Laser - Revolutionizing The Treatment Of Recurrent Aphthous Stomatitis

Introduction

Oral ulceration is a break in the continuity of epithelium of oral tissues which frequently reveals nerve endings in the underlying layer i.e., lamina propria, leading to pain or soreness. Recurrent aphthous stomatitis (RAS), known as ‘canker sores’, is the most common cause of oral ulceration, affecting approximately 20% of the population. The phrase “aphthous” is acquired from the Greek word “aphtha,” which means ulceration. Stanley categorized RAS into three distinctive clinical types - firstly, Miculiz’s aphthae or minor RAS; secondly, major RAS which are also called as periadenitis mucosa necrotica recurrens or Sutton’s disease; and thirdly, herpetiform ulceration which is characterized by the presence of multiple ulcers, which may reach be up to 100 in number.¹ Of the three types, the smallest in size is the herpetiform ulcer, while the more common type is the minor aphthous or Mikulicz ulcer. This type appears as an elongated lesion with a crateriform base, surrounded by a white-grey pseudomembrane. The third form, known as "major aphthous" or "Sutton's ulcer," is less common compared to the other two.²

An aphthous ulcer is an oral condition of non-specific etiology. It is characterized by more than two bouts of occurrence of oral ulcers per year. It does not have association with any underlying systematic abnormality. No single factor or causal agent is responsible for RAS, but it could be attributed to an interaction of various cofactors of systemic or local nature or both. RAS is therefore a multifactorial condition, associated with numerous factors including hereditary factors, psychological and socioeconomical factors like stress, nutritional and immunological deficiencies and hormonal fluctuations.³ The management of RAS is aimed to provide symptomatic relief, including diminution in pain, time required for healing, and also decreasing number and size of the ulcer, and to increase disease free periods.⁴ The basis of treatment is centered on the suppression/reduction of the local immune response, thereby diminishing discomfort and preventing secondary infection.⁵ Considering the high frequency of RAS, associated discomfort, and the anti-inflammatory and reparative action of low-level laser therapy (LLLT), the aim of the study was to appraise and compare the clinical effects of administration of low-level laser and a topical corticosteroid on RAS.

Materials and Methods

The study was a randomized control study. It was conducted on 28 subjects who were selected randomly from a larger sample representative of people reporting in the outpatient department of Periodontics, Sri Guru Ram Das Institute of Dental Sciences and Research in Amritsar in the state of Punjab. Among 28 patients who began treatment, only 20 completed the study. The research protocol was submitted in the beginning to the institutional ethical committee. After ethical approval, all the subjects were verbally informed and a written approval was taken from all the subjects before their inclusion in the study. A detailed medical and dental history was recorded for each patient. The study was conducted in agreement with the principles embodied in the Helsinki Declaration of 1975, as revised in 2013. Patients with minor RAS only, having received other treatments for RAS without getting satisfactory results and who have not undergone treatment for any other systemic/oral disease in the previous three months were included in the study. Whereas patients with any systemic (endocrine–metabolic) disease, rheumatologic disease, hormone disorder, pregnancy, immunodeficiency, use of corticoid-based therapy, use of total or partial dentures, having restorations or teeth with sharp edges, use of orthodontic or other oral appliances and who did not participate daily in the evaluations were excluded.

The subjects who fulfilled the inclusion and exclusion criteria were randomly divided into two groups for study. Patients in Group I were treated with LLLT (Figure 1), while those in Group II were treated with topical corticosteroids (Figure 2). On their first visit, all patients underwent a clinical examination, including patient history and physical examination. They responded to specific inquiries about their RAS condition, including symptoms, number of lesions, average duration, frequency of episodes, potential triggering factors, and past treatments for aphthous ulcers.

Group I patients were treated with LLLT, while Group II received conventional treatment for recurring aphthous lesions using triamcinolone acetonide (Kenacort; orabase) three times per day. Patients were recalled on consecutive days for evaluation. Clinical evaluations were conducted during each session, and pain intensity was recorded before and after therapy.

Instrument used for pain-intensity assessment was ‘Visual Analogue Scale (VAS) / Graphic Rating Scale’. This scale consists of one straight line whose endpoints defines extreme limits such as ‘no pain at all’ and ‘pain as bad as it could be’.

Kenacort consists of 0.1% triamcinolone acetonide, a medium to high potency corticosteroid. It is a fluorinated prednisolone derivative and is considered an intermediate-acting glucocorticoid. It is an anti-inflammatory agent, aiding in diminishing the pain and inflammation.

