Head Yuanshi Dian Therapy in Burning Mouth Syndrome
Head Yuanshi Dian Therapy in Burning Mouth Syndrome
Burning mouth syndrome is one of the most common oral mucosal diseases in clinic. It is a
 chronic pain syndrome with extensive burning pain of oral mucosa as its main symptoms. There
 are no pathological changes in oral mucosa and no characteristic histopathological changes.
 Patients often have accompanying symptoms such as depression and xerostomia. Although the
 patient does not have obvious oral lesions, the pain symptoms are more serious and the mental
 pressure is greater.

 BMS, as a complex clinical syndrome associated with multiple factors, mainly occurs in people
 aged 27-87, with an average age of 61. BMS is rare among people under 30 years old. BMS is
 predominant in women, the ratio of male to female is 1:5 to 1:7, the incidence is 0.7%-15%,
 and increases with age. Up to 90% of female patients are in perimenopausal period. Symptoms
 occur from 3 years before menopause to 12 years after menopause.

 The causes of BMS are complex, and the treatment is difficult, easy to relapse and
 protracted. Studies have confirmed that the occurrence and development of BMS are directly
 related to mental factors. Therefore, psychosocial factors are the most important pathogenic
 factors of BMS. If we intervene in these factors, it is hopeful to improve the curative
 effect of BMS.

 Traditional psychotherapy methods include drug treatment, psychotherapy, surgical treatment,
 traditional Chinese medicine treatment, etc. Drug treatment is mainly based on different
 types of mental and psychological diseases, choose different pharmacological effects of
 drugs, so as to effectively control the disease. However, these drugs are prone to adverse
 reactions such as sleepiness, weight gain, headache, physical weakness, etc. The basic
 principle of psychotherapy is to let patients fully expose symptoms, listen to their
 complaints patiently, carry out explanatory psychotherapy according to their medical history
 or take other psychological training, so as to relieve patients' mental stress and alleviate
 symptoms. But this method has a long course of treatment and needs the cooperation of the
 patients' family members; the basic principle of surgical treatment is to resect the
 corresponding areas of the brain or adopt endoscopy and micro-current to treat them, but the
 risks and injuries caused by the operation are greater, and the adverse reactions after the
 operation are larger; the treatment of traditional Chinese medicine needs a long course of
 treatment, and the treatment of some patients. The effect is not stable enough.

 The causes of BMS are complex, there is no objective disease in clinic, and the patients
 suffer from abnormal pain, but the treatment methods are not uniform, and the curative effect
 is not good, which makes the patients unable to get effective treatment in the early stage of
 the disease, and easy to relapse, resulting in the aggravation and development of BMS into
 intractable sensory abnormalities, and protracted! Literature reports confirm that the
 tri-drug of oryzanol-riboflavin-vitamin E (oryzanol-riboflavin-vitamin E) is a classic
 treatment for BMS and has been included in the classic book in China, Pharmacotherapy for
 oral mucosal disease . However, its long-term clinical application has found that its
 efficacy is unstable, and clinical symptoms after drug withdrawal. The symptoms are prone to
 recurrence or even aggravation. Therefore, it is necessary to use the classical program on
 the basis of a combination of interventions to promote the efficacy of stable and safe.

 Over the past two years, the investigators has treated nearly 100 cases of BMS with head
 yuanshi dian therapy, and achieved satisfactory results. It can obviously relieve burning
 pain of BMS oral mucosa, promote saliva secretion, improve dry mouth and bitter mouth, and
 improve sleep to a certain extent. However, due to the limited number of cases treated, the
 classification of BMS is not meticulous enough, and there are still vague areas in the
 classification of BMS, which affects the rigorous evaluation of the therapeutic effect of
 BMS.

