Shawn Hanlon Therapeutic Modalities Dr. Sterner 12/2/10 The Effects of Low-level Laser Therapy on Wound Healing: A Literature Review Introduction The use of Low-Level Laser Therapy (LLLT) has grown in popularity by allied health professionals over the past forty years for the management of acute and chronic wounds. Multiple studies have been conducted to examine the effects, parameters, and indications for laser therapy. No matter what aspect of laser therapy is assessed in study, the cumulative finding in the effects of LLLT is its positive effect on wound healing.1-5, 7-10 The physiological effects of LLLT are majorly dependent on the energy density dosage, measured in J/cm2 or W/cm2 and treatment time of irradiance, measured in seconds. The term Low level laser is a reference to the optical energy of the laser beam, it is considered a low intensity or “cold” laser. There is no heating effect with low power lasers and thereby can cause no thermal changes to the tissue.5 Studies have used a multitude of substrates to create the lasers for LLLT, the most popular being helium neon (HeNe) and Gallium Arsenide (GaAs). The active medium used to produce the laser will determine the maximum depth of penetration for energy absorption in the tissues. HeNe lasers are commonly used for superficial wounds (burns, abrasions) with an estimated 13mm. GaAs lasers are commonly used for subcutaneous stimulation (ligaments, muscles, periosteum) with depths up to 5cm.5, 10 The objective of this review is to investigate the efficacy of LLLT for the management of chronic pathologies including achilles tendinopathy and knee osteoarthritis. Also, this will assess the effects of LLLT on superficial wounds including third degree burns, ulcers, and abrasions. In addition, this review will examine the studies on the effects of LLLT on the healing process at the cellular level, specifically mast cell activity and prostaglandin E2 concentration. Chronic Pathologies A chronic injury are most often caused by inflammation that does not reside or due to a number of physiological reasons such as edema formation, reinjury, poor vascularization, or fibrotic development. Injuries that are classified chronic have lasted more than 10 days or are brought on from overuse and have ceased to heal or are frequently reinjured, impeding the healing process. Laser therapy has been promoted for its positive effects in enhancing cell function, analgesia, improved blood flow and expedited tissue repair. 2,4, 6 Tendinitis Tendinitis or tendinopathy is a musculoskeletal inflammatory disorder. All common treatments for tendinitis offer only a short term relief of symptoms. Given the optimal parameters, LLLT can be used for long term relief of inflammation and pain. A study was performed on LLLT and the effects on the treatment of achilles tendinitis and peritendinous prostaglandin E2 concentrations. Subjects were instructed to aggravate their tendinopathy symptoms through physical activity. Immediately after activity, infrared LLLT was used with a wavelength of 904nm, a dosage of 5.4 J per point and an energy density of 20mW/cm2 by a GaAs laser on the experimental group and the control group received a placebo treatment. After treatment, pain threshold showed significant improvement at 70, 90 and 105 mins post-exercise. Prostaglandin E2 concentration showed a gradual decrease over the 105 mins post-treatment, surpassing baseline measurements. The experimental group showed less of a decrease than the control group in a single hop test. Ultrasound Doppler showed that there were no significant changes in peritendinous or intratendinous blood flow when compared to the control group however given the timing of when this measurement was taken; enough time had lapsed for the body to reduce swelling due to rest. This study demonstrates that LLLT can reduce inflammation as displayed by a measured decrease in Prostaglandin E2 concentration in Achilles tendinitis. In addition, LLLT showed an effect in improving pain tolerance by point tenderness and a single hop test.2 Osteoarthritis Laser therapy is thought to have a large impact on microcirculation of an injured area.7 Due to osteoarthritis, articular degeneration has shown to reduce circulation to the joint and subsequently inhibit proliferation of the damaged tissue. LLLT has been praised by numerous authors to have an analgesic effect and changes in microcirculation.5, 6 A double blind study by Hegedus et. al. looked at 27 men and women with mild to moderate knee osteoarthritis to determine the pain relieving effects and microcirculation changes in the knee as a result of LLLT. The experimental group was treated with a GaAlAs diode laser twice a day for 4 weeks. The parameters chosen were power 50mW, and a wavelength of 830nm at a dosage of 6J per point. The treatment time was not stated. The placebo group received a power intensity of .5mW. The diode laser was directed at 3 areas (the femoral epicondyle, joint line, and tibial condyle) on the medial and lateral aspect of the knee, the biceps femoris tendon, and the semitendinosis tendon. Joint flexion was assessed immediately after treatment showing an increase from 105˚ baseline to 122˚. The placebo group showed no significant change in joint flexion. The experimental group showed significant reduction in pressure sensitivity compared to before treatment and continued to lower through treatment. Most remarkably during the treatment period, thermograms showed an increase in temperature in previously cold areas as well as a spreading of the heated area, thus confirming the increase in microcirculation in the treated area. The placebo group showed no changes in temperature. For this study, the positive effects of pain relief, pressure sensitivity, and joint flexion lasted up to 2 months after treatment ceased. 