rats. J Lasers Med Sci.
116. Reis SR, Medrado AP, Marchionni AM, Figueira C,
Fracassi LD, Knop LA. Effect of 670-nm laser therapy
and dexamethasone on tissue repair: a histological and
ultrastructural study. Photomed Laser Surg.
117. Pessoa ES, Melhado RM, Theodoro LH, Garcia VG. A
histologic assessment of the influence of low-intensity
laser therapy on wound healing in steroid-treated
animals. Photomed Laser Surg. 2004;22(3):199-204.
118. Demir H, Menku P, Kirnap M, Calis M, Ikizceli I.
Comparison of the effects of laser, ultrasound, and
combined laser + ultrasound treatments in experimental
tendon healing. Lasers Surg Med. 2004;35(1):84-9.
... The near-infrared LED represents a novel, noninvasive, and effective coadjutant therapeutic modality that enhances the natural wound healing process and reduce the risk of infection by promoting biological effects such as decrease of inflammatory cells, increase of fibroblast proliferation, stimulation of angiogenesis, and increase synthesis of collagen depending on irradiation parameters; wavelength and dose. 14,15 The statistical analysis of our study results showed that the mean and SD of LED therapy group pretreatment were 161.14 ± 11.66 mm 2 . There was a significant decrease in the wound surface area after 8 weeks at the end of treatment to 79.54 ± 5.33 mm 2 . ...
Chronic nonhealed wound after below-knee amputation is a serious problem that is faced by the health care team; therefore, there is a need to find an adjuvant therapy to address this problem. The aim of the study is to evaluate the therapeutic efficacy of light-emitting diode (LED) irradiation on chronic nonhealed wound after below-knee amputation using a digitalized method of evaluation by Adobe Photoshop CS5 aided by magnetic lasso tool. Thirty patients with chronic nonhealed wound (≥4 weeks) after below-knee amputation were randomly divided into 2 equal groups, with 15 participants in each. Group A received the LED irradiation for 24 sessions (3 sessions per week) in addition to the standard medical treatment, and the second experimental group (group B) received the standard medical treatment for 8 weeks. Methods of evaluation included the wound surface area: for tracing the wound perimeter using a computerized software. Results showed that both LED irradiation therapy and standard medical treatment were effective in healing the chronic nonhealed wound, but the LED was more effective than standard medical treatment alone. A clear improvement in the results of wound healing surface area was found in group A, with an improvement percentage of 50.63%, when compared with group B, which used the standard medical treatment alone, with an improvement percentage of 43.96%.
... 19 On the other hand, leukocyte activation can also promote the production of arachidonic acid. 41 It is found that NIR LED light at 880 nm can suppress the activity of a key enzyme in the production of arachidonic acid derivatives in the area of inflammation, i.e., cyclooxygenase-2 (COX-2), and can therefore reduce inflammation. 96 An LED therapy has been reported to be effective for treating inflammation, erythema and edema using 630-660 nm LEDs, with E e ! ...
Light emitting diodes (LEDs) have become the main light sources for general lighting, due to their high lumen efficiency and long life time. Moreover, their high bandwidth and the availability of diverse wavelength contents ranging from ultraviolet to infrared empower them with great controllability in tuning brightness, pulse durations and spectra. These parameters are the essential ingredients of the applications in medical imaging and therapies. Despite the fast advances in both LED technologies and their applications, few reviews have been seen to link the controllable emission properties of LEDs to these applications. The objective of this paper is to bridge this gap by reviewing the main control techniques of LEDs that enable creating enhanced lighting patterns for imaging and generating effective photon doses for photobiomodulation. This paper also provides the basic mechanisms behind the effective LED therapies in treating cutaneous and neurological diseases. The emerging field of optogenetics is also discussed with a focus on the application of LEDs. The multidisciplinary topics reviewed in this paper can help the researchers in LEDs, imaging, light therapy and optogenetics better understand the basic principles in each other’s field; and hence to stimulate the application of LEDs in health care.
... Experimental applications have shown macrophage deposition significantly decreased with NIR LED GaAs therapy. Decreased macrophages influence levels of growth factors, cytokines, and CO [3]. Along with these antiinflammatory properties, NIR LED GaAs also has been shown to increase fibroblasts and collagen, reinforcing arterial walls, allowing for better hemodynamic stability [4]. ...
... Patient care also includes keeping skin contact with urine or feces to a minimum, changing briefs as needed. New coadjuvant techniques to the prevention techniques mentioned include near infrared Light Emitting Diode treatment and medical Manuka honey to accelerate wound healing [36][37][38][39][40][41]. More research on both of these therapies should be done in the various age groups that benefit from home care. ...
