{"id":5912,"date":"2015-12-28T09:34:55","date_gmt":"2015-12-28T09:34:55","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=5912"},"modified":"2020-04-25T06:22:44","modified_gmt":"2020-04-25T06:22:44","slug":"low-level-laser-therapy-for-the-treatment-of-chronic-wound-clinical-considerations","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol8no2\/low-level-laser-therapy-for-the-treatment-of-chronic-wound-clinical-considerations\/","title":{"rendered":"Low Level Laser Therapy for the Treatment of Chronic Wound: Clinical Considerations"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Wounds are among the most common\u00a0health problems worldwide. Traumatic scars and\u00a0surgical cicatrix form a wide range of acute and\u00a0chronic wounds, associated with increased\u00a0morbidity (1). The significant impacts of wounds\u00a0incidents on physical and mental health usually\u00a0drive scientists to find efficient treatments. The\u00a0classification of wounds into acute and chronic types
\nis a key to know the medical guidelines and\u00a0especially the quality of therapeutic cycles in wound\u00a0treatment. More specifically, surgical wounds are\u00a0superficial or deep wounds on skin, mucous\u00a0membranes, fascia, and muscle layers.\u00a0In conventional wound treatment some\u00a0specific drugs such as topical administrative ones\u00a0are used (1). Relatively high prevalence of wounds\u00a0and high costs of conventional methods as well as\u00a0emergence of drug resistance of chronic wounds\u00a0have boosted the rapid raising of alternative wound\u00a0healing methods. During the last decade several\u00a0methods based on laser, electric and magnetic\u00a0fields, light, and ultrasound have been developed\u00a0as an alternative or adjunctive treatment for chronic\u00a0and acute wounds treatment (2-7). Despite the\u00a0limited therapeutic window of low level laser\u00a0therapy (LLLT) in some patients, laser seems to be\u00a0a promising hope for many patients. To develop\u00a0any therapeutic modality, knowing the basic\u00a0physical and physiological characteristics of the\u00a0target tissue is the first step (8). To evaluate the\u00a0wound tissue, study the four basic topics is\u00a0necessary: history of wound, history and types of\u00a0previous therapeutic methods, history and types of\u00a0health-care procedures for wound management,\u00a0history of previous wound.<\/p>\n

Irrespective to whether the wound is\u00a0superficial or deep, plasma leakage provokes the\u00a0body\u2019s immune system to activate especial parts of\u00a0coagulation cascade and inflammatory system\u00a0which in turn (associated with the formation of
\nprostaglandins as a result of the effect of\u00a0cyclooxygenase on membrane phospholipids),\u00a0through accumulation of serous exudates. During\u00a0this process, the inflammatory phenomena are<\/p>\n

moderate. Gradually, as a result of cooperation of\u00a0different compound systems, the basal epidermis\u00a0tissue begins to form epidermis scars. After that,\u00a0granulation tissue forms dermis scars due to the\u00a0stimulation of fibrogenesis by adult connective cells;\u00a0specific mechanism of these cells is their change\u00a0into fibroblast replacing the fibrocytes by\u00a0themselves (2, 8-12).<\/p>\n

Factors like wound size including depth,\u00a0width and length, necrotic tissue type, exudate type\u00a0and amount, surrounding skin color, peripheral\u00a0tissue edema and granulation tissue are the main\u00a0parameters determining an appropriate technique\u00a0for wound healing(8) (13).<\/p>\n

Skin is composed of five main layers. The\u00a0fibroblast layer of the skin includes two main\u00a0proteins; collagen and elastin. The main rule of\u00a0these elements is the protection of skin\u00a0steadfastness. Any trauma damaged this layer\u00a0caused the skin to lose its consistency. When the\u00a0injury extends down through dermis layer by\u00a0passing from keratinocyte, the vessels endothelium
\ndamaged. Now the acute inflammatory phase of\u00a0the body begins and blood vessels dilation allows\u00a0migration of especial blood components like\u00a0monocyte and platelet to the area of the injury (10).<\/p>\n

It is important to describe whether the\u00a0wound is a full thickness or not, because the wound\u00a0extending through dermis, may involve\u00a0subcutaneous tissue and possibly bone and\u00a0muscles. In full thickness wound, bone, tendons,\u00a0and muscles may not be exposed. In some cases,\u00a0slough may be seen which does not obscure the\u00a0depth of tissue loss (9, 14).<\/p>\n

Some wounds include necrotic tissues;\u00a0most of the time hyperglycemia in diabetic patients\u00a0causes infection, progressive, and necrotic wounds\u00a0after a simple injury. The main characteristic of such\u00a0wounds is that the wound depth cannot be
\ndiagnosed if necrotic materials or debris cover the\u00a0ulcer (14).<\/p>\n

