Developing a research diagnostic criteria for burning mouth syndrome: Results from an international Delphi process.

OBJECTIVE: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. DESIGN: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. RESULTS: The definition of BMS was agreed to be 'an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation'. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. CONCLUSION: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

Symptom severity in burning mouth syndrome associates with psychological factors.

Burning mouth syndrome (BMS) patients are psychologically distressed, but whether this associates with symptom severity is unclear. The aim was to investigate the association of psychological factors with pain intensity and interference in BMS. Fifty-two women (mean age 63.1, SD 10.9) with BMS participated. Pain intensity and interference data were collected using 2-week pain diaries. Psychological factors were evaluated using Depression Scale (DEPS), Pain Anxiety Symptom Scale (PASS) and Pain Vigilance and Awareness Questionnaire (PVAQ). The local ethical committee approved the study. Patients were divided into groups based on pain severity distribution tertiles: low intensity (NRS ≤ 3.7) or interference (NRS ≤ 2.9) (tertiles 1-2, n = 35) and moderate to intense intensity (NRS > 3.7) or interference (>2.9) (tertile 3, n = 17). T test, Wilcoxon's test and Pearson's correlation coefficient were used in the analyses. Patients in the highest intensity and interference tertiles reported more depression (P = .0247 and P = .0169) and pain anxiety symptoms (P = .0359 and P = .0293), and were more preoccupied with pain (P = .0004 and P = .0003) than patients in the low intensity and interference groups. The score of the pain vigilance questionnaire correlated significantly with pain intensity (r = .366, P = .009) and interference (r = .482, P = .009). Depression (r = .399, P = .003) and pain anxiety symptoms (r = .452, P = .001) correlated with pain interference. Symptom severity in BMS associates with symptoms of psychological distress emphasising the need to develop multidimensional diagnostics for the assessment of BMS pain.

Validation of diagnostic methods for traumatic sensory neuropathy and neuropathic pain.

INTRODUCTION: We evaluated diagnostic value of sensory tests during recovery from iatrogenic sensory neuropathy using intraoperatively verified nerve injury with subjective symptoms as gold standard. METHODS: Inferior alveolar nerves were monitored neurophysiologically throughout mandibular osteotomy in 19 patients. Sensory disturbance was registered and sensation tested using clinical and quantitative sensory (QST) and neurophysiologic tests postoperatively at 1, 3, 6, and 12 months. Sensitivity, specificity, and predictive values were calculated for all tests. RESULTS: The sensitivity of clinical tests was at best 37%, with 100% specificity, but they lost diagnostic value at chronic stages. Best diagnostic accuracy (highest combination of sensitivity and specificity) at different time points was achieved by combining neurophysiologic and thermal QST or tactile and thermal QST. The single most accurate test was sensory neurography. CONCLUSIONS: Neurography or combinations of neurophysiologic and quantitative tests enables most reliable early and late diagnosis. Clinical sensory examination is inadequate for accurate diagnosis. Muscle Nerve 59:342-347, 2019.

World Workshop on Oral Medicine VII: Burning mouth syndrome: A systematic review of disease definitions and diagnostic criteria utilized in randomized clinical trials.

OBJECTIVE: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). METHODS: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. RESULTS: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. CONCLUSIONS: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

World Workshop in Oral Medicine VII: Reporting of IMMPACT-recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review.

OBJECTIVES: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). METHODS: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. RESULTS: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. CONCLUSIONS: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

Painful temporomandibular disorders (TMD) and comorbidities in primary care: associations with pain-related disability.