 Therefore, the investigators propose a hypothesis: can the head yuanshi dian therapy be used
 as the main adjuvant therapy for BMS? By consulting Pubmed, OVID, CNKI, Wanfang and other
 major databases at home and abroad, the investigators found that there is no relevant report
 at home and abroad. In view of this, the investigators intend to design this randomized
 positive controlled clinical trial, using conventional valley-nucleus-E triple drug therapy
 as the positive control group, to observe the efficacy and safety of head yuanshi dian
 therapy for BMS, in order to find a safe and effective green non-invasive therapy,
 effectively alleviate or eliminate oral mucosal pain, dry mouth, etc.
2.1 Test Target

 To observe the efficacy and safety of head yuanshi dian therapy in the treatment of BMS.

 2.2 Case Collection 2.2.1 Diagnostic criteria

 1. Burning-like neuropathic pain occurs in the tongue or other parts of oral mucosa, which
 may be relieved or disappeared when attention is transferred.

 2. Most of them are accompanied by dry mouth, numbness, taste disorder, depression,
 insomnia and other emotional changes, neuropathological changes;

 3. Symptom changes may have special regularities and rhythms, such as mild morning symptoms
 and worsening afternoon symptoms; pain does not increase when eating or drinking water,
 and usually does not affect sleep; or persistent pain; or intermittent throughout the
 day;

 2.2.3 Exclusion criteria

 1. There are local stimulating factors that can cause burning pain in the mouth (including
 bad prosthesis, sharp cusp or ridge, complete denture, etc.).

 2. Patients with other serious oral mucosal diseases (including bullous diseases, allergic
 diseases, oral candidiasis, oral lichen planus, recurrent aphthous ulcer, etc.);

 2.2.4 Standards and procedures for discontinuation of trial/trial therapy When the following
 occurs, the trial can be stopped according to the judgement of the researcher, and the
 reasons for the discontinuation of the trial can be recorded in the case report form (CRF)
 and the original record. If the cause of adverse events leads to the discontinuation of the
 test, the relevant treatment should be carried out according to the adverse events.

 1. Misacceptance was found after enrollment;

 2. Those who received neurological, psychiatric drugs or other interventions during the
 trial;

 3. Those who did not use the test drug according to the doctor's advice or who were treated
 by the combination of internal and external heat source and push of the original point
 after admission into the group;

 2.3 randomization In this study, multi-center (Zhejiang University Second Hospital, Zhejiang
 Hospital of Traditional Chinese Medicine, Guiyang Stomatological Hospital, Guizhou, 3
 clinical research centers), non-inferior effect, 1:1 randomized controlled clinical trial
 were used. Random numbers generated by SPSS21.0 will be placed in sequentially coded, sealed,
 opaque envelopes. When the qualifications of the subjects were determined by the researchers,
 the envelopes were opened sequentially and the subjects were assigned to groups. The odd
 number represented the experimental group and the even number represented the control group.

 2.4 Measures to Reduce and Avoid Bias In order to reduce and avoid the bias of experimental
 conditions, the investigators should strictly group according to the random number of groups,
 and adopt the corresponding treatment plan. At the same time, in order to ensure the
 objectivity of the study group's evaluation of cases dropped and excluded, it is necessary to
 clarify the statistical treatment methods and evaluation criteria for cases dropped and
 excluded in the statistical analysis plan.

 2.5 Sample size calculation Referring to the previous study of this group, the difference and
 standard deviation of the mean between the two groups before treatment and after one month of
 treatment were used to calculate the sample size required for this study. Based on the visual
 analogue scale (VAS), the non-inferior boundary value was allowed to be 1 and the standard
 deviation was 1.3, and 22 persons were needed for each group (80% of the test efficiency and
 0.05 of the alpha). Taking into account the possibility of abscission, 48 cases were finally
 included.

 2.6 Researcher and patient training The main researcher receives relevant training in head
 yuanshi dian therapy, and can master the principle of the therapy and related matters needing
 attention, as well as the use of various psychological dosimeters. In addition, the main
 researcher trained the patients in this therapy so that they could take care of themselves at
 home.

 2.7 Basic information of subjects During the first and second visits, the investigators
 recorded the basic information of the subjects in the BMS Case Report Form: case number,
 random number, visiting date, name, sex, age, occupation, employment status, education level,
 contact mode, nationality, communication address, systemic disease, allergy history,
 medication history, and so on. Family history, female subjects recorded menstrual history,
 routine physical examination results, etc.