Wounds Treatment<\/strong><\/p>\n

Several medications are used for the\u00a0treatment of wounds (15-19). However, each drug\u00a0has its own side effects in addition to the gradual\u00a0increase in drug-resistant behaviors in wound\u00a0treatment.<\/p>\n

To develop and optimize an efficient LLLT\u00a0technique it is essential to determine the exact\u00a0mechanisms of action and interaction of laser with\u00a0living tissues. In this regard, several animal studies\u00a0have been performed (5, 10, 20-22). These studies\u00a0showed that hyperglycemia and acidosis delay the\u00a0wound healing. Laser irradiation can inhibit this\u00a0process with no serious or bloody exudates (23).<\/p>\n

Studies investigating the laser as an adjunctive or\u00a0alternative treatment for surgical wounds have\u00a0shown its efficacy in enhancing surgical closure,\u00a0reducing infection and pain, and shortening the\u00a0overall wound healing period. Laser therapy\u00a0showed a promising outcome in the treatment of\u00a0lower extremity venous ulcer as an adjunctive\u00a0treatment of standard therapy (15). However, the\u00a0same protocol failed in the treatment of pressure\u00a0ulcers (15). Different parameters (wavelength,\u00a0power, energy, pulse frequency, pulse duration, etc)\u00a0and irradiation conditions like exposure time,\u00a0frequency, and duration of treatment influence the\u00a0treatment outcome (3, 24-26). Therefore, to develop\u00a0a successful treatment appropriate selection of\u00a0these parameters is necessary.<\/p>\n

LLLT and Wound Treatment<\/strong><\/p>\n

Therapeutic effects of LLLT for treatment\u00a0of injured tissues and suppression of pain, make\u00a0this technique to be promoted as a form of laser\u00a0medicine which use low level (low power) laser or\u00a0light emitting diodes to alter cellular functions (6,\u00a014). The benefits of LLLT have been proved to be\u00a0considerable in acute pain treatment, improvement\u00a0of tissue scars resulting from surgical incision\u00a0through promotion, fortification, and commissioning\u00a0of cellular cycle to generate productive and\u00a0substitute cells (6). The main areas of application of\u00a0LLLT in medicine are represented in Figure 1 (10).<\/p>\n

Low-dosages of laser which are used in\u00a0LLLT affect enzymatic chain reactions, cellular\u00a0immunity, the quantity and quality of immune cells,\u00a0cell proliferation process, tissue secretions, etc by\u00a0the least systemic side effects and the most
\nsufficient therapeutic impressions(23, 27).<\/p>\n

LLLT Physical Parameters<\/strong><\/p>\n

The most important physical characteristic\u00a0of laser, making it appropriate for medical therapy,\u00a0is the dissemination of electromagnetic radiation\u00a0with particular properties; monochromaticity\u00a0coherence and low divergence. The intensity of
\nlaser, which is correlated with its spectral distribution,\u00a0is known as monochromaticity; though for LLLT\u00a0purposes, this is not a critical parameter. An\u00a0operational scheme of laser can be described by\u00a0the excitation of a medium through the introduction\u00a0of energy(13, 28). The most significant interaction\u00a0between the laser beam and tissue is absorption.\u00a0Because of the absorption bands broadness, thereis no specific essential to have a spectrally narrow\u00a0laser (13, 28).<\/p>\n

Laser – Biological Tissue Interaction<\/strong><\/p>\n

Like any other electromagnetic treatment,\u00a0the primary effects of laser interaction with a\u00a0biological tissue are divided into thermal and non\u00a0thermal. LLLT is basically a non thermal energy\u00a0application. Although delivery and absorption of any\u00a0energy to the body will produce heat in some extent,\u00a0non thermal in this context means no accumulative\u00a0thermal energy occurs or temperature elevation in\u00a0macroscopic scale is averaged zero.\u00a0Photobioactivation is a common term for LLLT and\u00a0indicates stimulating various biological events\u00a0using light energy without significant temperature\u00a0changes. There are some other alternative terms\u00a0such as photobiostimulation and\u00a0photobiomodulation. When a laser beam, or- a\u00a0photon, alters the energy level of an atom through\u00a0shifting between e2 and e3, this event establishes a\u00a0change in physicochemical cellular function which\u00a0acts as a trigger agent for beginning a mimicry\u00a0cascade system. A second photon that will be in\u00a0phase, propagate in the same direction as the\u00a0excited photon. This phenomenon, that is called\u00a0stimulated emission, is the basic of laser light\u00a0generation. It has been mentioned that in most of\u00a0the biological tissues, photons are preferably\u00a0scattered in forward direction.<\/p>\n