Full-text available
Home health care is less expensive than other care options, and is beneficial, for young through the elderly. Home health care for the elderly can lead to increased activities of daily living, improved mobility, and cognitive function. For home health care to be effective the health care providers must be proficient and able to meet the needs of the patient. Patients will benefit from a caregiver who is able to see the independence of the patient as a priority, while maintaining safety precautions to avoid any errors, including medications, accidental injury, or any form of abuse. This article details what the home caregiver and provider should know to effectively aide an individual in their home and cites literature on the benefits of home care
Full-text available
Background: The skin is considered to be a radiosensitive organ. Low-level laser therapy (LLLT) known as photobiomodulation is a growing technology used to treat multitude of conditions that require stimulation of the healing process. Aim of the work: The present work was conducted to study the possible biostimulatory effects of LLLT on the skin of gamma irradiated mice. Materials and methods: 264female mice were used in the present experiments were divided into 6 groups: Group (1): Non irradiated control group. Group (2): Laser irradiated group. Group (3.1): One shot gamma irradiated group. Group (3.2): One shot + laser irradiated group. Group (4.1): Cumulative gamma irradiated group. Group (4.2): Cumulative + laser irradiated group. Exposure of the animals to gamma rays was performed using a cesium-137 source. Two modes of exposure were used, a shot modality where the mice were irradiated with a single sub lethal dose of 5 Gy. While in the other mode, the same dose was given in fractionated daily installations of 1 Gy. Treatment of mice with laser was carried out using a computerized scanner emitting He-Ne (CW) at a wavelength of 632.8 nm. The fluence was 5J/cm 2. Histopatho-logical (HP) assessment of skin biopsies derived from the experimental mice was done immediately after each sacrification.Conclusion: LLL therapy accelerates skin regeneration post exposure to ionizing radiation in both shot and cumulative mode. Our conclusions also highlight the biostimulatory effect of He-Ne LLL on hair follicles.
Full-text available
A well known, epidemiologically reproducible risk factor for human carcinomas is the long-term consumption of "red meat" of mammalian origin. Although multiple theories have attempted to explain this human-specific association, none have been conclusively proven. We used an improved method to survey common foods for free and glycosidically bound forms of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), showing that it is highly and selectively enriched in red meat. The bound form of Neu5Gc is bioavailable, undergoing metabolic incorporation into human tissues, despite being a foreign antigen. Interactions of this antigen with circulating anti-Neu5Gc antibodies could potentially incite inflammation. Indeed, when human-like Neu5Gc-deficient mice were fed bioavailable Neu5Gc and challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Such mice are already prone to develop occasional tumors of the liver, an organ that can incorporate dietary Neu5Gc. Neu5Gc-deficient mice immunized against Neu5Gc and fed bioavailable Neu5Gc developed a much higher incidence of hepatocellular carcinomas, with evidence of Neu5Gc accumulation. Taken together, our data provide an unusual mechanistic explanation for the epidemiological association between red meat consumption and carcinoma risk. This mechanism might also contribute to other chronic inflammatory processes epidemiologically associated with red meat consumption.
Full-text available
Aging is associated with immunosenescence and accompanied by a chronic inflammatory state which contributes to metabolic syndrome, diabetes and their cardiovascular consequences. Risk factors for cardiovascular diseases (CVDs) and diabetes overlap, leading to the hypothesis that both share an inflammatory basis. Obesity is increased in the elderly population, and adipose tissue induces a state of systemic inflammation partially induced by adipokines. The liver plays a pivotal role in the metabolism of nutrients and exhibits alterations in the expression of genes associated with inflammation, cellular stress and fibrosis. Hepatic steatosis and its related inflammatory state (steatohepatitis) are the main hepatic complications of obesity and metabolic diseases. Aging-linked declines in expression and activity of endoplasmic reticulum molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the unfolded protein response. These changes predispose aged individuals to CVDs. CVDs and endothelial dysfunction are characterized by a chronic alteration of inflammatory function and markers of inflammation and the innate immune response, including C-reactive protein, interleukin-6, TNF-α, and several cell adhesion molecules are linked to the occurrence of myocardial infarction and stroke in healthy elderly populations and patients with metabolic diseases.
