Mechanisms

The advantage of therapeutic laser light is that it stimulates natural biological processes and mainly affects cells in a decreased oxidation-reduction (redox) reaction. A cell in a low redox stage is acidic, but after laser irradiation the cell becomes more alkaline and able to perform optimally. Healthy cells cannot significantly increase their redox situation and thus will not react strongly to the laser energy, whereas cells in a low redox situation will be stimulated.^1,2 The most essential effect may be the increase of adenosine triphosphate (ATP), the “fuel” of the cells, produced in the mitochondria.³ ATP is the end product of the Krebs cycle, where the photon-acceptor enzyme cytochrome-c oxidase is inhibited by nitric oxide (NO). Laser light will dissociate the binding between NO and cytochrome-c oxidase, allowing it to resume ATP production.⁴ This basic mechanism initiates a cascade of cell signaling, leading to an optimization of body functions.⁵

Dosage

The most difficult part of LLLT is to find the optimal dosage. The tissue dosage is expressed in fluence, or energy density, measured in joules per square centimeter (J/cm²). Multiplying the output power of the laser in milliwatts by the time of exposure in seconds equals the produced energy; for example, 50 mW × 40 seconds = 2000 millijoules (mJ), or 2.0 J.

Now that we have the energy (2 J), we need to know the size of the area being irradiated. If we are irradiating an area of 2 cm², the calculation is 2 J over an area of 2 cm², or 2/2 = a fluence, or energy density, or superficial tissue dose of 1 J/cm². Suppose the irradiated area was only 0.5 cm². An inverse relationship exists between spot size (size of irradiated area) and fluence. Decreasing the size of the irradiated area increases the fluence: 2 J divided by 0.5 cm² = 4. Thus the dose becomes 4 J/cm², because the energy was emitted over a smaller area, increasing the local intensity. Because the dose depends greatly on the spot size, a thin light probe will create high doses in J/cm².However, this does not necessarily mean that the energy applied to the tissue is high, only that the intensity of the light energy at the emitting end of the thin probe is high.

Now that we understand the difference between energy and dose, we face a more complex calculation: dose at target. If the target is 1 cm below the surface, there could be reflection, scattering, and absorption of the energy before it arrives at the target. It is therefore necessary to consider the depth of the target area and the type of tissue between the light and the target tissue. The main absorbers of these wavelengths are pigmented chromophores, such as the hemoglobin in blood; therefore highly vascular tissue will absorb these wavelengths well, and less vascular tissue will absorb these wavelengths poorly. Mucosa is transparent to these low-level wavelengths; bone is also rather transparent, whereas muscle tissue, with its rich blood supply, is not. Another complicating factor is the amount of another chromophore in the target tissue, melanin. Because melanin is a strong absorber of these wavelengths, more light energy may be superficially absorbed rather than reaching deeper tissue, which may create local heating and even pain.

Therefore, the use of J/cm² to describe the dose in owner’s manuals can be confusing. The J/cm² (dose, fluence) indicates the intensity at the surface of the tissue but not the dose at the underlying target. A simpler approach is to use the term energy per point, calculating only the number of joules in each point. For clinical use, this is acceptable, but for scientific investigations, unacceptable. A “point” is often referred to as the size of the tip of the laser probe (spot size). The relationship between spot size and power density holds true for low-level lasers as well. A small spot size creates a larger concentration of the power per square millimeter or centimeter of tissue irradiated, whereas a wider spot size dilutes the same energy over a larger area.

Stimulation/Inhibition

Low-level laser therapy follows the Arndt-Schulz law: too small a stimulus does not trigger any effect. Increased stimulation augments the effect up to an optimal dose level. Increasing the dose even further means that the stimulation is gradually reduced, and at very high doses, stimulation is inhibited. The quest for the “optimal dose” is still not solved, but much is known about “therapeutic windows.” In some patients the goal is inhibition rather than stimulation, especially for pain management. High doses of laser light will inhibit the pain signals, partially by creating transient varicosities along the neurons, impeding signal transmission.⁶ Opioid-related mechanisms have also been reported,⁷ as well as a reduction in the compound action potential⁸ (Figures 15-3 to 15-5).

FIGURE 15-3 • A, Neurons before low-level laser irradiation. B, Neurons after irradiation, using 830-nm wavelength for 120 seconds. Note varicosities that formed along axons. These varicosities are transient but are thought to be obstacles in neural transmission.

