Therapeutic Lasers in Postoperative Healing Wendy Baltzer, DVM, PhD, DACVS Oregon State University College of Veterinary Medicine

Introduction The term laser stands for light amplification stimulated by emission of radiation. The energy emitted from a laser has a fixed wavelength and is very coherent, that is, each photon emitted is in the same phase. This makes laser light different from the light emitted by a light bulb, for example, and the energy produced can be collimated to cut tissue as with surgical lasers or the beam can be made wide enough to not cut but warm the tissues, as with therapeutic lasers.1 There are several types of therapeutic lasers including defocused CO2, defocused Ruby, HeNe, InGaAIP, GaAIA, and GaA. Each has a different mechanism of energy storage and wavelength of laser light emitted. The most commonly used veterinary therapeutic laser is the GaAIA, or Galliumaluminium-arsenide laser. The wavelength used is 800-830 nm which is invisible, however, most units have a visible light in the probe to visualize what tissue is undergoing biostimulation.1 Safety All lasers have classification for safety, including their ability to cause retinal damage. Lasers capable of damaging the eye have a parallel light beam of small diameter and have higher (increased wattage) power settings. Radiation from the laser above 1400 nm is absorbed by the lens and above 2500 nm is absorbed by the cornea, and therefore does not reach the retina. Lasers in the visible light range such as laser pointers cause a blink reflex thus also preventing a long exposure time to the eye, whereas lasers in the invisible light range are inherently more dangerous. Laser pointers are also far too low powered to cause eye damage. Five classes of lasers have been established with classes 1-3A considered safe for eyes while 3B carries some risk of eye injury and class 4 definitely causes eye injury. Class 4 lasers are used in manufacturing, surgical cutting and now in therapeutic biostimulation. Class 4 lasers produce light in the 800-1400 nm range which focus on the retina and therefore cause damage there.1 Hair and pigmented skin absorb more of the radiation from the laser and therefore using the laser in these areas can cause burned hair or skin, especially if the laser is left focused on one area for an increased amount of time, such as more than one second. Why use a class 4 laser for therapeutic applications when you certainly do not what to cut the tissue? For better penetration to deeper tissues. With a 60 to 100-mWatt class 4 laser, you can treat tissues 2 to 3 cm deep to the surface of the skin. This allows for treatment of acryl lick granulomas to coxofemoral osteoarthritis.2 Mechanism of Action The primary mechanism of lasers is through the interaction of photons with cells, proteins, cell membranes and DNA/RNA. Porphyrins react with polarized light generated in the tissue from the laser and the cytochromes in mitochondria react to form ATP as well as reactive oxygen species. By changing the Redox state of the cell to oxidation, more ATP is generated and the pH of the cell increases.3,4 In addition, heat is generated in areas where polarized light is generated, causing changes in microcirculation and Na+ and K+ gradients.5,6 Finally, the laser creates an environment that favors cellular repair.7 This may be due to changing the charge or electrical gradient of cellular membranes and making them more permeable. The secondary mechanism of action is the resulting cellular and tissue responses following interaction with photons and polarized light. Cellular production of DNA and RNA synthesis increases as well as