 2.8 Trial Groups and Treatment Programs 2.8.1 Treatment plan of control group Specific
 medicines and usage, course of treatment are as follows: oryzanol + vitamin B2 (riboflavin) +
 vitamin E, oryzanol tablets, oral, 10 mg/time, 3 times/day; vitamin B2 tablets, oral, 10
 mg/time, 3 times/day; vitamin E pills, oral, 100 mg/time, 1 time/day, 1 months as a course of
 treatment.

 2.8.2 Therapeutic regimen of experimental group On the basis of classical "Gu-Nucleus-E"
 triple drug therapy, the experimental group was treated with head yuanshi dian therapy twice
 a day for 1 months as a course of treatment.

 2.8.3 Specific operating procedure of head yuanshi dian therapy

 2.9 Evaluation Index of Therapeutic Effect After the first visit or passing the push maneuver
 retraining, participants will have a visit twice a week. The aim is to observe the efficacy
 and safety of the treatment. At the end of one week, two weeks, three weeks and one month of
 treatment, the researchers recorded the efficacy indicators of the patients. The
 immunoglobulin, hemorheology index, blood routine, ESR, CRP, blood lipid routine and changes
 were examined at the first diagnosis and at the end of treatment. At the end of the
 treatment, the drug was stopped, and the head Yuanshi Dian therapy was suspended in the
 experimental group. The patients were followed up one month after the treatment and three or
 six months after the treatment by telephone to observe the recurrence.

 2.10 Blind Assessment Each of the three centers has a researcher responsible for the
 treatment and interpretation of the subjects. The head of the research center trained the
 researcher to unify the standards. Three researchers were not involved in the evaluation of
 efficacy. Another researcher was responsible for recording pain and emotional nature and
 degree score, pain index, pain multi-dimensional characteristics score, depression index,
 Pittsburgh sleep quality index, Kupperman menopause score, dry mouth subjective symptoms
 questionnaire, saliva flow, and recording laboratory results, and collecting records. Data,
 analysis of efficacy, the researchers do not know the specific grouping, in order to minimize
 the subjective impact of the researchers on the test results.

 2.11 Safety Evaluation Index 2.11.1 Laboratory Indicators Two groups of subjects were
 required to provide the following examination reports within 12 months: blood routine, blood
 sugar, liver and kidney function, urine routine, abdominal ultrasonography, chest X-ray, sex
 hormone levels.

 2.11.2 Indicators of vital signs Including blood pressure and pulse. 2.11.3 Adverse reactions
 The subjects in the experimental group can inform the researchers of any discomfort and have
 the right to withdraw from the trial at any time when they are given the head yuanshi dian
 therapy. When the subjects in the control group were re-visited, the researchers asked if
 there were any adverse reactions during the medication process. If so, they should record in
 detail, including the number of adverse reactions (incidence), specific reactions,
 elimination and so on.
Inclusion Criteria:

 -  Persons aged 25-90;

 -  By inquiring the medical history in detail, BMS can be diagnosed if the clinical
 symptoms and signs do not conform to the clinical characteristics, and the medical
 history is more than 4 months.

 -  Burning pain and/or dry mouth in tongue or other parts of oral mucosa were the main
 clinical symptoms.

 -  Those with normal blood routine, blood sugar, liver and kidney function, urine
 routine, abdominal ultrasonography, chest X-ray and other basic physical examination
 items;

 -  Those who voluntarily participate in the experiment and sign the informed consent.

 Exclusion Criteria:

 -  There are local stimulating factors that can cause burning pain in the mouth;

 -  Patients with other serious oral mucosal diseases;

 -  Complicated with serious systemic diseases;

 -  Patients with mental disorders who take drugs routinely;

 -  Abnormal levels of sex hormones;

 -  Sjogren's syndrome.

 -  Possible drug-related xerostomia.

 -  Pregnant or lactating women;

 -  The patients'cognitive level was low and they could not understand and fill in the
 questionnaire correctly.

 -  Those who fail to comply with the doctor's advice or return to the doctor on time;

 -  Those who participated in clinical trials within 3 months.