Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

OBJECTIVE: Photobiomodulation therapy is recommended by multiple international societies for managing oral mucositis. These recommendations are based on extensive evidence. However, the search for an optimal photobiomodulation protocol continues. This mapping review focuses on a novel aspect of photobiomodulation therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about oral mucositis, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to oral mucositis management. The scientific database used was PubMed. CONCLUSION: Whereas most of the randomized controlled trials about photobiomodulation therapy for oral mucositis and other ulcerative oral diseases reported delayed pain relief, certain photobiomodulation therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive photobiomodulation therapy, in which photobiomodulation therapy is delivered early in the development of oral mucositis throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. Photobiomodulation therapy, as a powerful nonpharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from oral mucositis and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM).

OBJECTIVES: The effect of photobiomodulation (PBM) treatment on wound healing and macrophage polarization was investigated in vivo. Animal models of oral ulcers were simulated through chemically induced oral ulcers in rats. MATERIALS AND METHODS: PBM treatment using an infrared pulsed laser was used to treat oral ulcers in the animal models. Twelve Sprague-Dawley rats were randomly divided into four groups depending on set absorbed energy: Group 1 (control), Group 2 (30 J), Group 3 (60 J), and Group 4 (100 J). Laser treatment was performed every other day for 8 days after ulcer confirmation. Parameters used were as follows: wavelength 808 nm, power output 50 mW, spot size 10 mm, frequency 10 Hz, and pulse duration 1 millisecond. Ulcers were measured to determine the effect of the treatments over time. Histology, immunostaining, and real-time polymerase chain reaction analyses were performed to evaluate the effect of PBM treatment on macrophage-related (IL-6/IL-10) and wound-healing-related (TNF-α/TGF-ß/MMP-2) cytokine expression. RESULTS: Histological examinations indicate that the PBM treatment stimulated a higher level of wound recovery after 8 days of treatment at 60 J absorbed energy compared to other treatment groups. Analyses of relative gene expression of proinflammatory, anti-inflammatory, and tissue remodeling cytokines indicate that the macrophages in the tissue samples were predominantly characterized as M2 subtypes (alternatively activated), which possibly accounts for the accelerated tissue repair in the animal model of oral ulcer. CONCLUSION: This preliminary study stands as a proof of concept regarding the potential use of infrared laser PBM treatment for oral ulcers which have not been previously investigated upon. PBM treatment affects macrophage polarization and enhances wound healing. Further experimentation will be conducted to expand the understanding of how PBM treatment affects the healing mechanism of ulcers.

Transoral Low-Level Laser Therapy Via a Cylindrical Device to Treat Oral Ulcers in a Rodent Model.

BACKGROUND AND OBJECTIVE: Various clinical and animal studies have applied low-level laser therapy (LLLT) to treat oral ulcers. However, most previous studies applied lasers with small pinpoint irradiation, which required multiple laser irradiations to cover the complete extent of the ulcer. The objective of this study was to evaluate the effect of LLLT using a 635 nm diode laser via a transoral device to cover the whole lesion on oral ulcers in an animal model. STUDY DESIGN/MATERIALS AND METHODS: An animal model of oral ulcers was developed with a 6 mm skin punch in the right buccal mucosa of Wistar rats (males, body weight 200-250 g). Three days after the mucosal injury, LLLT (spot size 2 cm2 ) was conducted once a day for 5 days. Twenty-eight rats were randomly assigned into four groups according to energy density (control group, 5, 20, 75 J/cm2 ). The size of the ulcers was measured and histologic analysis were performed ten days after the initial mucosal injury. RESULTS: The mean size of the oral ulcers was significantly smaller in rats treated with an energy density of 20 J/cm2 than that of any other group (control group or energy densities of 5 or 75 J/cm2 ). The irradiation of oral ulcers with an energy density of 20 J/cm2 accelerated the oral mucosa wound healing process and decreased inflammation and granulation tissue, resulting in good reepithelization. However, the histologic outcomes of rats irradiated with energy densities of 5 or 75 J/cm2 were comparable with those of the control group. CONCLUSION: LLLT using a 635 nm diode laser for oral ulcers with a transoral cylindrical device for wide light distribution may accelerate the wound healing process. LLLT with large-surface irradiation may be a substitute for previous LLLT for oral mucosal lesions conducted in a punctuate manner. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Photobiomodulation therapy: management of mucosal necrosis of the oropharynx in previously treated head and neck cancer patients.

Necrosis of the oral mucosa following head and neck cancer radiation therapy presents considerable clinical management challenges. We report three cases of symptomatic persisting oral ulcerations where the addition of photobiomodulation therapy resulted in a rapid resolution of the oral lesions and in patient symptoms. These cases suggest that photobiomodulation may represent an adjunct to care of these difficult to manage complications in oncology.

Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats.

The aim of the present study was to evaluate the effects of photobiomodulation (PBM) on cytokine levels and angiogenesis during oral wound healing. Ulcers were made on the dorsum of the tongue in 48 Wistar rats. Irradiation with an indium-gallium-aluminum-phosphide (InGaAlP) laser (660 nm; output power, 40 mW; spot size, 0.04 cm(2)) was performed once a day on two points of the ulcer for 14 days. Two different energy densities were used: 4 J/cm(2) (energy per point 0.16 J, total energy 0.32 J) and 20 J/cm(2) (energy per point 0.8 J, total energy 1.6 J). Tissue levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were investigated by enzyme-linked immunosorbent assay (ELISA). Image analysis of CD31-immunostained sections was used to investigate microvessel density (MVD). PBM increased the tissue levels of IL-1ß at the early stage of oral wound healing (p < 0.01) and increased the tissue levels of TNF-α during all stages of oral wound healing (p < 0.05). PBM at a dose of 4 J/cm(2) produced more significant results regarding cytokine modulation and was associated with higher MVD at day 5. Collectively, these findings indicate that cytokine modulation and increased angiogenesis are among the basic mechanisms whereby PBM improves oral wound repair.

Clinical evaluation of the Er,Cr:YSGG Laser therapy in the treatment of denture-related traumatic ulcerations: a randomized controlled clinical study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of Er,Cr:YSGG laser irradiation in reducing pain and on healing rate of traumatic ulcerations (TU) during a 2-week period after placement of new complete dentures. BACKGROUND DATA: Denture-related TU are painful, and result in patient discomfort. Lasers are used in the treatment of different kinds of mucosal lesions; however, there are no published data available concerning the clinical outcome of the use of laser therapy in the treatment of TU. MATERIALS AND METHODS: Thirty edentulous patients with newly fabricated complete dentures who subsequently developed one or more pairs of TU participated in this study. For each patient, ulcerations were randomly assigned to the test and control groups. In the test group, ulcerations were irradiated with Er,Cr:YSGG laser. In the control group, the same laser without laser emission was used. Pain was assessed with a visual analog scale (VAS). Healing of ulcerations (HU) was graded by a clinician. RESULTS: In the test group, laser irradiation provided significantly reduced pain immediately after treatment, and provided a significant healing effect 1 day after treatment, and these effects were maintained throughout the study. In the control group, baseline VAS scores were not statistically significant at baseline and 1 day after treatment, and HU scores were statistically significant 3, 7, and 14 days after treatment. Intergroup comparisons revealed that the differences in VAS and HU scores were statistically significant for all time periods after treatment, except for day 14. CONCLUSIONS: Based on these findings, it may be concluded that Er,Cr:YSGG laser is effective in the treatment of TU.

Effect of laser (λ 660 nm) and LED (λ 630 nm) photobiomodulation on formocresol-induced oral ulcers: a clinical and histological study on rodents.

The aim of this study was to evaluate, clinically and histologically, the influence of laser and LED photobiomodulation in the healing of formocresol-induced oral mucosa ulcers of rats. We used 60 Wistar rats in which oral ulcers were induced on the gingiva of the lower incisors. Forty-eight hours after inducing the ulcers, the animals were divided into three groups: laser, LED, and untreated. Animals from the laser group received irradiation with GaAlAs, 660 nm, CW, 40 mW, φ 4 mm(2), 4.8 J/cm(2). Animals from the LED group received irradiation with InGaAIP, 630 nm, 150 mW, 4.8 J/cm(2), 0.8 cm spot. Forty-eight hours after oral ulcer induction, both irradiations were applied in a punctuate manner in the center of the ulcer at 48-h interval until the end of the experimental period. The animals were killed at 3, 5, 7, and 11 days after day 0. The results of the clinical evaluation showed that the laser and LED phototherapies were able to accelerate the healing of formocresol-induced oral ulcers, which occurred first in the laser group (ANOVA, p < 0.05). Histologically, there was a slight variation between LED and laser therapy; therefore, the laser group proved to be effective in accelerating wound healing, especially at 5 days, whereas the LED group was more effective at the end of the experimental period. It was concluded that laser and LED photobiomodulation were effective in accelerating the healing of formocresol-induced oral ulcers in both clinical and histological aspects.

Temperature measurement and Hsp47 immunoexpression in oral ulcers irradiated with defocused high-energy diode laser.

