Pain Relief of Aphthous Ulcers by Lasers: A Literature Review




Dr. Dolly Roukoz, Chir. Dent., DU de Pathologie et de Diagnostic Oraux
Dr. Nadia Skandri, DCD, DEMS en Pathologie Buccale
Dr. Chirine Chammas, Chir. Dent., DU de Pathologie et de Diagnostic Orauxz

Département de Pathologie et de Diagnostic Oraux, Faculté de Médecine Dentaire, Université Libanaise









Introduction



Aphthous ulcers or recurrent aphthous ulcer (RAU) or canker sores are probably the most common1 and affect 5 to 25% of the population worldwide.2-4 The term aphthous is defined as a breach in the oral epithelium which typically exposes nerve endings in the underlying lamina propria resulting in pain and soreness.5-6

Clinically, aphthous ulcer is characterized by shallow round or oval shape7 with a white-yellow base which is a fibrinous slough,8 a discretely elevated yellowish edge9 and a distinct irregular border with a narrow red halo. Their etiology and pathogenesis are still unclear and much discussed.10 Several factors are suspected including immunological disorders,1,5 genetics, hormonal imbalances, zinc and iron deficiencies, stress, nutritional deficiencies, food intolerances, cigarette smoking and Sodium Lauryl Sulfate.11-12 
Aphthous ulcers may be single or multiple,10,12 usually occurring on the non-keratinized and mobile mucosa, but are rare on gingivae or palate.11 They are usually painful during first three days and pain may interfere with eating, speaking, and swallowing. Recurrence is common, with 2 or 3 ulcers in each outbreak5,7,13-14 and a three-month recurrence rate as high as 50%.5 It can also occur as widespread lesions in association with systemic diseases including Behçet’s syndrome, gastrointestinal malabsorption disorders like Crohn’s and celiac diseases and immunodeficiency syndromes such as infection with the human immunodeficiency virus (HIV) or cyclic neutropenia.
The main goal of treatment is to decrease pain, healing time, number and size of the ulcers14 and to increase disease-free periods. Current treatment options include topical agent, systemic and topical steroids, corticosteroids, cauterization, antibiotics, and mouth rinses containing active enzymes. Laser can be an alternative treatment for aphthous ulcers. Most lasers used are diode, erbium (Er) and carbon dioxide lasers. 
Diode laser treat recurrent aphthous ulcers15 by photostimulation12 and banding. Their wavelengths between 800 and 980 nm16 primarily absorbed by tissue pigment (melanin) and hemoglobin. However, they are poorly absorbed by the hydroxyapatite and water.12,17
The erbium family offers both hard tissue and soft tissue applications.17 Erbium lasers share a common characteristic of high absorption of the wavelengths by water, hydroxyapatite, and collagen. It results in a “shaving” or “planing” of the tissue that clinically appears different than the deeper penetration ablation process seen with diode lasers.18 The depth of penetration of an Er laser using a 200 to 400 µs pulse width is in the range of 5 to 40 µm, and there is as little as 5 µm of residual thermal damage. This penetration depth is vastly different than the soft tissue lasers (diode, Nd:YAG) where tissue effects can be as deep as 500µm or more. For instance, the collateral damage produced by the Er:YAG laser is minimal because the energy absorbed in water and thermal damage is small (no charring), which may result in improved healing of the area.
The carbon dioxide laser (λ=10,600 nm) is highly absorbed by water and hydroxyapatite. It has a smaller penetration than the Er and the diode, but like the diode laser it has a thermal effect.
Lasers are used in pain relief of aphthous to provide immediate and long term results. This is achieved by two different modalities: “Low Level Laser Therapy” and “Photobanding”.


