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LE Magazine October 2008

Laser Treatment

Laser acupuncture: past, present, and future.

Laser acupuncture is defined as the stimulation of traditional acupuncture points with low-intensity, nonthermal laser irradiation. Although the therapeutic use of laser acupuncture is rapidly gaining in popularity, objective evaluation of its efficacy in published studies is difficult because treatment parameters such as wavelength, irradiance, and beam profile are seldom fully described. The depth of laser energy transmission, likely an important determinant of efficacy, is governed not only by these parameters, but also by skin properties such as thickness, age, and pigmentation-factors which have also received little consideration in laser acupuncture. Despite the frequently equivocal nature of the published laser studies, recent evidence of visual cortex activation by laser acupuncture of foot points, together with the known ability of laser irradiation to induce cellular effects at subthermal thresholds, provides impetus for further research.

Lasers Med Sci. 2004;19(2):69-80

Low level laser therapy for nonspecific low-back pain.

BACKGROUND: Low-back pain (LBP) is a major health problem and a major cause of medical expenses and disablement. Low level laser therapy (LLLT) can be used to treat musculoskeletal disorders such as back pain. OBJECTIVES: To assess the effects of LLLT in patients with non-specific LBP. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2005, Issue 2), MEDLINE, CINAHL, EMBASE, AMED and PEDro from their start to November 2007 with no language restrictions. We screened references in the included studies and in reviews and conducted citation tracking of identified RCTs and reviews using Science Citation Index. We also contacted content experts. SELECTION CRITERIA: Randomised controlled clinical trials (RCTs) investigating LLLT to treat non-specific low-back pain were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed methodological quality using the criteria recommended by the Cochrane Back Review Group and extracted data. Studies were qualitatively and quantitatively analysed according to Cochrane Back Review Group guideline. MAIN RESULTS: Seven heterogeneous English language RCTs with reasonable quality were included.Three small studies (168 people) separately showed statistically significant but clinically unimportant pain relief for LLLT versus sham therapy for sub-acute and chronic low-back pain at short-term and intermediate-term follow-up (up to six months). One study (56 people) showed that LLLT was more effective than sham at reducing disability in the short term. Three studies (102 people) reported that LLLT plus exercise were not better than exercise, with or without sham in the short-term in reducing pain or disability. Two studies (90 people) reported that LLLT was not more effective than exercise, with or without sham in reducing pain or disability in the short term. Two small trials (151 people) independently found that the relapse rate in the LLLT group was significantly lower than in the control group at the six-month follow-up. No side effects were reported. AUTHORS’ CONCLUSIONS: Based on the heterogeneity of the populations, interventions and comparison groups, we conclude that there are insufficient data to draw firm conclusions on the clinical effect of LLLT for low-back pain. There is a need for further methodologically rigorous RCTs to evaluate the effects of LLLT compared to other treatments, different lengths of treatment, wavelengths and dosages.

Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005107

A systematic review with procedural assessments and meta-analysis of low level laser therapy in lateral elbow tendinopathy (tennis elbow).

BACKGROUND: Recent reviews have indicated that low level level laser therapy (LLLT) is ineffective in lateral elbow tendinopathy (LET) without assessing validity of treatment procedures and doses or the influence of prior steroid injections. METHODS: Systematic review with meta-analysis, with primary outcome measures of pain relief and/or global improvement and subgroup analyses of methodological quality, wavelengths and treatment procedures. RESULTS: 18 randomised placebo-controlled trials (RCTs) were identified with 13 RCTs (730 patients) meeting the criteria for meta-analysis. 12 RCTs satisfied half or more of the methodological criteria. Publication bias was detected by Egger’s graphical test, which showed a negative direction of bias. Ten of the trials included patients with poor prognosis caused by failed steroid injections or other treatment failures, or long symptom duration or severe baseline pain. The weighted mean difference (WMD) for pain relief was 10.2 mm [95% CI: 3.0 to 17.5] and the RR for global improvement was 1.36 [1.16 to 1.60]. Trials which targeted acupuncture points reported negative results, as did trials with wavelengths 820, 830,and 1064 nm. In a subgroup of five trials with 904 nm lasers and one trial with 632 nm wavelength where the lateral elbow tendon insertions were directly irradiated, WMD for pain relief was 17.2 mm [95% CI: 8.5 to 25.9] and 14.0 mm [95% CI: 7.4 to 20.6] respectively, while RR for global pain improvement was only reported for 904 nm at 1.53 [95% CI: 1.28 to 1.83]. LLLT doses in this subgroup ranged between 0.5 and 7.2 Joules. Secondary outcome measures of painfree grip strength, pain pressure threshold, sick leave and follow-up data from 3 to 8 weeks after the end of treatment, showed consistently significant results in favour of the same LLLT subgroup (p < 0.02). No serious side-effects were reported. CONCLUSION: LLLT administered with optimal doses of 904 nm and possibly 632 nm wavelengths directly to the lateral elbow tendon insertions, seem to offer short-term pain relief and less disability in LET, both alone and in conjunction with an exercise regimen. This finding contradicts the conclusions of previous reviews which failed to assess treatment procedures, wavelengths and optimal doses.

