Cold Laser for Treating Neuropathy
Cold laser treatments are non-thermal and non-invasive
These treatment effectively mimic solar radiation and result in the production of collagen, Vitamin D, increased epithelial cell activity and capillary blood vessel formation. Treating neuropathy with cold laser directly supports the healing process at the site of compromise. This begins the healing process and promotes natural, drug free PAIN RELIEF.
The stimulation from the cold laser treatment sends messages to the brain to both support healing at the point(s) of treatment, while simultaneously releasing a flood of endorphins. This stimulates an increase in the body's dopamine and seratonin levels. The body starts to heal itself and the pain is significantly reduced. While other forms of treatment may reduce pain, they rarely work towards repairing the compromised tissue, and work towards true healing like the cold laser treatment does. However, for best results and ongoing encouragement of the healing process, regular cold laser therapy treatments are a must.
Dr. Bradley Gipson, DPM wrote:
"Since cold laser treatments stimulate the area inflicted with pain, they often result in anti-inflammatory and immunosuppressive effects. The nerve function is stimulated, the blood supply is essentially increased, and the immune system is afforded an incredible boost, which then allows wound healing as well as almost immediate and long-term pain relief.
Most treatments currently in use for neuropathy are geared towards treating the symptoms and not to cure the problem. These treatments help lessen the symptoms to make the disease more manageable for the patient; however, they usually involve prescription medications that mask the disease rather than treating it. Recent research [see below] has shown that Cold Laser Therapy can help treat the underlying causes of neuropathy and help with symptom management.
Cold Laser Therapy helps by actually stimulating microcirculation around the nerve fibers, which increases blood flow to the nerves and helps to heal and reduce neuropathic pain. Laser light energy penetrates the skin and stimulates increased oxygen on a cellular level. This increase in microcirculation around the nerve has been shown to help regenerate fibers and help heal peripheral nerves. Cold Laser Therapy is painless and has been proven to decrease neuropathy, decrease inflammation and aide in the healing of wounds and tendons."
- from Podiatry Today
Can Low-Level Laser Therapy Have An Impact For Small Fiber Neuropathy?
Kerry Zang, DPM, Janna Kroleski, DPM, Shahram Askari, DPM, and Sanford Kaner, DPM
One would determine the classification of neuropathy by the fiber type that is directly affected. Small fiber neuropathy (SFN) is one prevalent form of neuropathy that affects small fiber sensory neurons.4
More recently, physicians have utilized a nutraceutical approach with promising results. Metanx (Pamlab, LLC) is a prescription nutraceutical, which contains bioavailable forms of L-methylfolate (2.8 mg), pyridoxal 5'-phosphate (25 mg) and methylcobalamin (2 mg) that have been shown to have a positive response in small fiber neuropathy.27 Early preliminary studies have shown regrowth of small nerve fibers after several months of treatment. There are very few adverse effects when utilizing the nutraceutical approach.
Overall though, therapeutic options for SFN are limited with most therapies attempting to address the underlying immune-mediated aspects. The use of simple analgesics, anticonvulsants or antidepressants does not address the important etiologies of SFN, which include ischemia and nerve degeneration. An effective therapeutic approach would promote angiogenesis, downregulate inflammation and induce small fiber nerve regeneration.
A therapy with such promise is low-level laser therapy (LLLT). Researchers have shown that low-level laser therapy promotes: central and peripheral neuron repair; suppression of cyclooxygenase-2 (COX-2); enhancement of peripheral endogenous opioids; upregulation of vascular endothelial growth factor (VEGF); angiogenesis; collagen synthesis and decorin expression during tendon and ligament repair; reduction in fibrosis, suppression of conduction along unmyelinated C fibers; and inhibition of histamine release.28-54
Low-level laser therapy is an emerging technology to help treat and control pain in the lower extremities. Researchers have shown that low-level laser irradiation can have a positive response for tissues that exhibit microvascular compromise and become anoxic secondary to metabolic injury with resulting microvascular inflammation, oxidative injury, and mitochondrial dysfunction. Authors have demonstrated that the more recently developed 17.5 mW 635 nm laser has a positive response on cell membranes, mitochondria and damaged neurologic structures. Lasers of low intensity initiate analgesic, anti-inflammatory and biostimulatory effects, resulting in an increase in local microcirculation and increased healing.55-57 Increasing microcirculation induces an essential function in the tissue repair process and in pain control. This process allows increases in oxygenation and nutritional supply to tissues. This process allows for the expulsion of metabolic byproducts, which may contribute to pain. ( The red is the 650 – the main machine has red lasers with 15 mW – the red probe has 100 mW.)