ATP, and up to 110 genes are regulated by laser irradiation.8 Most of these genetic effects work to increase cell proliferation and decrease apoptosis. Both the p38 mitogen activated protein kinase signaling pathway and platelet derived growth factor signaling pathway are upregulated by therapeutic (low level) laser therapy. In addition, tissues are in various stages of electrical stimulation are capable of acting as a laser themselves, that is they can generate a photon as the laser photon hits the cell and thus produce deeper tissue biostimulation than the original photon from the laser itself is capable of producing. It is important to note that 10% of animals and humans are resistant to laser therapy. Uses of Therapeutic Lasers GaAiA lasers can inhibit pain sensation by blocking c-fiber transmission in damaged tissue.9 Lasers also increase nitric oxide locally, which also inhibits pain sensation.1 The temperature of tissue is increased by laser therapy and is due in part to an increase in blood flow.1,10 Temperatures rise 0.4-1C in the tissues for up to 30 minutes following cessation of laser therapy.11,12 Lasers also stimulate immunity by activating lymphocytes, mast cells and macrophages in tissue and whole blood so that even wounds in another part of the body that was not treated respond with faster healing times.13 14 Healing is also stimulated by an increase in procollagen synthesis by fibroblasts and cellular replication of endothelial cells and keratinocytes. By increasing cell membrane permeability, there is an increase in seratonin and superoxide dismutase levels which accelerates the inflammatory process. This can be beneficial or detrimental and somewhat controlled by the duration, timing and wavelength of low level laser therapy used. Horses are more sensitive to the effects of laser therapy and the laser can be used to identify areas of pain/inflammation. Horses are also more sensitive to pulsed frequency laser therapy and slower pulses, lower frequencies may be necessary. In addition, laser therapy may make a lame horse sound but that is through alleviation of pain and the primary injury still exists, therefore do not allow the horse to work until the injury has resolved. Defocused CO2 laser therapy has been used successfully in acute traumatic synovitis in horses.15 Both horses and dogs have coats that can be impenetrable to light, and while you can part the hair and work in areas, I require my small animal patients have the area clipped and free of hair. Laser therapy has been used successfully by veterinarians for acral lick dermatitis, chronic degenerative joint and disk disease, wounds- surgical or septic, tendon, ligament and muscle injuries (although laser therapy has not been proven effective in horses with tendonitis), inflammation and edema from blunt trauma, and even epilepsy in dogs. Do not use a laser that has a pulsed visible light on epileptics as this may cause a seizure.1 Current investigations into the use of low level laser therapy include bone and meniscal healing, and wound healing times in blinded, placebo controlled experiments in dogs. Too Much of a Good Thing The thyroid gland should not be irradiated with a therapeutic laser since hypothyroidism can result.16 Treatment of neoplasia with a therapeutic laser is not recommended, nor is treating a patient with a therapeutic laser that has a malignancy distant to the site of therapy. Current research is ongoing in the use of lasers with chemotherapy to enhance the effects of chemotherapy but much information about the mechanisms still has to be learned. In the future, laser therapy may be used to dilate the vasculature to the tumor so that intravenous chemotherapeutics can attain higher doses in the parenchyma of the tumor with lower overall systemic doses given.17 Laser therapy has not been documented to cause neoplasia.18,19 While reactive oxygen species are required for mitochondrial function, over use of therapeutic lasers can increase reactive oxygen species to a level greater than the mitochondria and cellular enzymes such as

superoxide dismutase and catalase can handle resulting in depletion of ATP, influx of Ca++ into the cell and disruption of cellular processes.20 This could result in delayed healing. With treatment many patients will feel tired or even painful the day after, these symptoms are not evidence of an overdose and are most likely the result of stimulation of the tissues locally and systemically. Dosage and Wavelength Laser therapy is governed by the arndt-Schulz law in that weak stimulation with the laser increases cellular activity and strong stimulation inhibits it. With laser therapy the longer the laser is on the area being treated the more likely you are to over stimulate the tissue and retard physiological activity. The optimum dose for open wounds is thought to be 0.5-1.0 J/cm2 and for tissues with overlying skin 2.0-4.0 J/cm2. However, there is some individual variation with each patient and one should start with a low dosage to prevent inhibition of cellular activity.1 Another complication is the power of the laser. More powerful (watts) lasers will give a better response and therefore, also must be used for shorter periods of time. Most therapy lasers come with standard protocols for veterinary, small animal and equine uses such as open wounds, osteoarthritis, and bone healing. For the GaAIAs laser unit the following formula can be used to determine the time of treatment required: t=DxA/P x (1+d) D is the dose wanted in J/cm2, A is the area treated in cm2, P is the power in watts, and d is the depth of 1 to 4 cm. One also must remember that deep tissues can only be reached and the outer layers penetrated by using infrared (wavelength) laser beams. Another consideration is what effect does the laser therapist want to achieve? Pain relief requires higher doses than, for example, wound healing. By taking these points into consideration the formula above is still a guideline and not an absolute maximum or minimum dose to use.1 Treatment Intervals There are no definitively defined intervals to use between doses administered but moderate doses 3 to 4 times per week are more effective than higher doses in a shorter time period. As a general guideline, acute conditions including postoperative inflammation and pain can be treated with fewer doses in closer time intervals, whereas chronic conditions respond more to treatments that are spread out by one to several days. Generally we start out at 3 treatments per week, then go to 2 treatments per week and finally one treatment for one to several weeks. In some cases, following no response with 4 to 5 treatments, discontinuing therapy for several weeks and then beginning again can gain a response. In some cases laser therapy prior to the trauma, for example surgery, can be just as beneficial as performing laser therapy after the insult.21 Investigations studying the effects of lasers used preoperatively are being conducted. Lasers are often used in the first 48 hours postoperatively to open calcium channels, increase cellular proliferation, and stimulate wound healing. Macrophages will increase their release of growth factors when stimulated with a therapeutic laser.22 Dosages used in small animals for acute injuries (less than 72 hours old) are usually less than 2 J/cm2, whereas subacute injuries often receive 3 to 4J/cm2. Tendonitis, osteoarthritis and muscles spasms can be administered higher doses of 5 to 8 J/cm2.23 Antioxidants In some investigations administration of antioxidants inhibits or can reverse the beneficial effects of laser therapy.24,25 In contrast, antioxidants can be used if overdose of laser therapy is suspected.

