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

   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.74-78In 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.

   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.”)

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