A Closer Look At The Mechanism Of Action Of Low-Level Laser Therapy
Lasers deliver light in a highly concentrated manner defined by a high degree of spatial and temporal coherence. Lasers involve high-intensity photo-bio stimulation of a medium, which can be a gas, liquid, crystal, dye or semiconductor, resulting in the emission of photons.
The two major categories of laser therapy are class IV and class III, which are differentiated according to output power. Low-level laser therapy is a class III laser and requires only a discrete amount of output intensity or energy (5-500 mW) to yield a clinical response. Power reveals a biphasic dose-response in which higher intensities impede rather than facilitate a cellular and clinical response.58 Low-level lasers operate within the principles of bioorganic photochemistry, a discipline of science that explores the interaction between photons and biochemical pathways in cells.
The clinical utility of low-level laser therapy is derived from the ability to modulate cellular metabolism and influence a diverse array of intracellular biochemical cascades that directly affect cellular behavior and function.
The biological effect of coherent laser irradiation on cells is termed photobiomodulation. All light is radiation energy that is measured in discrete units called photons and its effect on cellular components is mediated by biological photo-acceptor molecules that are found in a variety of cellular components throughout the human body.
Two cellular components in particular that have been identified are cytochrome c oxidase, which is part of the electron transport chain of mitochondria, and porphyrins, which are found in the eukaryotic cell membrane.
Cytochrome c oxidase is a multi-component membrane protein, which contains a binuclear copper center (CuA) and a heme binuclear center (a3-CuB). Cytochrome c oxidase facilitates the transfer of electrons from cytochrome c to oxygen, driving oxidative phosphorylation.59,60 Researchers believe low-level laser stimulation of cytochrome c oxidase accelerates the transfer rate of electrons and makes more electrons available for the reduction of dioxygen.61-69 Functional changes in the terminal enzyme increase the membrane potential and proton gradient, changing mitochondrial optical properties and increasing the rate of ADP/ATP exchange.70,71
The combination of upregulation of ATP and upregulation of reactive oxygen species directly affect secondary reactions that regulate gene expression, protein and growth factor synthesis, cell proliferation, and many other cellular properties. Upregulation of ATP is coupled to the production of reactive oxygen species, which can affect the intracellular redox state. Sensitization of primary afferent nociceptors is aggravated by TNF-α and other pro-inflammatory cytokines.72 Synthesis of pro-inflammatory cytokines such as TNF-α occurs via the inducible enzyme COX-2, which catalyzes the formation of prostaglandin H2 from arachidonic acid.68 Both prostaglandin E2 (PGE2) and prostacyclin promote pain by stimulating the pain-producing mechanism of bradykinin and other autacoids.71-73
Several classes of non-opioid analgesics act as specific inhibitors of COX-2 and prevent eicosanoid formation.74-78 In vitro and in vivo studies have shown that laser therapy reduces PGE2, interleukin-1α and TNF-α by inhibiting COX-2.55-57 One hypothesis is that laser therapy influences the intracellular redox state by modulating the transcription factor nuclear factor kappa B, which undergoes phosphorylation and ubiquitination, and promotes proteolytic degradation of IKB-a under oxidative stress. A shift in the intracellular redox state may affect the cascade responsible for regulating COX-2 expression, thereby suppressing the synthesis of pro-inflammatory cytokines.
Researchers have shown that low-level laser therapy upregulates VEGF, which promotes neovascularization.54 Enhanced microcirculation may contribute to the stabilization of cell metabolism by increasing cellular nutrient and oxygen concentrations.
What One Small Study Reveals About LLLT For patients With Small Fiber Neuropathy
Although histological evidence of the effectiveness of low-level laser therapy is rather extensive, clinical evidence with well-defined laser parameters is inconsistent. Therefore, we developed a study to assess the efficacy of low-level laser therapy at 635nm with an output intensity of 17.5 mW to promote small fiber nerve regeneration and reduce the symptoms associated with small fiber neuropathy. Recent reports have validated skin biopsy as an accurate method for quantitative assessment of intraepidermal nerve fiber density.57,79 Accordingly, we obtained skin biopsies before and after treatment with low-level laser therapy in order to document nerve regeneration in regions presenting with skin denervation.