(Courtesy Roberta Chow.)

FIGURE 15-4 • Varicosities formed along the axons after Nd:YAG laser irradiation.

(Courtesy Ambrose Chan.)

FIGURE 15-5 • Graph illustrating Arndt-Schulz law. Weak to moderate stimuli activate physiological processes. Strong stimuli (doses >10 J/cm²) inhibit physiological responses. Therapeutic window is therefore between 0.01 and 10 J/cm².

Acute vs. Chronic conditions

The general rule is to apply high doses of laser energy to acute conditions that present with inflammation and edema, treating chronic conditions (e.g., wounds, paresthesias, pain) more conservatively. Initially, acute conditions can often be treated until they resolve, whereas chronic conditions should be treated only once or twice weekly. Low-level laser doses are cumulative, which means that the dose given on day 1 lingers in the tissues on day 2 and adds to the long-term buildup of inhibitory levels.

Patients with long-standing chronic pain conditions may experience a flare of pain after LLLT. This is transient and actually shows that the patient is responding well to the treatment. The chronic situation is believed to be transformed into an acute phase, allowing healing to begin. Pain levels are reduced below baseline within 24 hours. The patient should be informed about this possibility before treatment. Other chronic pain patients may respond with deep fatigue, interpreted as an accumulated lack of rest, surfacing when the pain subsides. As with pharmaceuticals, the reaction and dosage must be individualized for each patient (Figure 15-6).

FIGURE 15-6 • Cumulative effect of dosing in low-level laser therapy (LLLT). A, With several days between doses, the total accumulated dose does not reach an inhibitory range. B, When doses are given too closely together, the accumulated dose reaches an inhibitory range. Such treatment inhibits rather than activates healing, according to the Arndt-Schulz law.

Pulsing

The importance of pulsing the light is obvious when applied to cell monolayers in the laboratory.^9–11 The pulse repetition rate (PRR) also helps in the clinical setting, although little is known about pulsing in vivo and animal/clinical studies are inconclusive. It is not yet known how to control these mechanisms through different PRRs. Also, the biological effects of a “chopped” CW laser beam and a superpulsed beam are different. At this time, use of a continuous beam is therefore recommended in units that have CW emission. The 904-nm GaAs laser does not have a CW mode, so a PRR must be selected, relying on anecdotal evidence to select pulse parameters.

Moriyama et al.¹² found more expression of the inducible nitric oxide synthase (iNOS) gene after 905-nm superpulsed laser irradiation. This suggests a different mechanism in activating the inflammatory pathway response in superpulsed mode compared with CW mode.

Number of Sessions

Several conditions can be resolved with a single LLLT session, but most conditions need repeated irradiation for optimal results. In the dental situation this is often problematic; patients may be unable to schedule brief laser appointments. Typically, the laser is used whenever the patient comes for routine dental treatment, such as for prophylaxis or cavity preparation. As a result, laser therapy might not be optimized. In many cases the irradiation can be delegated to the assistant or hygienist. In some situations the patient can borrow, rent, or buy a simple low-power laser (even a traditional 5-mW laser pointer) for a period to optimize the treatment by applying daily doses according to the dentist’s instructions (Figure 15-7).

FIGURE 15-7 • Patient with angular cheilitis treated by LLLT once in dental office (30 mW, 3 J, 650-nm wavelength) and at home by the patient (1 J daily) for 5 days. A, Preoperative view. B, Postoperative view.

Side Effects and Contraindications

Doses of laser energy near the therapeutic window will not cause negative effects. The worst result with LLLT is that nothing happens. There are few absolute contraindications for LLLT, but a few caveats.

Because LLLT affects blood flow in undefined ways, irradiation of patients with coagulation disorders should be avoided.^13,14 Presence of known malignancies is another contraindication, because LLLT stimulates cell growth. The literature also discusses pregnancy as a contraindication,¹⁵ although dentists work exclusively in the oral and head/neck regions. Also, although sometimes listed as a contraindication, pacemakers are electrical and not influenced by light. Some traditional safety regulations and contraindications seem to have been transferred from electrosurgical and other therapies to surgical lasers.