6 Superficial Wounds Laser therapy is becoming increasingly beneficial in the treatment of superficial wounds. Evidence has shown the LLLT with optimal parameters can increase the rate of tissue healing, wound contraction rate, and altogether expedite the healing phases. 3, 4, 7-9 So far in literature, laser therapy has been used to assess third degree burns on rats, abrasions and turf burns on humans, and ulcerations on humans.1, 3, 7, 8 Most studies have found positive effects however there is much to investigate and still to prove in regards to optimal treatment parameters. Third Degree Burns Burns are not only a debilitating risk, they also provide a breeding ground for infectious disease. It is the intent of laser therapy to accelerate the healing of third degree burns and reduce the risk of infection. A study by Ezzati, et. al. investigated the outcomes of pulsed LLLT on third degree burns. 74 rats were burned in 2 locations (on the distal and proximal back) and then placed in 4 groups. The burned skin measured 3.8cm2. Group 1 received LLLT with the laser switched off; group 2 and 3 treated the distal wound with a 3,000 Hz-pulsed infrared laser with a power output of 70 Watts. Group 4 treated the distal burn with a topical burn cream. All groups used the proximal burn as the control group. LLLT was used immediately after the burns were incurred. Groups 2 and 3 were given treatment for 62 and 310 seconds, respectively, for 3 times per week. For both groups 2 and 3, the treatment area was made into eight 1cm2 squares using the burn as the focal point, the laser probe was held perpendicularly to each square for their respective treatment time. For the first 7 days the treatment time was calculated with energy densities of 1J/cm2 for group 2 and 5J/cm2 for group 3, using a pulse duration of 180µsec throughout the entire treatment series. After day 7 the treatment times were reduced by a third of the original time. On days 7 and 15 the researchers took a culture swab testing for various strains of staphylococcus, Bacillus subtilis, and other bacterial skin diseases and also took photographs to show would size. At the end of the 4 week study, the presence of staphylococcus was significantly lower in groups 2 and 3 compared to the other groups and their respective proximal burns. Group 3 with a energy density of 11.7 J/cm2 showed the greatest reduction in wound size and therefore the fastest wound closure rate. The lower energy density was only effective in the early stages of healing. LLLT also demonstrates to be more effective than topical burn ointment used in group 4. Furthermore, this study provides evidence of LLLT inhibiting the development of bacterial infection. Ulcerations LLLT is becoming a common modality promote healing of ulcer wounds on the foot, ankle and lower leg. A clinical study was developed to evaluate the efficacy of LLLT on patients suffering from leprosy sequelae. Leprosy is commonly associated with neuropathic ulcers; 30% of individuals with leprosy develop peripheral nerve damage.1 An experimental group of 25 out of 51 subjects with ulcers were treated with LLLT 3 times per week for 12 weeks while the control group was treated with wound cleaning creams. This study used a TWIN LASER, the semiconductor laser was an indium-gallium-alluminum-phosphide. Using a continuous radiation emission of visible red light with a wavelength of 660nm and a spot area of .04 cm2, the researchers chose an energy density of 4 Joules per point in the wound edges and 2J/cm2 in the wound bed. The power density chosen was 1W/cm2. The wound beds were treated with a scanning technique having no direct skin contact. The laser probe was held 1 cm away from the skin. The edges of the ulcer were treated with a spot number technique, irradiating the wound edges at points spaced 1 cm apart. A contact technique was used with a transparent piece of polyvinyl chloride attached to the laser probe to prevent direct contact, this was then applied every 1cm around the wound border. Ulcer area, depth and pressure ulcer scale for healing tool score (PUSH) were taken before and after the experiment. Area was determined by photograph. The skin lesions in this study varied from blisters to fissures fibrotic skin development with varying ulcer area and depth, however there was no evidence of increased wound healing when compared to the control group. A special consideration is the control of patients with high blood pressure, as comorbidity has been shown to negatively affect wound healing with leprosy patients. Also, during treatments the patients with plantar ulcers wore no adaptive footwear and made no attempts to reduce the repetitive pressure loading on the ulcers. 8 Abrasions It has been reported in studies over the past decade that LLLT has many benefits in wound healing for abrasions, ulcers, incisions, burns and other various acute wounds. 1, 3, 4, 7, 8 Hopkins et. al. assessed the benefits of tissue healing and pain relief as a result of laser therapy to clarify the various results and conclusions of previous studies.7 In this study, two abrasions were made on a human forearm by 60 grit sand paper each measuring 6.25cm in diameter. One wound would receive laser therapy and the other would receive a sham treatment. Wounds were treated with a 46-diode cluster head laser (surface area of 19.6cm2) the average power density was 8 J/cm2 for a treatment time of 2 minutes, 5 seconds at a 700Hz pulse rate. Subjects returned daily for a total of 20 days for a photograph, treatment, and overall assessment. Healing was measured by wound contraction via the photographs, and the change in chromatic red and luminance. Chromatic red is an indicator of wound healing as a wound heals it changes from dark red to pale pink. Luminance is a reference to the homogeneity of the wound as it heals and becomes more smooth in texture and consistent in