Low level laser therapy


Low Level Lasers Therapy (LLLT) also referred to as “biostimulation” and “biomodulation” was introduced to irradiate cutaneous wounds and to accelerate the healing process.9 However, the term “biomodulation” is more appropriate, since the therapy can not only stimulate, but also suppress biological process.19-20 
The clinician must consider which wavelengths are capable of producing the desired effects within living tissues5,21 LLLT have poor absorption in water, and thus penetrate soft and hard tissues from 3mm to up 15 mm.
LLLT are designated by several parameters: the dosimetry, the frequency of treatment session and the total doses.21-22 The dosimetry is expressed by J/cm2 and represents energy density. 
Energy (J) = Power (W) × Time (s)
The principles of LLLT are: I) the power must be ranged from 10 up to 500 mw;21 II) pulsed mode delivery will allow some cooling to occur in between pulses;20,23 III) suitable therapeutic energies range from 1-14 J/cm2; and IV) there is generally no heat or tissue heating involved in this therapy24
Several protocols and different dosimetry have been described while using LLLT in aphthous ulcer treatment. The recommended dosimetry for the treatment of aphthous is 4 to 12 J/cm2.9 In clinically less aggressive lesions, a dosimetry of 4 J/cm2 has proven to be sufficient. However, in larger, ulcerated and more aggressive lesions, the dosimetry should be proportional to the extension of the lesion (maximum of 12 J/cm2 per session). Moritz and collaborators recommend 2 J/cm2. 21 
Application mode is punctual, directly on the lesion in case of aphthous up to 5 mm. In larger ones, application should be made around the lesion. The treatment frequency is 2-3 weekly sessions, with a 24-hour interval until remission of pain. 
The protocol established by van As25 is described in table 1.






Different mechanisms have been suggested for the main therapeutic effects with LLLT. It accelerates wound healing, reduces pain by perhaps stimulating oxidative phosphorylation in mitochondria of the neurons and modulates inflammatory responses.6,14,21,23,25 
Increased blood flow to local tissues and capillary vasodilatation are effects seen after LLLT.
When it is delivered in appropriate dosage, energy of the protons from the LLLT is converted into photochemical, photophysical and photobiological effects. Photoreceptors (cytochrome c-oxidase) can absorb laser irradiation and transfer it inside mitochondria. This stimulates synthesis of ATP (cell energy) which is the product of cytochrome c oxidase and Krebs cycle, leading to increased cell activity26 such as lymphocyte stimulation and activation of mast cells. Also proliferation of various types of cells such as fibroblasts and macrophages is seen. All these combined factors promote anti-inflammatory effects and biostimulatory effects, thus enhancing wound healing as illustrated in fig.1.
The use of “hard lasers” in treatment of aphthous ulcers has been successfully reported by several studies. For example, a female patient (50 years old) treated with stress related RAU showed a rapid and long term relief following a CO2 laser application used in continuous mode at 1-1,5 W for 5s.22 Moreover, a total regression of the lesion occurred 4 days after laser treatment compared to 5-7 days with corticosteroid treatment.14,23,25 
Other authors have investigated the use of CO2 laser 1W of defocused continuous mode for 5-10 seconds in 15 patients with recurrent aphthous ulcers in comparison to the placebo.28 Both ulcers were covered with transparent gel without the use of anesthesics agent. They observed a significant difference in mean of pain values between the laser and placebo groups measured 24 hours after the intervention was administrated.28 The analgesic effect in LLLT is usually gradual, cumulative, and multisessional.28 Researchers compared drug therapy, laser treatment and a combination of both over five years found that laser diode used at low levels of energy (200 mW) cut the healing time in half when compared to a pharmaceutical method (Solcoseryl™).29 
Authors reported a reduction of the pain after single session of diode laser and a quicker healing using the third generation diode laser technology (940 nm) wavelength which absorbed strongly in hemoglobin and water. This wavelength corresponds to the peak absorption for oxygenated (arterial) blood in this region of the spectrum and also higher absorption into deoxygenated (venous) blood than 810 or 980 nm diode lasers, giving this laser type more efficiency. Diode laser with 940 nm wavelength combines the effect of thermal subablasive lasers with the wanted effect of LLLT.12 Single session of diode laser irradiation can be used to produce immediate, dramatic and sustained analgesic effect on RAU lesions, the lesion duration were significantly reduced to about 40% from that of control lesion.12
Authors reported a reduced recurrence of the aphthous in the same area when treated with LLLT by diode laser.15


Fig 1: Schematic representation of the effect of low level laser on wound healing27