The laser unit used was ‘AMD Diode LASER unit - Picasso lite 3.0’ (Figure 3). Output power of it was set at 0.5 W and wavelength used was of 810 nm. Before starting the procedure, the patient was made to sit at ease on the dental chair. All the necessary precautions were taken care of. Protective eyewear was worn by everyone in the dental set up, including the patient, the dentist, and the assistants present in the operatory during the procedure.

During each sitting, every patient was exposed to four sessions of low level laser therapy with each session lasting for about 45 seconds, conducted at a time interval of 30-60 seconds. Therefore, total application of laser was for three minutes. The mode of laser application was a non-contact mode achieved by keeping the laser tip at a distance of about 2-3 mm from the surface of the ulcer. The laser beam application was done in a constant sweeping and circular motion, covering the entire surface of the ulcer. Safety measures were taken to avert overheating of the ulcer’s surface and /or surrounding tissues.

Statistical analysis

The data were collected four times i.e., at baseline, day 1, day 2 and day 3 in both the groups. The results were then entered in a proforma prepared for the study. The recorded data were collected, compiled and subjected to statistical analysis to deduce the results. The analysis was performed with a Statistical Software Package for Social Sciences, version 17.0 (SPSS, Version 17.0, Inc, Chicago). Unpaired t-test was applied to evaluate the comparison between Group I and Group II at the end of treatment.

Results

• A total of 20 patients were included in the study, of which 12 were males and 8 were females. Eight out of ten patients in Group I reported absolute relief from pain instantly after the LLLT application.
• For appraisal of the decline in pain, the evaluation of mean reduction in VAS scores was done.
• Intra group comparison demonstrated a statistically highly significant reduction in both the tested parameters, both in Group I and Group II. 
• Intergroup comparisons revealed that the LLLT group experienced a statistically significant reduction in pain compared to the steroid group on days 1 and 2. But on 3rd day, statistically non-significant difference was observed between the pain perceived by both the groups (Table 1). 
• Unpaired t-test; *Statistically not significant; **Statistically highly significant
• Similarly, the mean reduction in ulcer size was measured to assess the effectiveness of laser therapy in decreasing lesion size.
• The LLLT group had a statistically significant reduction in pain when compared to the steroid group, but a non-significant difference was seen between the efficacies of two agents in reducing the size of the lesion (Table 2).

Discussion

RAS is one of the most painful inflammatory ulcerative conditions affecting oral mucosa characterized by pain experienced during various daily activities like eating, swallowing, and speaking.¹ The foremost concern in the management of RAS is achieving reduction in pain and size of the ulcers.⁵ Numerous treatment modalities being used include steroids, mouthwashes, etc. However, all of these are associated with multiple side effects, with a requirement of patient compliance, and are also expensive. In this context, LLLT can be considered advantageous as it not only provides instantaneous pain relief, but is also considered cost-effective. It is also time saving as the effects are apparent in a single sitting.¹

The present study results confirmed that the extent of decline in the intensity of pain was higher with LLLT as compared to triamcinolone acetonide.

Biological rationale of using LLLT

The biological mechanism of pain relief as an outcome of laser therapy is a theme of meticulous research.

Anti-inflammatory and pain-relieving action

The proposed mechanisms of anti-inflammatory and pain-relieving actions of LLLT are as follows.

• LLLT causes modulation of nociceptors through modification in the procedure of transmission of nerve impulses and by the secretion of endorphins and enkephalins.⁶ 
• It inhibits the production of chemical mediators like prostaglandin E2 and interleukin-1 beta which aids in alleviating the pain (PG is responsible for enhancing pain perception by increasing the sensitization of the receptors and by lowering their thresholds).⁷ 
• Another mode of pain relief with LLLT application is linked to amplified ATP production in the neuronal mitochondria. Reduced ATP synthesis is responsible for mild depolarization resulting in decreased threshold required for triggering an action potential. Therefore heightened ATP synthesis caused by LLLT brings about hyperpolarization and thus causes obstruction of stimuli, thereby dwindling the initiation of pain stimuli.⁸

1. The surge in ATP synthesis by LLLT is fundamentally reliant upon the assimilation of red and also near infrared wavelengths in photoreceptors present inside the sub-cellular mitochondrial apparatus, distinctively in the electron transport (respiratory) chain.⁹
2. Consequently, there is simulation of the respiratory chain as well as oxidation of NADH pool for short-time.
3. The resulting spur in oxidative phosphorylation alters the redox potential of the both mitochondria as well as cytoplasm of the cell, which boosts various process including the delivery of ATP, electrical potential of the membrane of mitochondria, alkalization of cytoplasm, nucleic acid synthesis.¹⁰