UNLABELLED: Heat shock proteins (HSPs) are conservative protective proteins responsible for protein integrity during transcription in the cell under stress. Hsp47 is one of the most important chaperonins for collagen synthesis and release, and is up-regulated during wound repair. The aim of this study was to verify whether defocused high-energy diode laser (DDL) causes sufficient increase in local temperature to cause Hsp47 up-regulation during repair of oral ulcers. Chemically-induced ulcers in the rat tongue, and non-ulcerated tongue mucosa were irradiated using a high energy diode laser (non-contact - 4mm from surface, 500 mW, 10 Hz for 40s, energy density 80 J/cm(2), fixed ulcer area of 0.25 cm(2)). Afterwards the specimens were submitted to immunohistochemical test for Hsp47. Temperature oscillation during DDL irradiation was also measured using a thermographic camera. Irradiated specimens exhibited transient mild increase in local temperature and significant up-regulation of Hsp47 in the mucosa from the superficial region (p=0.035) to 1.7 mm deep (p=0.049). In the deepest region of the mucosa Hsp47 was up-regulated only in ulcerated specimens mainly at 24h (p=0.049) and 72 h (p=0.029) after ulcer induction. CONCLUSION: DDL increases local temperature and Hsp47 expression, which may contribute to wound repair by improvement collagen synthesis and release.

Low level laser therapy in oral mucositis: a pilot study.

AIM: The goal of this pilot study was to investigate the capacity of pain relief and wound healing of low level laser therapy (LLLT) in chemotherapy-induced oral mucositis (OM) in a paediatric oncology population group. STUDY DESIGN AND METHODS: 16 children (mean age 9.4 years) from the Gent University Hospital - Department Paediatric Oncology/haematology, suffering from chemotherapy-induced OM were selected. During clinical investigations, the OM grade was assessed using the WHO classification. All children were treated using a GaAlAs diode laser with 830 nm wavelength and a potency of 150 mW. The energy released was adapted according to the severity of the OM lesions. The same protocol was repeated every 48 hrs until healing of each lesion occurred. Subjective pain was monitored before and immediately after treatment by an appropriate pain scale and functional impairment was recorded. At each visit, related blood cell counts were recorded. RESULTS: After 12 mths, records were evaluated and information about treatment sequence, treatment sessions and frequencies related to the pain sensation and comfort were registered. Immediately after beaming the OM, pain relief was noticed. Depending on the severity of OM, on average, 2.5 treatments per lesion in a period of 1 week were sufficient to heal a mucositis lesion. CONCLUSIONS: LLLT, one of the most recent and promising treatment therapies, has been shown to reduce the severity and duration of mucositis and to relieve pain significantly. In the present study similar effects were obtained with the GaAlAs 830nm diode laser. It became clear that using the latter diode device, new guidelines could be developed as a function of the WHO-OM grades i.e. the lower the grade, the less energy needed. Immediate pain relief and improved wound healing resolved functional impairment that was obtained in all cases.

Chemotherapy-induced oral mucositis in a patient with acute lymphoblastic leukaemia.

BACKGROUND: Oral mucositis is the main complication of chemotherapy and radiotherapy used in the treatment of cancer. Phototherapy has proven effective in the treatment of mucositis, as it accelerates the tissue healing process and has both analgesic and anti-inflammatory properties. CASE REPORT: This paper reports the case of a paediatric patient with oral mucositis stemming from chemotherapy employed for the treatment of acute lymphoblastic leukaemia. TREATMENT: The lesions were treated daily with a light-emitting diode (LED). FOLLOWUP: Remission of the lesions occurred after 10 days of treatment. CONCLUSIONS: LED was effective in the treatment of mucositis, as it diminished pain symptoms and accelerated the tissue repair process.

Use of laser phototherapy on a delayed wound healing of oral mucosa previously submitted to radiotherapy: case report.

Radiotherapy produces both acute and delayed effects on mucosal tissues, disturbing their healing. This report shows a successful treatment with laser phototherapy (LPT) on a delayed wound healing in oral mucosa previously submitted to radiotherapy with a follow up of 3 years. A 47-year-old patient treated 6 months earlier for tongue squamous cell carcinoma by surgery and radiotherapy presented with a mass in the operated area. Biopsy showed chronic inflammatory infiltrate around a residual polyglactin suture. After 2 months there was a painful mucosal dehiscence on the biopsy site. LPT was performed using a semiconductor laser with 660-nm wavelength (InGaAlP) and spot size of 0·04 cm(2) . The parameters applied were 40 mW, 4 Jcm(2) /point, 0·16 J/point, 2·4 J/session. The irradiation was performed punctually, through contact mode in 15 points (4 seconds/point), on top of and around the lesion, during ten sessions. The wound healed completely after ten sessions. This treatment proved to be conservative and effective, inducing healing of a chronic wound in a tissue previously submitted to radiotherapy.

Improvement in quality of life of an oncological patient by laser phototherapy.