appearance.8 Throughout the evaluation, the laser group had greater wound contraction than the sham group. The most significant difference was noted on day 6 where the laser group displayed 153% greater wound contraction than the sham group. Cellular Response A proposed mechanism for how low power laser therapy enhances the healing process is light energy absorbed by mitochondria, which increases cellular energy and stimulates the release of chemical mediators such as fibroblasts and endothelial cells.3 Evidence has shown an increase in fibroblast activity, changed in collagen sensitivity, Mast cell granulation, and prostaglandin E2 concentrations in patients treated with LLLT with appropriate parameters. Mast Cells Granulation tissue is mainly controlled by growth factors released by mast cells and macrophages. Mast cells play an important role in collagen formation, vascular permeability and angiogenisis.8 Through LLLT, mast cells can be stimulated to release growth factors and other substrates that aide in the proliferation stage of healing.3 A study by Bayat et. al. on the effects of LLLT on mast cell numbers was performed by testing mast cell counts in third degree burns.9 65 rats were taken and divided into 5 groups, the control group received no treatment for their burns. Two laser groups were treated with 38.2 J/cm2 or 76.4 J/cm2 respectively. Each treatment used a 10mW HeNe laser at a wavelength of 632.8µm, a continuous frequency, and a spot area of 3.14mm2. Group 1 using 38.2J/cm2 received treatment for 120 seconds and Group 2 receiving 76.4 J/cm2 received treatment for 240 seconds. Rats in the fourth group were treated with a topical burn ointment. The fifth group was not burned and used as a “normal” group. Each variable group received treatment on day 1 after burning and once daily until the experiment was completed. Mast cell count was assessed through samples excised from the burned skin on day 7 (inflammatory phase), day 16 (proliferation phase), and day 30 (maturation phase). Like other studies, the laser groups showed the most significant differences in mast cells occurred during the inflammatory phase of healing. Group 1 using the lower treatment time and energy density was significantly higher than the higher energy density treatment group. At day 16, the topical burn ointment group showed the highest amount of mast cells; however, there was no significant difference in any group. At the final assessment on day 30, there was no significant difference in mast cells in any of the groups. When treating third degree burns, this evidence shows that during the inflammatory phase, using LLLT with an energy density of 38.2 J/cm2 showed the greatest increase in type 1 and type 2 mast cells. Conclusion In the majority of studies, the effects of LLLT were the highest when compared to control during the inflammatory phase of healing. The outcome of treatment by low lever laser therapy is dependent on dosage of energy density. When choosing a specific medium for laser therapy, it has been determined that HeNe lasers penetrate superficially, having great benefits on healing superficial soft tissue wounds. GaAs lasers are beneficial for the management of active tendinitis, ligament and possibly bone healing. When considering dosage and parameters for LLLT, it is helpful to remember the Arndt-Schulz law, “weak stimuli excite physiological activity, moderately strong favour it, strong ones retard it and very strong ones arrest it.” 5 Much research is still needed in regards to optimal parameters for the treatment of all pathologies indicated for laser therapy. To better understand how to utilize LLLT, clinical studies must focus on reporting parameters including wavelength, energy dosage, and form of laser substrate as well as provide the rationale for choosing each combination. Low power lasers have found a niche in a clinical setting for treatment of acute injuries in the early inflammatory stages of healing and also for superficial wounds and for the management of chronic inflammatory pathologies, and what has been proven by the positive effects of LLLT will provide a path to new research on different technologies, yielding even better results. References 1. Barreto J, Salgado C. Clinic-epidemiological evaluation of ulcers in patients with leprosy sequelae and the effect of low level laser therapy on wound healing: a randomized clinical trial. BMC Infectious Diseases. 2010; 10:237. 2. Bjordal JM, Lopes-Martin RAB, Iverson VV. A randomized, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. J Sports Med. 2006; 40:76-80. 3. Ezzati A, Bayat M, Taheri S, Mohsenifar Z. Low-level laser therapy with pulsed infrared laser accelerates third degree burn healing process in rats. Journal of rehabilitation Research and Development. 2009; 46:543-54. 4. Saltmarche A. Low level laser therapy for healing acute and chronic wounds- the Extendicare experience. Int Wound J. 2008; 5:351-360. 5. Thiel H. Low power laser therapy- an introduction and a review of some biological effects. The Journal of the CCA. 1986; 30: 133-37. 6. Hegedus B, Viharos L, Gervain M, Galfi M. The effect of low-level laser in knee osteoarthritis: A double blind, randomized, placebo controlled trial. Photomedicine and Laser Surgery. 2009; 27: 577-84. 8. Hopkins J, McLoda T, Seegmiller J, Baxter G. Low-level laser therapy facilities superficial wound healing in humans: A triple blind, sham controlled study. Journal of Athletic Training. 2004; 39(3): 223-229. 9. Bayat M, Vasheghani M, Razavie N, Reza M. Effects of low-level laser therapy on mast cell number and degranulation in third degree burns. Journal of rehabilitation Research and Development.2008; 45: 931-38. 10. Posten W, Wrone D, Dover J, Arndt K, Silapunt S, Alam A. Low-level laser therapy for wound healing: Mechanism and efficacy. Dermatol Surg. 2005; 31: 334-340.