BIOSTIMULATING AND METABOLIC EFFECT
(CELL AND TISSUE)
The first effect of laser radiation is responsible to trigger a series of well-defined molecular mechanisms able to activate a series of downstream cellular pathways.
At the cellular level there is a clear enzymatic activation, with an increase in the synthesis of nucleic acids and proteins and with an increase in metabolic turnover. The acceleration of cellular metabolism necessarily leads to an increase in the production of ATP, the fundamental energy currency for the reactions at the base of intracellular life: the result is a greater amount of energy available at the cellular level. In the presence of inflammatory or degenerative processes, this energy reserve ensures an optimization of structural and functional recovery times.
The increase in the share of mitochondrial ATP allows an increase in the proliferation of satellite cells in the muscle, which are promoters of new fibers to replace those necrotized.
The increase of metabolic activity is the reason why the regenerative process is speed up as a consequence of a cascade of photo-chemical reactions activation.
Of course, this is the main effect driven by the activation of endogenous and exogenous chromophores. Secondarily to that, a series of downstream tissue pathways will be activated to produce biological changes in the body.
The most important PBM biological effects are: stimulation of wound healing, stimulation of angiogenesis/vasodilatation, anti-inflammatory effects, analgesic effect and antimicrobial effect; these effects are important to provide a rational application of PBM for the management of pain.
8 are the main Effects in which Laser Therapy has a high beneficial effect:
ANALGESIC EFFECT = Pain management
PBM has been demonstrated to be efficacious to contrast different types of pain, from neuropathic (characterized by the absence of a specific noxious stimulus triggered by lesions in the central or peripheral nervous system or chronic inflammation) to orthodontic and inflammatory pain in joints and lower back of the spine.
The variability in the results between the different condition could be due either to the nociception type, i.e. neuronal fibers activated by inflammatory pain differs from the ones activated in neuropathic pain, or to the anatomical location of the pain and thus to the nociception terminals distribution or proximity to skin surface.
- Indeed, the detailed mechanism of action of PBM on sensory neurons is still elusive; the first site responsible for response could be the mitochondrial respiratory chain.
NO has been identified as possible mediator of PBM analgesic effect in which NO is liberated from intracellular stores (mainly mitochondria) after PBM stimulation, using near NIR wavelengths.
Indeed, NO binds to cytochrome c oxidase (specifically the heme a3 in the active site of the enzyme) inhibiting mitochondrial respiration; after NIR light stimulation, NO is released from cytochrome c oxidase and metabolic rate in mitochondria can increase. So, in this case, NIR light causes a double effect: increasing mitochondrial activity followed by neurotrophic effect mediated by NO - Another possible mechanism: a “laser evoked neuronal voltage variation” (LEVV) in retinal ganglion cells. LEVV is an increase in membrane potential induced by IR light that reaches
action potential level. In these neurons, IR light induces a train of action potentials mediated by
opening of Transient Receptor Vanilloid channels 4 (TRPV4). The activation of these channels
can be due to local increase of temperature induced by IR light. In this paradigm, IR light causes
a train of action potential thus rendering the neuron unable to respond to other stimuli.
OUTCOMES:
Through the controlled tissue hyperemia, a muscle relaxing and elasticizing action is carried out on the myofascial tissues, which result in a decrease in the perception of pain symptoms. In addition, the laser pulse can interfere with the conduction of the painful signal at the peripheral level, through a blockage of the action potential of superficial nerve fibers. Laser therapy is responsible of central pain relief by stopping the transmission of the painful stimulus through the afferent and efferent fibers to the brain with reduced pain perception.
Photobiomodulation increases in the permeability of the plasma membrane to the potassium ion, inducing a partial but concomitant endorphin stimulation of the central nervous system, moreover following laser therapy there is an increase in the production of morphine-mimetic substances, of clear analgesic action (endogenous molecules such as endorphins, encephalin, serotonin, acetylcholine secreted by the brain and adrenal gland). Laser therapy in orthopaedic field:
- arthralgia treatments (both rheumatic and degenerative) such as epicondylitis, polyarthritis, gonalgie with or without effusion, lumbago, sciatica, lumbago, disc herniation, laser therapy (tendinitis, lumbar, back);
- general traumatology (for example, in cases of tendonitis, joint sprains, muscular strains, bursitis, ecchymosis, muscle tears, ulcers and sores, edema, hematomas, osteoarthritis, overload pathologies, traumatic effects);
- rehabilitation (hip, neuromotor, stroke, orthopaedic, femur, hand, meniscus, wrist, shoulder, knee, hip prosthesis, ankle, knee prosthesis, neurocognitive, Parkinson’s);
VASODILATION EFFECT = improved vascular activity
PBM stimulates the proliferation of endothelial cells, resulting in the formation of numerous blood vessels, improved release of nutrients and oxygen, and increased production of granulation tissue. It also promotes vascular smooth muscle relaxation, resulting in capillary vasodilatation, improves drainage liquid from the interstitial space, thus leading to pain relief due to the reduction of local edema.
Indeed, the improved local microcirculation leads to a faster edema reabsorption and a quickening of the lymphatic drainage, promoted even by granulocyte diapedesis.
The mechanism underling the effect of PBM on vasodilatation is the release of histamine, NO and serotonin. As result, a reduction of local ischemia and enhanced perfusion is achieved. PBM effect on vasodilatation increases the passage of nutrients and oxygen to the injured tissues, thus facilitating the repair and the removal of cellular fragments. PBM induced increases in NO, cytokines and growth factors are contributory to this process. Both blood and lymphatic vessels have been studied in vivo describing a significant increase and regeneration after PBM therapy. As circulation and perfusion accelerate and blood vessels diameters enlargement occurs, with a consequent increasing of circulating blood, patients assist to an accelerated tissue repair and healing processes Vasodilation and neo-angiogenesis (opening of new vessels from pre-existing capillaries) are closely related to muscle recovery and reconditioning, as they guarantee an extensive perfusion and therefore oxygen transport to tired or damaged tissues.