Conclusions Laser therapy in veterinary medicine is still in its infancy, despite the many investigations that have been performed on laboratory animals and clinical patients. More blinded, placebo controlled clinical trials need to be performed before advocating its use routinely in practice. References 1. Tuner J, Hode L: The Laser Therapy Handbook. Grangesberg, Sweden, Prima Books AB, 2004 2. Baxter GD: Therapeutic LasersChurchill Livingstone, 1994 3. Karu TI: Molecular mechanism of the therapeutic effect of low-intensity laser radiation. Lasers Life Sci 2:53, 1988 4. Karu TI, Afanasyeva NI: Cytochrome oxidase as primary photoacceptor for cultured cells in visible and near IR regions. Dokl Akad Nauk (Moscow) 342:693, 1995 5. Karu TI: Local pulsed heating of absorbing chromophores as a possible primary mechanism of lowpower laser effects, in Galletti G, Bolangnani L, Ussia G (eds): Laser applications in medicine and surgery. Bologna, Monduzzi Editore, 1992 6. Brown GC: Control of respiration and ATP synthesis in mammalian mitochondria and cells. biochem J 284:171, 1992 7. Rubinov AN: Physiological grounds for biological effect of laser radiation. J Phys D: Appl Phys 36:2317-2330, 2003 8. Zhang Y, Song S, Fong CC, et al: cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated by red light. J Invest Derm 120:849-857, 2003 9. Wakabayashi H, Hamba M, Matsumoto K, et al: Effect of irradiation by semiconductor laser on responses evoded in trigeminal caudal neurons by tooth pulp stimuilation. Lasers in Surgery and Medicine 13:605-610, 1993 10. taguchi T, al. e: Thermographic changes following laser irradiation for pain relief. J Clin Laser Med Surg 9:143, 1991 11. Maeda T, al. e: Histological, thermographic, and thermometric study in vivo and excised 830 nm diode laser irradiated rat skin. Laser Therapy 2:32, 1990 12. Haina D, al. e: Temperature of the skin following application of softlaser. Laser in Medicine and Surgery 4:26-29, 1988 13. Dima FV, Vasiliu V, Ionesceu MD, et al: Studies on some biological functions of macrophages activated by NeHe laser photodynamic treatment as compared to coryne-bacterium parvum and interferon activation. Laser Therapy 5:117-124, 1993 14. Stadler I, Evans R, Kolb B, et al: In vitro effects of low level laser therapy at 660 nm on peripheral blood lymphocytes. Laser in Medicine and Surgery 27:255-261, 2000 15. Lindholm AC, Swensson U, de Mitri N, et al: Clinical effects of betamethazone and hyaluronan and of defocalized carbon dioxide laser treatment on traumatic arthritis in the fetlock joint of horses. J Vet Med:189-194, 2002 16. Parrado C, Carrillo de Albornoz F, Vidal L, et al: A quantitative investigation of microvascular changes in the thyroid gland after infrared laser radiation. Histol Hisopathol 14:1067-1071, 1999 17. Tamachi Y: Enhancement of antitumor chemotherapy effect by low level laser irradiation. Tokyo Medical College Newsletter:888-893, 1991 18. Shefer G, Halevy O, Cullen M, et al: Low level laser irradiation shows no histopathological effects on myogenic satellite cells in tissue culture. Laser Therapy 11:114-118, 1999 19. Moore K: Laser therapy in post-herpetic neuralgia. Laser Therapy 8:48, 1996 20. Friedman H, Lubart R, Laulicht I, et al: A possible explanation of laser-induced stimulation and damage of cell cultures. J Photochem Photobiol B Biol 11:87-95, 1991

21. Pontinen P: LEPT for preoperative care and early rehabilitation, in Proc. 4th Congress of World Ass. for Laser Therapy. Bologna, Monduzzi Editore, 2002, pp 59-69 22. Shumway R: Rehabilitation in the first 48 hours after surgery. Clin Tech Small Anim Pract 22:166170, 2007 23. Canapp DA: Select modalities. Clin Tech Small Anim Pract 22:160-165, 2007 24. Lubart R, Breitbart H: Biostimulative effects of low energy lasers. 3rd Congress of the North American Association for Laser Therapy, Bethezda MD, 2003 25. Ohbayashi E, Matsushima K, Hosoya S, et al: Stimulatory effect of laser irradiation on calcified nodule formation in human dental fibroblasts. J Endod 25:30-33, 1999