BMC Musculoskelet Disord. 2008 May 29;9:75

Evaluation of low-level laser therapy in the treatment of temporomandibular disorders.

OBJECTIVE: The purpose of this study was to assess the effectiveness of low-level laser therapy (LLLT) in the treatment of myogenic originated temporomandibular disorders (TMD). BACKGROUND DATA: Limited studies have demonstrated that LLLT may have a therapeutic effect on the treatment of TMD. METHODS: Thirty-nine patients with myogenic TMD-associated orofacial pain, limited mandibular movements, chewing difficulties, and tender points were included in this study. Twenty-four of them were treated with LLLT for 10 sessions per day excluding weekends as test group, and 15 patients with the same protocol received placebo laser treatment as a control group. These parameters were assessed just before, just after, and 1 month after the treatment. RESULTS: Maximal mouth-opening improvement, and reductions in pain and chewing difficulty were statistically significant in the test group when compared with the control group. Statistically significant improvements were also detected between two groups regarding reduction in the number of tender points. CONCLUSION: Based on the results of this placebo-controlled report, LLLT is an appropriate treatment for TMD and should be considered as an alternative to other methods.

Photomed Laser Surg. 2006 Oct;24(5):637-41

Effect of low level laser therapy in rheumatoid arthritis patients with carpal tunnel syndrome.

OBJECTIVE: the aim of the present study was to evaluate the efficacy of low level laser therapy (LLLT) in patients with rheumatoid arthritis (RA) with carpal tunnel syndrome (CTS). MATERIAL AND METHODS: a total of 19 patients with the diagnosis of CTS in 19 hands were included and randomly assigned to two treatment groups; LLLT (Group 1) (10 hands) with dosage 1.5 J/ per point and placebo laser therapy group (Group 2) (9 hands). A Galium-Aluminum-Arsenide diode laser device was used as a source of low power laser with a power output of 50 mW and wavelength of 780 nm. All treatments were applied once a day on week days for a total period of 10 days. Clinical assessments were performed at baseline, at the end of the treatment and at month 3. Tinel and Phalen signs were tested in all patients. Patients were evaluated for such clinical parameters as functional status scale (FSS), visual analogue scale (VAS), symptom severity scale (SSS) and grip-strength. However, electrophysiological examination was performed on all hands. Results were given with descriptive statistics and confidence intervals between group means at 3 months adjusted for outcome at baseline and for the difference between unadjusted group proportions. RESULTS: clinical and electrophysiological parameters were similar at baseline in both groups. Improvements were significantly more pronounced in the LLLT group than placebo group. A comparison between groups showed significant improvements in pain score and functional status scale score. Group mean differences at 3 months adjusted at baseline were found to be statistically significant for pain score and functional status scale score. The 95% significant confidence intervals were [-15 - (-5)] and [-5 - (-2)] respectively. There were no statistically significant differences in other clinical and electrophysiological parameters between groups at 3 months. CONCLUSIONS: our study results indicate that LLLT and placebo laser therapy seems to be effective for pain and hand function in CTS. We, therefore, suggest that LLLT may be used as a good alternative treatment method in CTS patients with RA.

Swiss Med Wkly. 2007 Jun 16;137(23-24):347-52

Clinical effect of CO(2) laser in reducing pain in orthodontics.