In addition, vasodilation (especially capillary vasodilation) provides nutrients and growth factors (such as FGF - fibroblast activation factors and angiogenesis promoter): the subsequent activation of fibroblasts leads to an increase in the synthesis of collagen determinant in the tissue repair process.
Vasodilation is involved in metabolic waste removal (inflammatory factors included) as well as in boosting lymphatic drainage with a reduction in oedemas (local swelling).
THERMAL EFFECT = lymphatic drainage
The photothermal interactions produce a stimulation of the local microcirculation, both haematic and lymphatic, with effect also on the permeability of the endothelium, accelerating the reabsorption of inflammatory effusion and lymphatic peristalsis in the presence of liquid stasis. In Thermal effect by its ISP delivery technology promote the lymphatic system stimulation mediated by Ton/Toff laser activity, allowing to stimulate lymphatic vessels to dilate and promote drenage.
ANTI-INFLAMMATORY EFFECT = wash-out pro-inflammatory markers
PBM is able to improve mast cells degranulation: this effect results in an increased release of histamine, which leads to an acceleration of the inflammatory cascade.
Since after PBM therapy this process develops more rapidly, the healing phase of tissues begins sooner improving the wound healing progression. Since inflammation entails both vascular and cellular events, at the local injured site, reactive components such as mast cells, bradykinins and prostaglandins are triggered. At the same time, the equilibrium of cellular membrane ions concentrations (Ca2+, Na+ and K+), and the proton gradient over the mitochondria membrane, are positively activated by PBM.
This mechanism is performed thanks to beneficial ROS production, which increases the concentrations of intracellular Ca2+ up taking in the mitochondria after PBM. PBM is able to create a shift in the cell redox potential generating greater oxidation, which leads to an increased ROS production and cell redox activity. Since the redox state regulates cellular signaling pathways, variation in the cellular redox state can activate or inhibit them. Due to these changes, several intracellular signaling pathways are activated, such as nucleic acid synthesis, protein synthesis, enzyme stimulation and cell cycle progression.
Furthermore, changes in cellular redox state may also induce transcriptional changes, which lead to the regulation of several transcription factors Anti-inflammatory effect is involved in the reduction of inflammatory cytokines content released post-trauma such as Interleukin 1beta cytokines family (IL-6, IL-8, IL-12, IL-20), Tumor Necrosis factor alpha ( TNF alpha) and many others pro-inflammatory molecules involved in fibrosis transition, muscle actin depolymerization (myostatin, Vimentin-3, Collagen type 4, Cofilin).
The process is moreover mediated by the increase in histamine release, nitric oxide (NO) and serotonin levels acting their beneficial effect to counteract ischemic reduction and perfusion improvement.
The hyperemia generated by laser therapy treatment produces vasodilation at the capillary and lymphatic levels, causing an effect on the distribution of proinflammatory substances in damaged tissues and on the removal of associated catabolites.
The vasodilation of the small vessels also ensures a greater supply of oxygen and nutrients to the injured tissues. The anti-flogistics effect is also achieved by blocking the effects given by the release of ROS in a traumatic injury model.
IMMUNITY ACTIVATION = Immuno-regulatory activity and biomodulation
Immune system modulation is a remarkably event under laser therapeutic session. Laser treatments promotes immune surveillance, cell recruitment and redistribution of T and B lymphocytes upon an injury or as a consequence of tissue lesion. This improvement is extremely important, since immune system cells exert a pivotal role by alerting against an external insult.
Dendritic cells (DC) activation upon laser therapy are responsible to scour body surfaces by engulfing invading pathogens, such as a bacterium. They are APC cells or cells that have antigen, essential for the activation of the specific immune response mediated by lymphocytes. Laser therapy is also targeted to stimulate local Leukocytic activity.
ANTI-MICROBIAL EFFECT = reduction in wound healing primary or secondary infections
It is well known since several years that laser irradiation is able to eliminate bacteria both in vitro and in vivo conditions, using different wavelengths and sources of laser light in the range from 193 nm in the ultraviolet region, emitted by excimer lasers, to 10.6 μm in the far IR region, emitted by CO2 lasers. It is usually believed that the bactericidal action of the laser is due to thermal heating.
In fact, it is known that temperatures above 60°C can cause thermal damage and subsequent killing of bacteria.
Grönqvist et al. demonstrated the antimicrobial effect of Nd:YAG laser (operating in the IR range) on Staphylococcus epidermidis, registering an agar temperature of approximately 70°C. Schoop et al. have explored the antimicrobial effect of four laser systems that employ different wavelengths: 2940 nm (Er:YAG), 2780 nm (Er:YSGG), 1064 nm (Nd:YAG) and 810 nm (diode laser), obtaining significant reductions in Escherichia coli and Enterococcus faecalis viability.
Jawhara et al. conducted a study in vitro and in vivo on wound infections sustained by Escherichia coli using an 810 nm diode laser, showing that bacterial killing depends on laser fluence rather than power density.
Interestingly, they obtained a complete killing of bacteria colonizing infected wounds registering a local temperature of 45°C, while bacteria heated without laser light resisted to temperature increase until 60°C.
The authors hypothesize that chromophores inside bacteria, which may be sensitive to IR light, may cause a local intra-bacterial temperature increase, leading eventually to bacterial death.