• LLLT also affects lymphocyte metabolism, including the activation of suppressor T lymphocytes. It interferes with the secretion of histamine, kinins, and tumor necrosis factor, all of which reduce the inflammatory response and subsequently decrease pain.⁵

Effect on healing

1. Healing is the key characteristic of LLLT which is essentially related to three principal factors.
2. Firstly, the laser therapy augments the ATP production intensifying both the mitotic activity and protein synthesis by mitochondria, which eventually results in better tissue regeneration and a rapid repair process. 
3. Secondly, the multiplication of cell is accelerated by the stimulation of microcirculation, resulting in the amplification of deliverance of nutritional elements, coupled with the amplified speed of mitosis. 
4. Lastly, LLLT causes neoangiogenesis from the preexisting vessels.³
5. When delivered in appropriate amounts, photon’s energy in LLLT is transformed into various effects including photochemical, photophysical and photobiological.¹¹
6. This results in simulation of lymphocytes, mast cells and heightened ATP synthesis.
7. Also proliferation of diverse types of cells like fibroblasts and macrophages occurs.
8. All these collective factors encourage anti-inflammatory and biostimulatory effects which accentuates the wound healing.¹²
9. The mast cell activation simulates pro-inflammatory cytokines’ release, which heightens the local leukocytic infiltration of tissues.
10. Because mast cells take part in key roles of leukocyte functions, any modulation in their activity can substantially affect wound healing in the oral cavity.¹³

• LLLT amplifies processes like proliferation, maturation and locomotion of fibroblasts and causes a spike in the formation of basic fibroblast growth factor.
• It diminishes synthesis of prostaglandin E2 (PGE2).¹⁴ These effects on fibroblasts may promote wound healing.
• However, elevated amount of laser power may restrain not only the fibroblast proliferation but also the production of basic fibroblast growth factor.¹⁵ Hence, it is very important to sustain an optimal dose of LLLT.

The results of the current study demonstrated that administration of LLLT, which is extensively used in managing inflammatory diseases is not an inhibitor, but owing to its modulating action, was effective in curing aphthous ulcers. The results of the present study support the theory that LLLT aids in pain control and promotes wound healing. Results of the present study are in harmony with those reported by Albrektson et al. (2014) which revealed that LLLT application provided a notable analgesic effect in the healing of acute minor aphthous ulcers in comparison to the placebo group.¹⁶ It also radically reduced pain levels experienced during daily activities like eating, drinking, and brushing teeth. Similarly, a study by Aggarwal et al. (2014) demonstrated that LLLT is effective in reducing pain and accelerating the healing time of aphthous ulcers.⁴ Results of the study conducted by De Souza et al. (2010) revealed a decline in pain in the first appointment after LLLT treatment, and an absolute decrease in the lesion size noticed after four days in 75% of the patients.⁵ Khademi et al. (2009) reported similar benefits including prompt healing and diminution in pain.

Though cases in the present study have been treated with semiconductor diode laser also referred to as “cold” or “soft” laser, the “hard” or “hot” surgical lasers (like CO2, Nd: YAG) are also used for providing LLLT. Zand et al. (2009) used a low intensity, non thermal, solitary session of CO2 laser and Iris Brader (2008) used Nd: YAG laser in a non-contact mode for curing minor RAS^18,19. Both reported striking and instantaneous pain reduction in the patients following irradiation. However, diode lasers have an edge over their high powered “hard” surgical laser counterparts, as they are safe, do not cause any thermal damage to hard tissues, are compact, cost-effective, and have incredible electrical and optical efficiencies.¹³

Certainly, our study had a few limitations. Nonetheless, we believe these findings are significant and support the use of LLLT as a therapeutic tool for RAS. However, further research with varying parameters (such as energy density and power) is necessary to establish an optimal protocol for using LLLT in RAS treatment.

Conclusion

In the current study, using LLLT to treat minor recurrent aphthous stomatitis (RAS) resulted in immediate pain relief. As medication was not necessary, their side effects and possibility of over dosage could be prevented. Consequently, it can be concluded that LLLT is a clinically secure and valuable treatment modality for managing minor RAS.

Conflict of Interest

Nil