OBJECTIVE: To test the hypothesis that there is no difference in the pain associated with orthodontic force application after the application of local CO(2) laser irradiation to the teeth involved. MATERIALS AND METHODS: Separation modules were placed at the distal contacts of the maxillary first molars in 90 patients in this single-blinded study. In 60 of these patients (42 females and 18 males; mean age = 19.22 years) this was immediately followed by laser therapy. The other 30 patients (18 females and 12 males; mean age = 18.8 years) did not receive active laser irradiation. Patients were then instructed to rate their levels of pain on a visual analog scale over time, and the amount of tooth movement was analyzed. RESULTS: Significant pain reductions were observed with laser treatment from immediately after insertion of separators through day 4, but no differences from the nonirradiated control side were noted thereafter. No significant difference was noted in the amount of tooth movement between the irradiated and nonirradiated group. CONCLUSIONS: The hypothesis was rejected. The results suggest that local CO(2) laser irradiation will reduce pain associated with orthodontic force application without interfering with the tooth movement.

Angle Orthod. 2008 Mar;78(2):299-303

Systematic review of the literature of low-level laser therapy (LLLT) in the management of neck pain.

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) is widely used in the treatment of musculoskeletal pain. However, there is controversy over its true efficacy. We aimed to determine the efficacy of LLLT in the treatment of neck pain through systematically reviewing the literature. STUDY DESIGN/MATERIALS AND METHODS: A search of computerized bibliographic databases covering medicine, physiotherapy, allied health, complementary medicine, and biological sciences was undertaken undertaken from date of inception until February 2004 for randomized controlled trials of LLLT for neck pain. A comprehensive list of search terms was applied and explicit inclusion criteria were developed a priori. Twenty studies were identified, five of which met the inclusion criteria. RESULTS: Significant positive effects were reported in four of five trials in which infrared wavelengths (lambda = 780, 810-830, 904, 1,064 nm) were used. Heterogeneity in outcome measures, results reporting, doses, and laser parameters precluded formal meta-analysis. Effect sizes could be calculated for only two of the studies. CONCLUSIONS: This review provides limited evidence from one RCT for the use of infrared laser for the treatment of acute neck pain (n = 71) and chronic neck pain from four RCTs (n = 202). Larger studies are required to confirm the positive findings and determine the most effective laser parameters, sites and modes of application.

Lasers Surg Med. 2005 Jul;37(1):46-52

Import of radiation phenomena of electrons and therapeutic low-level laser in regard to the mitochondrial energy transfer.

OBJECTIVE: The authors describe a consistent theoretical model of the cellular energy transfer (respiratory chain) by taking into consideration the radiation phenomena of electrons and therapeutic low level laser. SUMMARY BACKGROUND DATA: Biochemical models of the cellular energy transfer regard the classical corpuscular aspect of electrons as the responsible energy carriers, thereby ignoring the wave-particle dualism of the electrons and the import of radiation energy in this process. METHODS: The authors show the influence of radiation phenomena on the cellular energy transfer, explaining consistently some of the intermediate steps of this complex process. RESULTS: Because of the inherent wave-particle dualism of the electrons, it is appropriate to regard radiation phenomena to explain the cellular energy transfer. The classical biochemical models use only the particle part of the electrons as energy carriers. The connection between energy transport by radiation and the order in structures may be understood if, for instance, structurally bound energy is released during the dissolution of structures (oxidation of foodstuffs) or is again manifested (final reduction of oxygen to water). With attention to the energy values relevant for the respiratory chain, the import of electromagnetic radiation of characteristic ranges of wavelengths on the cellular energy transfer becomes evident. Depending on its wavelength, electromagnetic radiation in the form of light can stimulate macromolecules and can initiate conformation changes in proteins or can transfer energy to electrons. Low level laser from the red and the near infrared region corresponds well with the characteristic energy and absorption levels of the relevant components of the respiratory chain. This laser stimulation vitalizes the cell by increasing the mitochondrial ATP(adenosine-tri-phosphate)-production. CONCLUSIONS: With regard to radiation phenomena and its enhanced electron flow in the cellular energy transfer (respiratory chain), it is possible to explain the experimentally found increase of ATP-production by means of low-level laser light on a cellular level. Intense research for this biostimulative effect is still necessary.