Eleven patients diagnosed with small fiber neuropathy via epidermal nerve fiber density testing underwent 12 low-level laser therapy treatments (10 minutes per extremity) three times a week for four weeks. Study participants received treatment from a multiple-diode low-level laser scanning device that emits divergent 635-nm laser light from each diode, generating 17.5mW of output intensity the Erchonia® ML Scanner.
Study authors directed the diodes at the common peroneal nerve at the fibular neck, the posterior tibial nerve at the medial ankle, the deep peroneal nerve at the dorsum of the foot, the superficial peroneal nerve at the anterolateral ankle and the plantar aspect of the foot. The treatment protocol included epidermal nerve fiber density testing before and after laser treatment. (neck of the calf, inner ankle, bottom of foot, outer ankle.)
In addition, we utilized the Total Neuropathy Score-reduced (TNSr) to objectively evaluate each patient’s response to laser therapy. The Total Neuropathy Score-reduced is a combination of subjective questions and physical examination results, and gives a score ranging from 0 to 44 with a higher score representing worse neuropathic pain (see "Measuring Patient Response To Laser Therapy With The Total Neuropathy Score-Reduced"). We quantified both the percent increase in epidermal nerve fiber density in the foot and the leg, and the change in the TNSr. In addition, we asked patients to quantify their overall improvement in neuropathic pain as a percent improvement. (See the table “How Patients Were Asked To Quantify Their Improvement In Neuropathic Pain.”)
The average Total Neuropathy Score (TNS) for patients at baseline was 22.83 with a range between 17 to 26. In comparison to baseline, the average post-treatment TNS exhibited a significant decrease of 8.91 points or 40.05 percent with a range between 24.00 and 70.59 percent. (See the table “Comparison of Total Neuropathy Scores Between Baseline And Post-Treatment Assessment.”)
Assessment of epidermal nerve fiber density of the legs showed a change in the average epidermal nerve fiber density of 0.595 points or 33.15 percent between baseline and post-treatment evaluation points (see the table “Comparison Of Baseline And Post-Treatment Epidermal Nerve Fiber Density Of The Legs”). The average change observed between baseline and post-treatment epidermal nerve fiber density testing was not statistically significant. However, seven of the 11 patients demonstrated an increase in epidermal nerve fiber density of the legs from baseline with a range in percent improvement between 2.15 percent and 1578 percent.
Assessment of epidermal nerve fiber density of the feet showed an average change between baseline and post-treatment evaluation periods of 0.648 points or 56.54 percent. This change was not statistically significant. However, a majority of participants (6 of 11) revealed an improvement in epidermal nerve fiber density of the feet with a range between 32.44 percent and 220 percent. (See the table “Comparison of Baseline And Post-Treatment Epidermal Nerve Fiber Density Scores Of The Feet.”)
We have included figures showing actual histological specimens of a 65-year-old study patient before and after laser therapy. As one can see in figures a and c, at the start of the study, the patient has very few small fiber nerves that cross the basement membrane into the epidermis. The epidermal nerve fiber density before laser therapy for this patient was significantly less than the normal range, resulting in a diagnosis of small fiber neuropathy. In figures b and d, after laser therapy, there has been a significant increase in the number of small fibers penetrating into the epidermis and the calculated epidermal nerve fiber density increased to the normal range.
For each participant in the study, we reported an improvement in the overall perceived pain rating. Study participants exhibited an average improvement in neuropathic pain of 75 percent.
The data acquired from this prospective, non-randomized, non-controlled study demonstrates the potential utility of low-level laser therapy. These data show a clinically meaningful outcome for the treatment of neuropathic pain without an adverse event. However, a placebo-controlled, randomized, double-blind, multi-centered clinical investigation is warranted in order to elucidate the complete efficacy of this therapeutic approach. Furthermore, it would be important to enroll study participants who demonstrate similar baseline epidermal nerve fiber density of the legs and feet in order to appropriately quantify any improvement produced by low-level laser therapy.