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Role of Low-Level Laser Therapy in Neurorehabilitation

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


LLLT is steadily moving into mainstream medical practice. As the Western populations
continue to age, the incidence of the degenerative diseases of old age will only continue to
increase and produce an evermore severe financial and societal burden. Moreover, despite
the best efforts of “big pharma,” distrust of pharmaceuticals is growing in general because of
uncertain efficacy and troublesome adverse effects. LLLT has no reported adverse effects,
and no reports of adverse events can be directly attributed to laser or light therapy. We
believe that the high benefit:risk ratio of LLLT should be better appreciated by medical
professionals in the rehabilitation and physical medicine specialties. The introduction of
affordable LED devices powered by rechargeable batteries will lead to many home-use
applications of LLLT. The concept of “wearable” light sources is not far off. Moreover, the
particular benefits of LLLT to both the central and peripheral nervous systems suggest that
much wider use of LLLT could or should be made in cases of both brain diseases and

PM R. 2010 December ; 2(12 Suppl 2): S292–S305. doi:10.1016/j.pmrj.2010.10.013.



LLLT delivered at low doses tends to work better than the same wavelength
delivered at high levels, which illustrates the basic concept of biphasic
dose response or hormesis (Calabrese 2001b). In general, fluences of
red or NIR as low as 3 or 5 J/cm2 will be beneficial in vivo, but a large dose
like 50 or 100 J/cm2 will lose the beneficial effect and may even become
detrimental. The molecular and cellular mechanisms LLLT suggest that
photons are absorbed by the mitochondria; they stimulate more ATP production
and low levels of ROS, which then activates transcription factors,
such as NF-κB, to induce many gene transcript products responsible for
the beneficial effects of LLLT. ROS are well known to stimulate cellular
proliferation of low levels, but inhibit proliferation and kill cells at high
levels. Nitric oxide is also involved in LLLT, and may be photo-released
from its binding sites in the respiratory chain and elsewhere. It is possible
that NO release in low amounts by low dose light may be beneficial, while
high levels released by high dose LLLT may be damaging. The third possibility
is that LLLT may activate transcription factors, upregulating protective
proteins which are anti-apoptotic, and generally promote cell survival.
In contrast, it is entirely possible that different transcription factors
and cell-signaling pathways, that promote apoptosis, could be activated
after higher light exposure. We believe that further advances in the mechanistic
understanding of LLLT will continue to be made in the near
future. These advances will lead to greater acceptance of LLLT in mainstream
medicine and may lead to LLLT being used for serious diseases
such as stroke, heart attack and degenerative brain diseases. Nevertheless
the concept of biphasic dose response or LLLT hormesis (low levels of
light are good for you, while high levels are bad for you) will remain.

Dose-Response, 7:358–383, 2009


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