The laser light possesses some unique\u00a0characteristics making it appropriate for different\u00a0medical applications. The most important features\u00a0include monochromacity, coherence, and\u00a0polarization. Of these, monochromacity is the most\u00a0important parameter influencing the therapeutic\u00a0effects. Previous studies have proposed three main\u00a0reactions for laser-tissue interactions:\u00a0photochemical, photothermal and photoplasmal (5,\u00a06, 29). In photochemical reaction, the cell\u2019s function\u00a0is inactivated temporarily, due to the very low-power\u00a0irradiation that induced toxic chemical procedures.<\/p>\n

In this kind of interaction, light is absorbed by tissue\u00a0chromophores, besides, the increase of local\u00a0temperature, triggers the process of heat\u00a0transmission (conduction) to cooler areas.\u00a0Noticeably, greater degree of heat may possibly\u00a0lead to denaturization, necrosis and even\u00a0vaporization and spallation (29, 30)\u00a0Irradiation of low intensity visible light can\u00a0change the activity of biomolecules such as DNA\u00a0and RNA, but these molecules do not absorb the\u00a0light directly. The cell membrane is probably the\u00a0primary absorber of the energy which then\u00a0generates intracellular effects through a second\u00a0messenger or cascade type response. The\u00a0magnitude of this photoresponse is reportedly\u00a0determined in part by the state of the cells\/tissues\u00a0prior to irradiation, summarized in a simple\u00a0statement that \u2018starving cells are more\u00a0photosensitive than well fed ones\u2019. The laser light\u00a0irradiation of the tissues is seen then as a trigger\u00a0for the alteration of cell metabolic processes, via a\u00a0process of photosignal transduction. The often cited\u00a0Arndt-Schults Law supports this proposal.<\/p>\n

Several studies have been conducted to\u00a0shed more light on the understanding of the\u00a0mechanism of actions of laser medicated wound\u00a0treatments (1, 3, 9, 16, 28). Various physiological\u00a0and cellular mechanisms of laser-tissue interaction\u00a0have been proposed. However, as the majorities of\u00a0these studies were in vitro, realistic assumptions\u00a0should be adapted in generalizing the findings into\u00a0the living mammalian tissues.<\/p>\n

The main physiological and cellular\u00a0effects of laser-tissue interaction are modulation of\u00a0cell proliferation, cell motility, activation of\u00a0phagocytes and macrophages, stimulation of\u00a0immune responses, increasing cellular metabolism,\u00a0modulation of proliferation of fibroblasts, alteration\u00a0of cell membrane potentials, stimulation of\u00a0angiogenesis, alteration of action potentials, and\u00a0alteration of endogenous opoid production.<\/p>\n

Clinical considerations of LLLT in wound<\/strong><\/p>\n

Currently, in clinical settings LLLT is used\u00a0for different types of wounds as adjunctive or\u00a0alternative treatment when there is no definitive\u00a0drug treatment (6, 8). Several clinical trials have\u00a0been conducted to investigate and develop the LLLT\u00a0for chronic wounds (25, 31, 32). Among the others,\u00a0numerous studies were allocated to the diabetic\u00a0wounds; because the necrotic tissue due to\u00a0hyperglycemia set aside the highest range of\u00a0morbidity to themselves like cutaneous wounds\u00a0including excoriation, superficial and deep wounds\u00a0due the venous and arterial obstruction (33).<\/p>\n

One of the problems in use of LLLT is the\u00a0application of optimal dose of exposure (34). The\u00a0lots of inquiry have accomplished on tissues, proved\u00a0the depth of laser penetration to be different in\u00a0various tissues, the oral mucosa is quite transplant\u00a0as the wavelength and does not absorb light well,\u00a0bone and skin are approximately the same as\u00a0mucosa, whereas muscles absorb the most light\u00a0(6, 35). LLLT can be used in such classification as\u00a0abrasions knife cuts, Para-scrotal wet eczema,\u00a0necrotic wounds, and inflammation (6, 35).<\/p>\n

LLLT has analgesic, vasodilating and antiinflammatory\u00a0properties (9). Usually, drug\u00a0administrative and surgical methods are associated\u00a0with pain, swelling, scars and secretions of wound\u00a0individually but lasers can affect the whole factors;\u00a0for example laser stimulates microcirculation which\u00a0leads to the change of capillary hydrostatic pressure\u00a0that may results in absorption of edema and\u00a0eventually eliminating of inflammatory metabolites\u00a0(8, 25, 36).<\/p>\n

Dose Considerations<\/strong><\/p>\n

One of the main challenges in developing\u00a0laser therapy in the clinical setting is contradictions\u00a0in defining one global dose units. Different studies\u00a0have reported different units of doses. In addition\u00a0different laser machines work with different units\u00a0such as Joules\/ cm2, Joules, Watts, watts\/cm2, etc.\u00a0The most critical and reliable dose unit for laser\u00a0therapy is energy density in J\/cm2. Few devices\u00a0enable the practitioner to set the dose in J\/cm2.<\/p>\n