OBJECTIVE AND BACKGROUND DATA: Common side effects of radiotherapy (RT) to the head and neck include oral mucositis, xerostomia, and severe pain. The aim of this study is to report improvement in the quality of life of an oncological patient by laser phototherapy (LPT). CLINICAL CASE AND LASER PHOTOTHERAPY PROTOCOL: The patient, a 15-year-old girl diagnosed with mucoepidermoid carcinoma, underwent surgical excision of a tumor of the left palatomaxilla. After that, she was subjected to 35 sessions of RT (2 Gy/d). Clinical examination revealed the spread of severe ulcerations to the jugal mucosa, gums, lips, hard palate, and tongue (WHO mucositis score 3). She had difficulty in moving her tongue and she was unable to eat any solid food. Oral hygiene orientation and LPT were performed throughout all RT sessions. A continuous diode laser, 660 nm, 40 mW, 6 J/cm(2), 0.24 J per point in contact mode, with spot size of 0.04 cm(2) was used in the entire oral cavity. A high-power diode laser at 1 W, 10 sec per cm of mucositis, approximately 10 J/cm(2), was used in defocused mode only on ulcerative lesions. After the first laser irradiation session, decreases in pain and xerostomia were reported; however, a more significant improvement was seen after five sessions. At that point although the mucositis score was still 2, the patient reported that she was free of pain, and consequently a palatine plate could be made to rehabilitate the entire surgical area. Seventeen laser irradiation sessions were necessary to eliminate all oral mucositis lesions. CONCLUSION: Normal oral function and consequent improvements in the quality of life of this oncologic patient were observed with LPT.

Macroscopic and microscopic effects of GaAIAs diode laser and dexamethasone therapies on oral mucositis induced by fluorouracil in rats.

PURPOSE: To present an animal model for mucositis induced by fluorouracil in rats, and test two therapeutic options, the GaAIAs laser and topical dexamethasone, analysing them with regard to the quality and quantity of tissue alterations and comparing them with the phases of mucositis. MATERIALS AND METHODS: Forty-five Wistar rats (250 g) were treated with fluorouracil (60 mg/kg) and, in order to mimic the clinical effect of chronic irritation, the palatal mucosa was irritated by superficial scratching with an 18-gauge needle. When all of the rats presented oral ulcers of mucositis, they were randomly allocated to one of three groups: group I was treated with laser (GaAIAs), group II was treated with topical dexamethasone, and group III was not treated. Excisional biopsies of the palatal mucosa were then performed, and the rats were killed. Tissue sections were stained with haematoxylin and eosin for morphological analyses, and with toluidine blue for mast-cell counts. RESULTS: Group I specimens showed higher prevalence of ulcers, bacterial biofilm, necrosis and vascularisation, while group II specimens showed higher prevalance of granulation tissue formation. There were no significant statistical differences in the numbers of mast cells and epithelial thickness between groups. CONCLUSION: For the present model of mucositis, rats with palatal mucositis treated with laser (GaAIAs) showed characteristics compatible with the ulcerative phase of oral mucositis, and rats treated with topical dexamethasone showed characteristics compatible with the healing phase of mucositis. Topical dexamethasone was more efficient in the treatment of rats' oral mucositis than the laser.

Low-level-laser therapy as an alternative treatment for primary herpes simplex infection: a case report.

Gingivostomatitis is the most common primary and symptomatic clinical manifestation of HSV-1 infection. Painful oral lesions appear as ulcerative erosions on the gingiva, palate, buccal mucosa, and tongue, leading to eating and drinking difficulties with an evolution between 10-14 days. This paper describes a case of a 19-month-old boy with severe painful Gingivostomatitis lesions. Low level laser therapy (LLLT) was used with an immediate outcome.

CO2-laser treatment of ulcerative lesions.

This article reports the successful use in our clinic of CO(2)-laser to reduce severe pain in the treatment of oral aphthosis. The patients, presenting stress-related, chemoradiotherapy-induced, and immuno-related oral aphthosis, reported immediate pain relief and rapid recovery. Treatment technique and laser parameters are described.

Irradiation of histiocytosis X confined to the oral mucosa.

BACKGROUND: Histiocytosis X is a rare granulomatous disease and it is still under debate as to whether this disease has to be counted among malignant tumors or benign immunologic lesions. The typical localization is confined to the bone. In rare cases histiocytosis X may be localized in the oropharyngeal mucosa. PATIENTS AND METHODS: We report about a case of a 75-year-old woman presenting with histiocytosis X lesions solely located in the oral cavity. A total dose of 19.5 Gy was administered without any side effects. RESULTS: Two weeks after completion of irradiation a rapid regression of mucosal ulcerations and improvement of symptoms occurred. In a follow-up of 24 months the patient is still in complete remission observed. CONCLUSION: Review of the literature revealed only casuistic reports about solitary lesions of histiocytosis X without bone involvement in the adulthood. External beam radiotherapy with total doses between 10 and 20 Gy seems to be effective for local control of this disease.