Full-text available
Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2) . Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF) was significantly upregulated by laser treatment in the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ) but not in the perilesional cortex (lesion) at day 7 but not at day 28. Synapsin-1 (a marker for synaptogenesis, the formation of new connections between existing neurons) was significantly upregulated in lesion and SVZ but not DG, at 28 days but not 7 days. The data suggest that the benefit of LLLT to the brain is partly mediated by stimulation of BDNF production, which may in turn encourage synaptogenesis. Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have wider applications to neurodegenerative and psychiatric disorders. Neurological Severity Score (NSS) for TBI mice.
Objective: The aim of this study was to assess histologically the effect of LLLT (lambda830 nm) on the repair of standardized bone defects on the femur of Wistar albinus rats grafted with inorganic bovine bone and associated or not to decalcified bovine cortical bone membrane. Background Data: Bone loss may be a result of :several pathologies, trauma or a consequence of surgical procedures. This led to extensive studies on the process of bone repair and development of techniques for the correction of bone defects, including the use of several types of grafts, membranes and the association of both techniques. There is evidence in the literature of the positive effect of LLLT on the healing of soft tissue wounds. However, its effect on bone is not completely understood. Materials and Methods: Five randomized groups were studied: Group I (Control); Group IIA (Gen-ox((R))); Group IIB (Gen-ox((R)) + LLLT); Group IIIA (Gen-ox((R)) + Gen-derm((R))) and Group IIIB (Gen-ox((R)) + Gen-derm((R)) + LLLT). Bone defects were created at the femur of the animals and were treated according to the group. The animals of the irradiated groups were irradiated every 48 h during 15 days; the first irradiation was performed immediately after the surgical procedure. The animals were irradiated transcutaneously in four points around the defect. At each point a dose of 4 J/cm(2) was given (phi similar to 0.6 mm, 40 mW) and the total dose per session was 16 J/cm(2). The animals were humanely killed 15, 21, and 30 days after surgery. The specimens were routinely processed to wax, serially cut, and stained with H&E and Picrosirius stains and analyzed under light microscopy. Results: The results showed evidence of a more advanced repair on the irradiated groups when compared to non-irradiated ones. The repair of irradiated groups was characterized by both increased bone formation and amount of collagen fibers around the graft within the cavity since the 15(th) day after surgery, through analysis of the osteoconductive capacity of the Gen-ox((R)) and the increment of the cortical repair in specimens with Gen-derm((R)) membrane. Conclusion: It is concluded that LLLT had a positive effect on the repair of bone defect submitted the implantation of graft.
Background: In recent years, scientists have become increasingly interested in the role of the endothelium in the pathogenesis of vascular lesions of various origins, including diabetic patients. Therefore, the aim of the study was to investigate the expression of endothelial dysfunction in patients with diabetic foot syndrome (DFS), by examining the levels of nitric oxide, endothelin-1 levels in the serum, as well as lower limb microcirculation by laser doppler flowmetry. Patients and methods: It was examined 72 patients with diabetic foot syndrome with I-IV degree of lesion (by Meggit- Wagner classification). Neuropathic form was diagnosed in 32 people, ischemic--40 patients. The function of endothelium was studied on the basis of the determination of enzyme-linked immunosorbent NO and endothelin-1 in peripheral blood serum, as well as to assess the state of the microcirculation of the lower limbs by laser doppler flowmetry, using apparatus LACK-02 (Russia). Results: Patients with DFS are marked with endothelial dysfunction, the severity of which depends on the type of diabetes, glycemic level and pathogenic forms of destruction. This is manifested by secretion reducing of vasodilators (NO) and increased synthesis of vasoconstrictors (endothelin-1), which leads to disruption of peripheral hemodynamic. Characteristic changes in the microcirculation are a dramatic violation of endothelium-dependent regulation mechanism, the redistribution of blood towards the nutritional circulation. Also it is showed a significant reduction in reserve capacity of the capillary bed in response to the sample and the occlusal restoration of blood flow during reactive hyperemia. Conclusion: Development of endothelial dysfunction and changes in peripheral hemodynamic in patients with DFS contributes to the emergence and prolongation of necrotic lesions, as well as violation of reparative processes.