However, most recent studies and evidence have\u00a0argued that Joules (energy) may be the most critical
\nparameter rather than energy density. For dose\u00a0calculation, some machines offer on board\u00a0calculation and other machines require the operator\u00a0to make calculations. The common considerations\u00a0for dose calculation are summarized in Table 1.\u00a0The most guidelines suggest that the\u00a0energy density per treatment session should be\u00a0within the range of 0.1 – 12.0 J\/cm2. However, there\u00a0are some instructions, for special diseases and\u00a0exposure conditions that recommend up to 30 J\/\u00a0cm2.<\/p>\n\n\n\n
\"Fig.<\/td>\nFigure 1: Schematic representation of the main areas of application of LLLT (10)<\/strong><\/p>\n

Click here to View figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

It has been previously suggested that a\u00a0maximal (single treatment) dose of 4 J\/cm2 should\u00a0not be exceeded. The evidence would not support\u00a0that contention. Again as a generality, lower doses\u00a0should be applied to the more acute lesions which\u00a0would appear to be more energy sensitive.<\/p>\n

LLLT Advantages over other treatments<\/strong><\/p>\n

The process of wound healing is a\u00a0dynamic and intricate procedure which considered\u00a0as a natural response to any injury occurs in live\u00a0tissues. An initial factor for reaching to the successful\u00a0and efficient treatment of wounds is following post\u00a0treatment procedure and assessment of the entire\u00a0patient (27).<\/p>\n

Clinicians usually attach more importance\u00a0to this clinical operation in drug administrative\u00a0methods. Drugs which are usually administered in\u00a0wound healing have both systemic and localized\u00a0impressions. Systemic effects and also side effects\u00a0of drugs require specific evaluation. By application\u00a0of LLLT, we have this opportunity to affect specific\u00a0areas so the risk of any systemic effects especially\u00a0on vital organs will be elicited (35).<\/p>\n

Electrical and magnetic stimulations are\u00a0the two main techniques used for wound healing\u00a0(2, 11). Electrical stimulation is an adjunctive\u00a0therapy that is underutilized in plastic surgery and\u00a0could improve flap and graft survival, accelerate
\npostoperative recovery and decrease necrosis. It\u00a0also has been suggested to reduce infection and\u00a0improve cellular immunity. Enhancing the perfusion\u00a0of tissue as an additional effect of electrical\u00a0stimulation, help expedite wound healing.<\/p>\n

Obviously one of the problems which\u00a0appear in wounds is insufficient oxygen supply; this\u00a0will prevent normal healing process. Additional\u00a0oxygen supply to wounds particularly necrotic ones\u00a0as in diabetic ulcers will accelerate healing\u00a0procedure.<\/p>\n

It has been shown that LLLT helps to\u00a0eliminate hypoxia and the ischemia had been\u00a0induced to the tissue by means of obstruction of the\u00a0vascular system(22, 37).<\/p>\n

Future Perspectives<\/strong><\/p>\n

According to the wide range of LLLT\u00a0application specifically in the field of wound healing,\u00a0now laser therapy is not just a science, but an\u00a0amenable technique for almost any kinds of wound.\u00a0Therefore for the purpose of achieving better results;\u00a0researches are underway that will help to improve\u00a0the techniques and devices used for laser therapy
\n(7).<\/p>\n

Clinical application of laser is easy by the\u00a0specialists and fortunately can be well tolerated by\u00a0the patients. Though, scientists continue to get\u00a0supportive data and wound related researches for\u00a0both enhancing LLLT therapeutic quality and\u00a0frustrating or at least minimizing the adverse effects\/\u00a0side effects (25, 31, 32, 38-40).<\/p>\n

Hopefully by further trials and researches,\u00a0LLLT will be investigated to determine if it can be\u00a0well efficient in augmentation of other regenerative\u00a0therapies such as cell therapy, platelet rich plasma,
\nor skin grafting (39).<\/p>\n

Conclusion<\/strong><\/p>\n

Despite widespread studies on different\u00a0aspects of LLLT in wound healing, several main\u00a0questions still remain unanswered. The exact\u00a0mechanisms of laser-tissue interaction, crucial\u00a0parameters determining the therapeutic outcomes\u00a0and efficacy of LLLT on different chronic wounds\u00a0treatment are the main issues need further research.\u00a0LLLT shows high therapeutic efficacy for different\u00a0chronic wounds particularly skin wounds and\u00a0diabetic ulcers and necrotic wounds. Further\u00a0controlled trials in combination with molecular and\u00a0cellular level assessments are needed to expand\u00a0our knowledge on the exact mechanisms of action.<\/p>\n

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