A contraindication especially relevant to dentistry is irradiation over the thyroid gland, located within the dental treatment area. Dentists generally are not informed about possible hyperthyroid or hypothyroid conditions, so direct irradiation over this area should be avoided. However, LLLT for thyroid disorders has been studied.¹⁶

Documentation

Because of the complex mechanisms behind LLLT, the literature is still not at an evidence-based level, except for a few indications. Still, more than 100 dental institutions worldwide are represented in the literature, comprising more than 3000 studies. Annually, about 250 papers on LLLT appear on PubMed, many on dental issues and most reporting positive results. Reports of no effect from LLLT can often be attributed to very low doses, miscalculation of the supposed dose, and ineffective treatment applications.¹⁷ Nevertheless, some qualified negative studies underline that LLLT is not a “hit and run” therapy but depends on knowledge of all the parameters. A correct diagnosis and sufficient dosage are key to success.

Power and Time

During the past decade, stronger lasers have been advocated as more effective, and thus lasers with output of 500 mW or more are marketed. For musculoskeletal conditions and pain therapy, high-output lasers may be useful, but for processes such as wound healing and bone regeneration, lower power over a longer time is more effective. Availability of power adjustments in a therapeutic laser, as with a surgical laser, is therefore helpful. Applying 5 J in 10 seconds with a 500-mW laser is quite different than applying the same 5 J with a 50-mW laser in 100 seconds. The 500-mW laser would work better for pain but might be less effective for treatment involving tissue regeneration.¹⁹ This reemphasizes why training is so important in the decision-making process.

Hygiene

Some therapeutic lasers have a removable, sterilizable probe, similar to that of the dental curing light. If this is not available, the probe can be wiped with alcohol or a surface disinfectant that will not react with the optics of the device, then covered by cling film, intraoral camera plastic cover, thermometer cover, or similar disposable barrier protection.

Biostimulation

Although dental lasers such as the neodymium-doped yttrium-aluminum-garnet (Nd:YAG), carbon dioxide (CO₂), and erbium family are considered “hard” or “surgical” lasers, they may be producing a degree of biostimulation in the areas peripheral to the focal spot, where the energy is reduced to stimulatory levels (Figure 15-8).

FIGURE 15-8 • Various zones of effect surrounding the focal spot when using a surgical laser (CO₂, Nd:YAG, erbium, diode). At the focal spot, vaporization occurs. Concentric to that is a zone of coagulation, where the proteins in the tissue have absorbed energy and have coagulated, but have not been vaporized. Concentric to that is the zone of denaturation, where tissue proteins have absorbed a sufficient amount of energy to be heated to the point of denaturation, but have not absorbed enough energy to be coagulated. Concentric to that is the zone of photothermal effect, where the tissue has absorbed enough energy to be heated, but not otherwise affected. Concentric to that is the zone of photostimulation, where some low-level laser activity can be found.

Some of the positive effects observed with the hard lasers may be explained by biostimulation. Pourzarandian et al.^20,21 reported stimulation of human gingival fibroblasts by low-level Er:YAG irradiation, as well as increased prostaglandin E₂ (PGE₂) production through induction of cyclooxygenase-2 (COX-2) messenger ribonucleic acid (mRNA) in human gingival fibroblasts. Additionally, Er:YAG lasers may be used at lowest output and scanned at a slight distance (out of focus) to produce biostimulation. The problem with using these hard lasers in this manner is that no microprocessor informs the practitioner how to control the dosage, and the fibers are not adapted for biostimulation.

Biostimulation is not limited to the traditional near-IR wavelength window; such effects are even reported when using defocused CO₂ lasers.^22–24 The CO₂ laser has an extremely poor penetration through tissue because it is so well absorbed at the surface, and the biological effects reported on deeper tissues may first appear improbable. However, the coherent light is absorbed in peripheral microvessels, and the clinical effect observed shows that LLLT has primary effects at the target as well as systemic effects through blood and lymph circulation. Thus, with minimal calculation, the owner of a “hard” laser can have a “soft” laser for free. Least complicated is the surgical diode laser, with simpler calculations and wavelengths within the traditional range of biostimulation.

Photoactivated Disinfection

There is a growing interest in the combination of different dyes with therapeutic lasers. Neither the dyes nor the therapeutic lasers used alone will have an effect on bacteria, but in combination, singlet oxygen will be produced, which has a strong bactericidal effect.

The photoactivated disinfection (PAD) method is already commercialized and recommended for use in periodontal pockets, periimplantitis, deep carious lesions, and infected root canals.^24–28 The laser must work within the absorption range of the dye used and is generally in the red spectrum, with a power output of 50 to 100 mW. The selected dye is applied and allowed to diffuse for a few minutes, and then the laser is used. Some transient discoloration may be seen in dentinal and mucosal areas.

