Participants
Patients were recruited at Department of Oral Mucosal Diseases, Shanghai Ninth People’s Hospital during July of 2018 to June of 2019. The protocol was approved by Committee of Medical Ethics of the hospital (SH9H-2018-T18-2). The written informed consent was obtained from all patients. And, the trial was registered at Chinese Clinical Trial Registry (ChiCTR1800018834).
Inclusion criteria were as follows: (1) patients diagnosed as BMS in accordance with the International Association for the Study of Pain (IASP) [1] which characterized this syndrome as oral burning sensation without detectable organic lesion in oral cavity; (2) symptom of burning sensation only on the tongue; and (3) ability to complete the clinical trial.
Exclusion criteria: patients (1) with oral pain accompanied with detectable organic lesion in oral mucosa; (2) diagnosed as BMS but symptom of burning sensation was outside the tongue; (3) a history of psychosis; pregnancy or breast-feeding women; and (4) reluctance to give consent to participate.
Laboratory examinations were also performed including blood routine examination, blood glucose, serum iron, total iron binding capacity, iron saturation, vitamin B12, folic acid, 25-OH-D3, fungal culture, and allergic text. All enrolled BMS patients were arranged to have laboratory examinations at the end of treatment. Individuals with abnormal laboratory values were kept as “enrolled participant”, but modified diagnosis as “ secondary” BMS and treated accordingly.
Study design
Randomization
This randomized controlled trial (RCT) was single-blind, single-center, and parallel study. Patients were assigned to one of two groups by a computer program using simple sequentially numbered randomization table. The assignation number was uniformly kept in a sealed envelope until the moment of treatment. Participates were allowed to abandon the trial at any time if they no long wanted to receive therapy.
Sample size
Sample size was not estimated because of the lack of any studies using 1064nm Nd:YAG LLL treatment for BMS. Therefore, we arbitrarily decided to enrolled minimum 21 patients in each group for this pilot study.
Treatment modalities
Patients were randomly assigned to two groups: LLL group, the patients were irradiated with a Nd:YAG laser ( HSM-Ⅲ,Sichuan Aerospace Sid Control & Guide Co,. Ltd, China), according to the manufacturer’s instructions, and placebo group, the patients was treated under the same LLL instrument which was switched off.. The tongue was divided into 17 treatment regions (Fig. 1). The number of treatment region was depended on the extents of tongue affected. Before laser irradiation, the treatment areas were cleaned with normal saline and dried with gauze. The probe was applied vertically over mucosa at a distance of about 0.6cm where the irradiation area was 1cm2. The parameters of irradiation consisted of 100mW power, 3J/cm2 energy density, 10Hz, pulse mode and a 1064nm wavelength emission. Each patient underwent one laser irradiation session per week for 4 weeks.
Clinical assessment
Clinical assessment of subjective pain/burning, numbness and altered taste was performed using a visual analogue score (VAS), which consisting of a 10cm vertical line marked with 0 (absence of symptom) to 10 (the most severe symptom), right before each irradiation session and one week after last treatment.
The primary outcome of the study was the effectiveness of LLL treatment for pain/burning relief between baseline and the last session. The secondary outcomes were the effectiveness of LLL treatment in relief of numbness and altered taste. The effectiveness of LLL treatment was defined as the mean percentage of improvement in symptom and calculated using the following formula:
Effectiveness (%) = (VASbaseline – VASsession) x 100 / VASbaseline
Statistical analysis
Statistical analysis was performed using SPSS, version 24 (SPSS Inc, Chicago, Illinois). Basic variables including gender, systemic disease and menopause were analyzed using Chi-square test. Basic features including age and VAS of symptom were accessed by independent 2-sample t test. Non-normal distribution variable, diseases duration, was analyzed by Wilcoxon rank sum test. Comparison of VAS in either inter-group or intra-group for each session was analyzed by repeated-measures analysis of variance (ANOVA). Statistically significant deference was established as P < 0.05.