Low level laser therapy in dentistry
Keywords:
laser,
medical,
fibers, Time:14-12-2015
Introduction
In medicine and dentistry, diode
lasers fibers have been used predominantly for applications which are broadly termed low level laser therapy (LLLT) or ‘biost i m u l a tion ’ ; 3 ho wev er, there is controve rs y su r rounding the effectiveness of some of these procedures.
The use of LLLT in dentistry is not new, and LLLT techniques have been in widespread use in Japan6 and in Europe7,8 for more than 10 years. Interest in LLLT in dentistry has been particularly high in the former Eastern block countries. In fact, the Russian literature has reports on LLLT which cover 30 years of experience with the technique,9,10 although this literature has remained largely inaccessible to the Western world. While much of this work has been done with helium-neon (HeNe) gas lasers, an identical laser wavelength (632 nm) can now be produced by diode laser devices. There have been many claims for the therapeutic effects of LLLT on a broad range of disorders. A short selection from the list of LLLT applications promoted by some users and manufacturers of LL L T devices includes: acceleration of wou n d healing, enhanced remodelling and repair of bone, re s t o r a tion of normal neural function followi n g in j u r y, norma l i z a tion of abnormal hormonal function, pain attenuation, stimulation of endorphin release, and modulation of the immune system.11,12 Published data on efficacy exist for some but not all of these applications, and this presents a dilemma to the clinician faced with decisions as to what constitutes appropriate therapy.
Absorption of laser energy in LLLT
The major absorbing structures for the red visible and near infra-red laser wavelengths used in LLLT are most likely proteins; however, the identity of the photoreceptors responsible for the biological effects of LLLT has not been resolved. Several studies have suggested that either elements in the mitochondrial cytochrome system or endogenous porphyrins in the cell are the energy-absorbing chromophores in LLLT.13,14 Since the tissue penetration of the laser energy used in LLLT can be in the order of 5-10 mm, both superficial and deeper structures can be affected. However, as the energy penetrates the tissues, there is multiple scatt e r ing by both eryt h r o c ytes and microvessels, and thus both blood rheology and the distribution of microvessels influence markedly the final distribution of laser energy.15 It is unclear whether the photobiological effects which occur with LLLT are specific to monochromatic coherent laser energy, or can be elicited by conventional light sources emitting non-coherent energy over a similar range of wavelengths.
Effects of LLLT on fibroblasts
At low doses (e.g., 2 J/cm2), LLLT stimulates proliferation, while high doses (e.g., 16 J/cm2) are suppressive.16,17 The same type of dose response is observed both in vivo and in vitro, and occurs with all common LLLT wavelengths.18 Fibroblast maturation and locomotion through the matrix is also influenced by LLLT,19 and this in turn ma y contrib ute to the higher tensile strengths reported for healed wounds.20 There are several mechanisms by which LLLT may stimulate the proliferation of fibroblasts. LLLT has been shown to stimulate the production of basic fibroblast growth factor (bFGF), a multifunctional polypeptide which supports fibroblast proliferation and differentiation. Fibroblasts irradiated with low dose LLLT show both increased cell proliferation and enhanced production of bFGF, while high dose LLLT suppresses both parameters,16,21 indicating a causal relationship between autocrine production of bFGF from fibroblasts and proliferation. A further effect of LLLT on fibroblasts which can influence the wound healing process is the transformation of fibroblasts into myofibroblasts, which are responsible for wound contraction. LLLT of gingival fibroblasts in culture has been shown to induce transformation into myofibroblasts as early as 24 hours after laser treatment.22 In terms of the effects of LLLT on fibroblasts, it is important to recognize that LLLT may affect immune cells which secrete cytokines and other growth-regulatory factors for fibroblasts. Macrophages, which are a key component of wound healing responses, are themselves prone to the effects of LLLT. Irradiation of macrophage cell lines in vitro using LLLT has been shown to release soluble factors which promote fibroblast proliferation,23 although the identity of the factors involved has not been determined.
Effects of LLLT on immune cells
Moreover, laser irradiation potentiates the proliferative response of peripheral blood lymphocytes to PHA.25 In healing wounds, activation of lymphocytes by LLLT may make them more responsive to stimulato r y mediato r s present in injured tissues. In both in vitro and in vivo systems, LLLT influences macrophage function by promoting the secretion of fac t o r s which enhance fibroblast proliferation.23 An additional effect of LLLT which has been observed in vivo is an enhancement of the phagocytic activity of macrophages during initial phases of the repair response (6 hours after trauma). This is thought to facilitate debridement of the wound, and thereby establish conditions necessary for the proliferative phase of the healing response to begin.