Background and objective: Low level laser therapy (LLLT) has been used for the last few years to treat sports injuries. The purpose of this study was to compare three therapeutic protocols in treating edema in second degree ankle sprains, that did not require immobilization with a splint, under placebo-controlled conditions. Study design/Material and Methods: Forty-seven soccer players with second degree ankle sprains, selected at random, were divided into the following groups: The first group (n=16) was treated with the conventional initial treatment (RICE- Rest, Ice, Compression, Elevation-), the second group (n=16) was treated with the RICE method plus placebo laser, and the third group (n=15) was treated with the RICE method plus an 820nm GaA1As diode laser with a radiant power output of 40 mW at 16 Hz. Before the treatment, and 24, 48 and 72 hours later, the volume of the edema was measured. Results: A three by three repeated measures ANOVA with a follow up post hoc test revealed that the group treated with the RICE and an 820nm GaA1As diode laser, statistically presented a significant reduction in the volume of the edema after 24 hours (40. 3 ± 2. 4 ml , p<0. 01), 48 hours (56. 4 ± 3.1 ml, p<0. 002) and 72 hours (65.1 ± 4. 4 ml, p<0.001). Conclusions: LLLT combined with RICE can reduce edema in second-degree ankle sprains.
Background: The epidemiology of chronic pain with advancing age remains poorly established. Although most studies have examined somatic (musculoskeletal and joint) pain, visceral pain (such as headache and abdominal pain) has warranted less attention. We present longitudinal data from age 70 to 90 years concerning chronic musculoskeletal/joint pain, abdominal pain, and headache. Methods: Data was collected by the Jerusalem Longitudinal Study, which is a prospective study of a representative sample from the 1920-1921 birth-cohort living in West Jerusalem. Participants underwent comprehensive assessment at home in 1990, 1998, 2005, and 2010, at ages 70 (n = 460), 78 (n = 763), 85 (n = 1149), and 90 years (n = 394), respectively, and were directly questioned concerning the presence and location of pain. Results: The overall prevalence of pain of any kind at ages 70, 78, 85, and 90 years was 73% (n = 336/460), 81.1% (n = 619/763), 56.3% (n = 647/1149), and 31.2% (n = 123/394), respectively. Pain at younger ages only was associated with female gender, lower educational status, functional dependence, physical inactivity, increased body mass index, loneliness, depression, and poor self-rated health. At ages 70, 78, 85, and 90 years, chronic neck/back pain was present among 41.5%, 58.9%, 30.1%, and 14.6% of participants, respectively; chronic joint pain was present among 43.0%, 60.6%, 45.2%, and 25.2%, respectively. In contrast abdominal pain was less common and disappeared among the oldest old: 14.7%, 13.9%, 1.7%, and 1.5%, respectively, with a similar pattern for headache: 43.3%, 33.5%, 2.1%, and 1.3%. While pain was reported at ≥2 sites by 42.3% and 54.6% at ages 70 and 78 years, respectively, by ages 85 and 90 years, pain was most frequently reported at only 1 site. Conclusions: Visceral pain (headache and abdominal pain) completely disappeared among the oldest old, in contrast to a far smaller decline in somatic (musculoskeletal and joint) pain.
To explore clinical effects of suturing-assisted locking plate in treating elderly proximal humeral fractures. From January 2005 to January 2013, 55 elderly patients with three- and four-part fractures of proximal humeral fractures were divided into treatment group and control group. In treatment group, there were 31 patients including 12 males, and 19 females aged from 65 to 85 with an average of (74.00±5.42) years old, and treated with suturing-assisted locking plates; 19 patients were Neer 3-part fractures, and 12 patients were Neer 4-part fractures of proximal humerus; 23 patients were suffered from low-energy injuries and 8 patients were caused by high-energy injuries. In control group, there were 24 patients including 7 males, and 17 females aged from 65 to 85 with an average of (72.79±5.34) years old, and treated with locking plates; 16 patients were Neer 3-part fractures, and 8 patients were Neer 4-part fractures of proximal humerus; 17 patients were suffered from low-energy injuries and 7 patients were caused by high-energy injuries. Operative time, blood loss during operation, and bone healing time between two groups were observed and compared. Postoperative Neer scoring were used to evaluate recovery of shoulder joint function. All patients were followed up from 6 to 24 months with an average of 16.1 months. In treatment group, blood loss was (495.806±143.150) ml, function of Neer scoring was 22.645±2.443, range of action was 18.194±2.613, anatomy was 7.935±1.504 and total score of Neer scoring was 77.161±8.335; while in control group, blood loss was (641.667±169.851) ml, function of Neer scoring was 13.958±1.989, range of action was 13.083±2.165, anatomy was 5.500±1.978 and total score of Neer scoring was 58.792±7.313. There were sigificant difference between two groups in these indexes. Suturing-assisted locking plate for the treatment of proximal humerus fractures in elderly, has advantages of less blood loss, simple fracture reduction and rapid recovery of shoulder joint, and is a effective method.