Curing Light

All dentists have a composite curing light, typically with a wavelength peak of about 470 nm. Energies delivered are within the low-level laser therapeutic window, but studies of the photobiological effect on the surrounding tissues are largely lacking.

In a 2009 in vitro study, Enwemeka et al.²⁹ demonstrated that light-emitting diode (LED) energy with a 470-nm peak successfully kills methicillin-resistant Staphylococcus aureus (MRSA). Irradiation produced a statistically significant, dose-dependent reduction in both the number and the aggregate area of colonies formed by each strain of cells. The higher the dose, the more bacteria were killed, but the effect was not linear, being more impressive at lower than at higher doses. Almost 30% of both strains were killed with as little as 3 J/cm². As much as 90.4% of the two different colonies were killed with an energy density of 55 J/cm². This study requires further in vivo investigation but suggests an innovative use of an available dental light source to treat MRSA infection, which has high morbidity and high mortality.

Noncoherent Light

Blue light, as in curing lights, has a bactericidal effect in general. Importantly, curing lights are noncoherent, whereas lasers are coherent. Whether or not coherence is important has long been discussed, and some claim coherence is not needed. This misunderstanding is based on in vitro studies using cell monolayer that emphasize wavelength and intensity, as discussed earlier.⁵ The in vivo situation is different, however, and thus far a relative equivalence between coherent and noncoherent light has only been documented for superficial conditions such as open wounds.

All light has a biological effect, even broadband noncoherent light, given the correct parameters and conditions. Studies comparing coherent and noncoherent light for deeper tissues to date favor coherent light. The excellent biological effects of noncoherent light have not been compared to coherent light.

The length of coherence is also important. The length of coherence from a gas laser such as a helium-neon (HeNe) laser is very long, whereas that from a diode laser of the same wavelength is much shorter. A comparison of the effect on gingivitis using HeNe on one side and red diode laser on the other side (both lasers emitting at the same wavelength) showed better results using the longer coherence but same wavelength HeNe. The difference probably can be minimized using higher energies with the diode. Coherence is not lost when light penetrates tissue. However, the length of coherence is split into small, coherent spots called “speckles,” found in all areas reached by the laser light.

Anesthesia

Applying LLLT to the mucosa before an injection results in a slight anesthetic effect, although this cannot be obtained in the hard palate.³² LLLT applied before the injection will also improve healing, should the needle cause trauma to a vessel or nerve. LLLT improves local microcirculation,^33,34 so the effect of the numbness can be shortened if LLLT is applied to the site after completing the dental procedure. From 4 to 6 J is needed in both cases.

Aphthous Ulcers

The healing time of aphthous ulcers can be shortened and the immediate pain reduced by administering 4 to 6 J over the lesion.^35,36 LLLT does not seem to be as effective for aphthous ulcers as the more aggressive approach using surgical lasers (see Chapter 6). Patients with aphthous ulcers should avoid toothpastes containing sodium lauryl sulfate, which may trigger these lesions in predisposed persons.

Edema

The lymphatic system plays an important role in the inflammatory process, and LLLT over the involved lymph nodes decreases edema. Start irradiation over the most distal nodes of the chain involved, and work toward the focus of the swelling, using 2 to 3 J per node. Reduction of large edemas requires high doses locally, preferably by IR low-level laser units. The permeability of the lymph vessels will be reduced, lumen size increased, and repeated irradiation will stimulate growth of collaterals^37–41 (Figure 15-10). The lymphatic system brings the lymphocytes and natural killer cells to fight the infection. Meneguzzo et al.⁴¹ reported that an 810-nm laser reduced rat paw edema whether the irradiation was performed in the paw itself or over the inguinal lymph nodes.

FIGURE 15-10 • A, Vein, artery, and lymphatic vessel before irradiation. Note diameter of the vessels. B, After low-level irradiation of vessels using laser with 904-nm wavelength. Note dilation of vessels, which leads to increased circulation in the region they supply.

(Courtesy Pierre Lievens.)

Endodontics

Use of LLLT does not have a bactericidal effect, and surgical lasers are the preferred instruments to reduce bacteria in infected root canals. Few manufacturers of therapeutic lasers offer probes that could reach the root canals. However, IR light can reach all apices, and visible red light can reach the more superficial apices through the mucosa and produce an antiinflammatory and pain-reducing effect.