Effects of LLLT on epithelial cells
One possible mechanism by which LLLT may enhance wound healing in vivo is via stimulation of epithelial cells. LLLT increases the motility of human epidermal keratinocytes in vitro,28 and this would explain the finding that wound sites treated with LLLT show accelerated closure.29 Despite its effects on proliferation, LLLT does not alter normal ke r a ti n o c yte differentiation or the synthesis of ke r a tins, and thus does not interfere with the forma ti o n of a normal, functioning epidermis.30 Thus, clinical use of LLLT under conditions which enhance keratinocyte migration should not alter the ultimate integrity or differentiated function of the epidermis that migrates to cover the wounded area.
Effects of LLLT on bone cells
In the laboratory setting, LLLT using a HeNe laser exerts pronounced effects on proliferation, differentiation, and calcification of cultured osteoblastic cells, although there is a specific therapeutic window for these effects. Cell proliferation and DNA synthesis are increased by LLLT only when the cells are in a phase of active growth. LLLT causes increased accumulation of calcium and accelerates calcification in vitro.31 If the in vivo parallel holds true, LLLT of healing sites within bone would be expected to increase bone deposition and promote bone regeneration. In a study of wound healing after tooth extraction in a rat model, LLLT delivered on a daily basis for one week using a gallium-aluminium-arse n i d e (GaAlAs) laser, both increased fibroblast proliferati o n and accelerated formation of bone matrix were found.32 However, studies of the influence of LLLT on bone and connective tissue regeneration in the palate in a canine animal model failed to find an effect.33,34 While at first glance this would suggest major species variations in the response of bone cells to LLLT, in the case in point irradiation levels were low and LLLT treatments were administered every second day rather than daily. Whether LLLT exerts positive results on bone regeneration following tooth extraction in humans remains controver si a l , 35 although there are reports that the formation of granulation tissue during post-extraction healing is accelerated.
Effects of LLLT on the blood vascular system
Vascular spasm can result in tissue ischaemia, and has been linked to a range of painful conditions. In in vitro systems, LLLT can induce a prompt reduction in isometric tension of vascular smooth muscle, while the same effect can be induced by LLLT in vivo delivered through the skin to the underlying vessels.37 Relaxation of vascular smooth muscle may contribute to analgesic effects of LLLT.
Soft tissue applications of LLLT
Eva l u ating the literature describing clinical applications of LLLT is complicated by the wide variations in methodology and dosimetry between different studies. Not only have a range of different wavelengths been examined, but exposure times and the frequency of treatments also vary. The inclusion of sham-irradiated controls in clinical studies is an important element, since placebo effects can be dramatic, particularly in terms of the level of pain experienced following treatment. In the light of these caveats, it is nevertheless informative to look at selected clinical studies of LLLT in medicine and dentistry.
Effects of LLLT on musculoskeletal pathology
Low level laser therapy is currently used in the therapy of rheumatoid arthritis, chronic pain, and muscle strain in both human and vet e r in a r y medicine. Physiotherapy has been an area of particularly high utilization of LLLT.38 Although some trials of LLLT in musculoskeletal injuries,39 synovitis, arthritis,40 and chronic low back pain41 ha ve failed to demonstrate the efficacy of this treatment apporach, positive results have been obtained in similar trials involving patients with repetitive strain injury, carpal tunnel syndrome, and lateral epicondylitis (‘tennis elbow’).42,43 A comprehensive meta-analysis of the effects of LLLT on musculoskeletal pain has been published.44 Of 23 published trials of LLLT, 17 employed a controlled design and of these ten were double blind. Pooling the pain score data from 13 of these studies revealed only small differences in pain between LLLT and placebo treatments, although it should be recognized that pooling data from studies which used different methodologies and dosimetry is a questionable approach.
Wound healing
At high laser irradiances (9.3 J/cm2), these reparati v e processes are slowed and disturbed.47,48 Of interest, studies in which LLLT has been delivered pre-operati v ely (i.e., prior to wounding) have failed to show significant benefits.49 , 5 0 Major changes seen in wounds treated with LLLT include increased granulation tissue, early epithelialization, increased fibroblast proliferation and matrix synthesis, and enhanced neovascularization.51 Of note, daily treatment with LLLT is required to provide the maximal benefit. LLLT delivered every second day provides little benefit.33,52 In humans, anecdotal clinical observations and small case studies have suggested that LLLT (generally using HeNe lasers) stimulates wound healing. However, controlled clinical studies have produced somewhat conflicting results. In a clinical study of skin wounds in over 125 patients, LLLT increased the strength of the postoperative scar.49 Similarly, in a study of wound healing involving 152 diabetic patients with purulent injuries of skin and underlying soft tissues, LLLT of wounds resulted a shortened healing phase.33 In a third study, LLLT used in 512 patients with corneal wounds, burns, or ulcers resulted in accelerated healing compared with a reference group of patients who received conventional treatment.