Photobanding


The technique consists of the formation of a protective layer on exposed connective tissue. Diode, erbium and CO2 lasers can be used to treat aphthous by inducing this layer.30
Diode laser transverses the epithelium and penetrates 2-6 mm into the tissue wherever erbium and CO2 lasers are very superficial. When laser cutting is in progress, small blood and lymphatic vessels are sealed due to the generated heat, thereby reducing or eliminating bleeding and edema. Denaturated proteins within tissue and plasma are the source of the layer termed “coagulum” or “char”, which is formed because of laser action and serves to protect the wound from bacterial or frictional action. During 48-72 hours post banding, this layer becomes hydrated from saliva, swells and eventually disintegrates to later reveal an early healing bed of new tissue.20 This layer acts as a barrier and decreases pain that derives from inflammatory sensitization of small-diameter afferent nerve endings that form a plexus at the junction of the epithelial and subepithelial layers. Branches of this plexus extend upward, into the epithelial layer; thus, aphthous ulcer produces a superficial, focal, inflammatory lesion that is directly associated with exposed sensory nerve endings.12,28 Unlike the erbium tissue appearance, there is no white pox marking and very little visual indication that the lesion is being treated.30
The clinical application of the photobanding technique consisted of one sitting. The protocol established is as following:31

Photobanding with diode laser
Step 1: Application of topical gel anesthesia for three minutes
Step 2: Flashing of the topical gel anesthesia
Step 3: Drying of the ulcers with air spray 
Step 4: 2–3 watts pulsed 20–50 Hz non initiated tips. The application of the laser was done in non-contact mode with a distance of 2-3 mm between the laser tip and the ulcer surface for about 60 to 90 seconds. The laser beam was applied in a continuous sweeping, circular motion, so as to cover the entire ulcer. This application induced an anesthesia of the superficial layer.
Step 5: 0.6–0.8 watt, continuous mode, initiated tips. The surface of the ulcer is painted with the laser with simple fine touching. A black superficial layer is induced by the thermal effect of the diode laser.

A

B

C

Fig 2: Aphthous ulcer
(A) before treatment
(B) after diode photobanding (notice the brownish carbonized layer)
(C) wound healing 14 days after treatment



Photobanding with Er,Cr:YSGG

It is the same protocol as the photobanding by diode laser.
Step 1: Application of topical gel anesthesia for three minutes
Step 2: Flashing of the topical gel anesthesia
Step 3: Drying of the ulcers with air spray 
Step 4: Using the Er,Cr:YSGG laser (2,780 nm) in a non-contact mode, with very low power (0.75 watt) without water. The treatment area should be extended about 1mm outside the lesions boundaries. The laser energy is defocused above the lesion until small white areas are seen on the tissue, and allowed to remain for 15 seconds while using a circular motion over the entire area. The process can be repeated two or three times until the patient indicates the affected tissue no longer feels uncomfortable. The treatment is stopped when a superficial homogeneous white layer is achieved. This layer is contributed to the formation of superficial denaturating protein layer.
However large lesions may need a second treatment within 24 hours. No local anesthesia is required and the patient should get immediate relief.30


A

B


Fig 3: (A) Aphthous ulcer before treatment.
(B) The resulting white layer acting as a bandage


Conclusion


Oral aphthous ulcers were treated with different topical agents, but these treatments remain symptomatic. The use of lasers in techniques like LLLT and photobanding can be an alternative treatment. 
In fact, several studies demonstrate that LLLT is an effective modality for the treatment of aphthous ulcers. It reduces healing time and inflammatory reaction and provides immediate pain relief. Since aphthous ulcers are often recurring lesions, further studies reported a reduction of the recurrence of these lesions. Further experimental studies should be conducted comparing LLLT with other routinely used treatment modalities such as topical corticosteroids. New trials on LLLT in oral pathology should make use of standardized, validated outcomes, and should explore how the effectiveness of the LLLT protocol used may be influenced by wavelength, treatment duration, dosage, and the site of application.
The main goal of photobanding is to achieve an isolating layer between the terminal nerve endings and the oral cavity. Photobanding with different laser regimens, notably erbium and diode lasers, provides immediate symptomatic relief independently of the parameters used by the operators.


References



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