Sousa et al.⁴² analyzed the effect of LLLT on the secretory activity of macrophages activated by interferon gamma (IFN-γ) and lipopolysaccharide (LPS) and stimulated by substances leached from an epoxy resin–based sealer (AH-Plus) and a calcium hydroxide sealer (Sealapex). The production of tumor necrosis factor alpha (TNF-α) was significantly decreased by LLLT, regardless of experimental group. The level of secretion of matrix metalloproteinase-1 (MMP-1) was similar in all groups.

Laser application after overinstrumentation and overfilling is a good example of an indication for LLLT in endodontics. Because LLLT can stimulate bone formation, apical bone resorption probably can heal faster after completed endodontic treatment if LLLT is applied. Energy needed is related to the depth of the apex, ranging from 4 to 8 J per apex. For the same reason, intraoperative and postoperative LLLT in apical surgery has potential,^43,44 but solid scientific documentation is still lacking. However, irradiation over the suture line will stimulate fibroblast proliferation and increase tensile strength.⁴⁵

In patients with acute pulpitis, when the affected tooth or root is difficult to pinpoint, the laser can be applied over the apices in the involved area. The affected tooth may react by a pain increase, probably because of increased microcirculatory pressure in the pulpal chamber. LLLT can also be used as an adjunct therapy in pulp capping^46,47 and pulpotomy^48,49 (see Chapter 12). In both cases the exposed pulp is irradiated at low intensities, applying 2 to 3 J before traditional methods are used. The irradiation will reduce inflammation, preserve odontoblastic integrity, and stimulate cellular proliferation.

Extractions

Nontraumatic approaches and good postoperative procedures are the key to satisfactory healing after extractions. However, the occasional complication is unavoidable. Adding LLLT after the extraction will reduce the inflammatory phase, induce pain reduction, stimulate the fibroblasts in the wound periphery, and stimulate the osteoblasts in the socket.^50–55 High doses of laser energy can focus on the postoperative pain, but to obtain a good healing process, lower power and longer time are more advantageous.

The major goal of LLLT after extractions is to stimulate the fibroblasts to seal the socket. In cases of failure (dry socket), the traditional methods are used in combination with high doses of LLLT to reduce patient discomfort. When the dressing is changed during subsequent appointments, lower doses are given to stimulate fibroblast growth. Not only does LLLT stimulate fibroblast proliferation, but the cells are arranged in parallel bundles as well, creating a smoother area.² This is of particular interest in extraoral surgery when the cosmetic aspect is important (Figures 15-11 to 15-13).

FIGURE 15-11 • A, Socket immediately after tooth extraction. B, Extraction socket after laser irradiation using 650-nm wavelength at 30 mW, 8 J, 1 day after extraction.

(Courtesy Talat Qadri.)

FIGURE 15-12 • A, Fibroblasts in a cell culture. Note random alignment of the cells. B, Fibroblasts after LLLT using 780-nm wavelength. Note arrangement of fibroblasts in parallel bundles. This may have implications for wound healing and cosmetic procedures.

(Courtesy Luciana Almeida Lopes.)

FIGURE 15-13 • A, Two identical lasers for treatment of extraction sockets. Top laser has its aperture taped closed and will be used as a “sham” laser (control). B, Preoperative view of maxillary third molars. Left side was irradiated with 2 J before extraction. Right side was “sham irradiated” with taped laser. After extraction, both sockets were irradiated with 2 J by sham laser. C, One-day postoperative view of extraction sockets. Note left socket treated with LLLT has smaller socket opening with more coagulum. Preextraction irradiation is used to reduce edema and inflammation and to stimulate fibroblast proliferation; less edema = less pain; more fibroblast proliferation = faster healing.

Herpes Simplex Virus

Patients with a herpes simplex virus type 1 (HSV-1) eruption may be reluctant to visit the dentist. However, LLLT is the most efficient method of treating this infection.^36,56–58 In particular, if treated during the initial prodromal stage (when the patient feels the initial tingling), the healing will only take a few days or may even disappear within hours. Importantly, patients with recurrent HSV-1 attacks will experience longer intervals between the outbursts. Large blisters can be opened with surgical lasers (e.g., erbium, CO₂) to empty the fluid/>