J Clin Laser Med Surg. 1998 Jun;16(3):159-65

Mitochondrial membrane potential after low-power laser irradiation.

We used the lipophilic cationic fluorescent dye 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethyl-benzimidazol-carbocyanine iodide (JC-1) to determine mitochondrial membrane potential (mdeltapsi) in Hep-2 cells after irradiation with low-power laser (lambda=635 nm). Through this methodology it was possible to analyze the variation on mitochondrial number and mdeltapsi, in cells irradiated for 100, 150 and 200 s with energy density of 100 mJ/cm(2). Our results show that JC-1 dye allows the identification of populations with different mitochondria morphology as well as the functionality of this organelle in the cells incubated for 1, 6 and 24 h, after irradiation with low-power laser.

Lasers Med Sci. 2004;18(4):204-6

Low level laser irradiation stimulates mitochondrial membrane potential and disperses subnuclear promyelocytic leukemia protein.

BACKGROUND AND OBJECTIVES: Low level laser irradiation (LLLI) is used to promote wound healing. Molecularly it is known to stimulate mitochondrial membrane potential (MMP), cytokine secretion, and cell proliferation. This study was designed to determine the influence of LLLI on the kinetics of MMP stimulation and decay, specific cytokine gene expression, and subcellular localization of promyelocytic leukemia (PML) protein on HaCaT human keratinocytes. STUDY DESIGN/MATERIAL AND METHODS: The cells were irradiated by a 780 nm titanium-sapphire (Ti-Sa) laser with 2 J/cm(2) energy density. MMP was monitored with Mitotracker, a mitochondrial voltage-sensitive fluorescent dye. Cytokine gene expression was carried out using semi-quantitative-reverse transcription polymerase chain reaction. Subcellular localization of PML protein, a cell-cycle checkpoint protein, was determined using immunofluorescent staining. RESULTS: The fluorescence intensity of MMP was increased immediately after the end of LLLI by 148 +/- 6% over control (P<0.001). Subsequently it decayed, reaching 51 +/- 14% of the control level (P < 0.01) within 200 minutes. This decay was characterized by an exponential curve (R = 0.96) with a lifetime of 79 +/- 36 minutes (P < 0.05). Following irradiation, the expression of interleukin-1alpha, interleukin-6, and keratinocyte growth factor (KGF) genes were transiently upregulated; but the expression of the proinflammatory gene interleukin-1beta, was suppressed. The subnuclear distribution of PML was altered from discrete domains to its dispersed form within less than 1 hour after LLLI. CONCLUSIONS: These changes reflect a biostimulative boost that causes a shift of the cell from a quiescent to an activated stage in the cell cycle heralding proliferation and suppression of inflammation. Further characterization of MMP kinetics may provide a quantitative basis for assessment of the effect of LLLI in the clinical setting.

Lasers Surg Med. 2004;35(5):369-76

Cellular effects of low power laser therapy can be mediated by nitric oxide.

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the possibility of involvement of nitric oxide (NO) into the irradiation-induced increase of cell attachment. These experiments were performed with a view to exploring the cellular mechanisms of low-power laser therapy. STUDY DESIGN/MATERIALS AND METHODS: A suspension of HeLa cells was irradiated with a monochromatic visible-to-near infrared radiation (600-860 nm, 52 J/m2) or with a diode laser (820 nm, 8-120 J/m2) and the number of cells attached to a glass matrix was counted after 30 minute incubation at 37 degrees C. The NO donors sodium nitroprusside (SNP), glyceryl trinitrate (GTN), or sodium nitrite (NaNO2) in the concentration range 5 x 10(-9)-5 x 10(-4)M were added to the cellular suspension before or after irradiation. The action spectra and the concentration and fluence dependencies obtained were compared and analyzed. RESULTS: The well-structured action spectrum for the increase of the adhesion of the cells, with maxima at 619, 657, 675, 740, 760, and 820 nm, points to the existence of a photoacceptor responsible for the enhancement of this property (supposedly cytochrome c oxidase, the terminal respiratory chain enzyme), as well as signaling pathways between the cell mitochondria, plasma membrane, and nucleus. Treating the cellular suspension with SNP (5 x 10(-5)M) before irradiation significantly modifies the action spectrum for the enhancement of the cell attachment property (band maxima at 642, 685, 700, 742, 842, and 856 nm). The action of SNP, GTN, and NaNO2 added before or after irradiation depends on their concentration and radiation fluence. CONCLUSIONS: The NO donors added to the cellular suspension before irradiation eliminate the radiation-induced increase in the number of cells attached to the glass matrix, supposedly by way of binding NO to cytochrome c oxidase. NO added to the suspension after irradiation can also inhibit the light-induced signal downstream. Both effects of NO depend on the concentration of the NO donors added. These results indicate that NO can control the irradiation-activated reactions that increase the attachment of cells.

Lasers Surg Med. 2005 Apr;36(4):307-14

Increased expression of mitochondrial benzodiazepine receptors following low-level light treatment facilitates enhanced protoporphyrin IX production in glioma-derived cells in vitro.

BACKGROUND AND OBJECTIVES: This study investigates whether low-level light treatment (LLLT) can enhance the expression of peripheral-type mitochondrial benzodiazepine receptors (PBRs) on glioma-derived tumor cells, and by doing so promote the synthesis of protoporphyrin IX (PpIX) and increase the photodynamic therapy (PDT)-induced cell kill using 5-aminolevulinic acid (ALA). The endogenous photosensitizer, PpIX and related metabolites including coproporphyrin III are known to traffic into or out of the mitochondria via the PBRs situated on the outer mitochondrial membrane. Cells of astrocytic derivation within the brain express PBRs, while neurons express the central-type of benzodiazepine receptor. STUDY DESIGN: Astrocytoma-derived CNS-1 cells were exposed to a range of differing low-level light protocols immediately prior to PDT. LLLT involved using broad-spectrum red light of 600-800 nm or monochromatic laser light specific to 635 or 905 nm wavelength. Cells (5 x 10(5)) were exposed to a range of LLLT doses (0, 1, or 5 J/cm(2)) using a fixed intensity of 10 mW/cm(2) and subsequently harvested for cell viability, immunofluorescence, or Western blot analysis of PBR expression. The amount of PpIX within the cells was determined using chemical extraction techniques. RESULTS: Results confirm the induction of PBR following LLLT is dependent on the dose and wavelength of light used. Broad-spectrum red light provided the greatest cell kill following PDT, although LLLT with 635 nm or 905 nm also increased cell kill as compared to PDT alone. All LLLT regimens increased PBR expression compared to controls with corresponding increases in PpIX production. CONCLUSIONS: These data suggest that by selectively increasing PBR expression in tumor cells, LLLT facilitates enhanced tumor cell kill using ALA-PDT. This may further improve the selectivity and efficacy of PDT treatment of brain tumors.

Lasers Surg Med. 2007 Sep;39(8):678-84

830 nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of 830 nm laser.

We report the formation of 830 nm (cw) laser-induced, reversible axonal varicosities, using immunostaining with beta-tubulin, in small and medium diameter, TRPV-1 positive, cultured rat DRG neurons. Laser also induced a progressive and statistically significant decrease (p<0.005) in MMP in mitochondria in and between static axonal varicosities. In cell bodies of the neuron, the decrease in MMP was also statistically significant (p<0.05), but the decrease occurred more slowly. Importantly we also report for the first time that 830 nm (cw) laser blocked fast axonal flow, imaged in real time using confocal laser microscopy and JC-1 as mitotracker. Control neurons in parallel cultures remained unaffected with no varicosity formation and no change in MMP. Mitochondrial movement was continuous and measured along the axons at a rate of 0.8 microm/s (range 0.5-2 microm/s), consistent with fast axonal flow. Photoacceptors in the mitochondrial membrane absorb laser and mediate the transduction of laser energy into electrochemical changes, initiating a secondary cascade of intracellular events. In neurons, this results in a decrease in MMP with a concurrent decrease in available ATP required for nerve function, including maintenance of microtubules and molecular motors, dyneins and kinesins, responsible for fast axonal flow. Laser-induced neural blockade is a consequence of such changes and provide a mechanism for a neural basis of laser-induced pain relief. The repeated application of laser in a clinical setting modulates nociception and reduces pain. The application of laser therapy for chronic pain may provide a non-drug alternative for the management of chronic pain.

J Peripher Nerv Syst. 2007 Mar;12(1):28-39

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