Objective: We studied whether primary care temporomandibular disorder (TMD) patients reporting different levels of pain-related disability differ in terms of comorbid pains, general health conditions and quality of life.Material and methods: Consecutive TMD pain patients (n = 399) seeking treatment in primary care completed a questionnaire on comorbid pains and their interference and the Finnish version of the RAND-36-item quality of life questionnaire. Medical diagnoses confirmed by doctors were recorded. The patients were classified according to the Graded Chronic Pain Scale (GCPS) of the Research Diagnostic Criteria for TMD (RDC/TMD). The patients were classified: no disability group (0 disability points), low disability group (1-2 disability points) and high disability group (3-6 disability points).Results: Compared to patients in the no-disability group, patients in the high- and low-disability groups reported more comorbid pain conditions (p < .001), and experienced these as more intense and interfering more with daily life (p < .05). Patients in the high-disability group reported more general health-related medical diagnoses than patients in the no-disability group (p < .05). Furthermore, patients with low or high pain-related disability indicated poorer quality of life in all RAND-36 subscales than those with no disability (p < .05).Conclusions: The findings suggest that GCPS-related disability scoring can be used as a simple screening instrument to identify TMD patients with different degrees of health burdens.

Interventions for treating burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a term used for oral mucosal pain (burning pain or discomfort in the tongue, lips or entire oral cavity) without identifiable cause. General population prevalence varies from 0.1% to 3.9%. Many BMS patients indicate anxiety, depression, personality disorders and impaired quality of life (QoL). This review updates the previous versions published in 2000 and 2005. OBJECTIVES: To determine the effectiveness and safety of any intervention versus placebo for symptom relief and changes in QoL, taste, and feeling of dryness in people with BMS. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11) in the Cochrane Library (searched 31 December 2015), MEDLINE Ovid (1946 to 31 December 2015), and Embase Ovid (1980 to 31 December 2015). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any treatment against placebo in people with BMS. The primary outcomes were symptom relief (pain/burning) and change in QoL. Secondary outcomes included change in taste, feeling of dryness, and adverse effects. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Outcome data were analysed as short-term (up to three months) or long-term (three to six months). MAIN RESULTS: We included 23 RCTs (1121 analysed participants; 83% female). Interventions were categorised as: antidepressants and antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical barriers, psychological therapies, and topical treatments.Only one RCT was assessed at low risk of bias overall, four RCTs' risk of bias was unclear, and 18 studies were at high risk of bias. Overall quality of the evidence for effectiveness was very low for all interventions and all outcomes.Twenty-one RCTs assessed short-term symptom relief. There is very low-quality evidence of benefit from electromagnetic radiation (one RCT, 58 participants), topical benzodiazepines (two RCTs, 111 participants), physical barriers (one RCT, 50 participants), and anticonvulsants (one RCT, 100 participants). We found insufficient/contradictory evidence regarding the effectiveness of antidepressants, cholinergics, systemic benzodiazepines, dietary supplements or topical treatments. No RCT assessing psychological therapies evaluated short-term symptom relief.Four studies assessed long-term symptom relief. There is very low-quality evidence of a benefit from psychological therapies (one RCT, 30 participants), capsaicin oral rinse (topical treatment) (one RCT, 18 participants), and topical benzodiazepines (one RCT, 66 participants). We found no evidence of a difference for dietary supplements or lactoperoxidase oral rinse. No studies assessing antidepressants, anticonvulsants, cholinergics, electromagnetic radiation or physical barriers evaluated long-term symptom relief.Short-term change in QoL was assessed by seven studies (none long-term).The quality of evidence was very low. A benefit was found for electromagnetic radiation (one RCT, 58 participants), however findings were inconclusive for antidepressants, benzodiazepines, dietary supplements and physical barriers.Secondary outcomes (change in taste and feeling of dryness) were only assessed short-term, and the findings for both were also inconclusive.With regard to adverse effects, there is very low-quality evidence that antidepressants increase dizziness and drowsiness (one RCT, 37 participants), and that alpha lipoic acid increased headache (two RCTs, 118 participants) and gastrointestinal complaints (3 RCTs, 138 participants). We found insufficient/contradictory evidence regarding adverse events for anticonvulsants or benzodiazepines. Adverse events were poorly reported or unreported for cholinergics, electromagnetic radiation, and psychological therapies. No adverse events occurred from physical barriers or topical therapy use. AUTHORS' CONCLUSIONS: Given BMS' potentially disabling nature, the need to identify effective modes of treatment for sufferers is vital. Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective. Future studies are encouraged to assess the role of treatments used in other neuropathic pain conditions and psychological therapies in the treatment of BMS.

Pain and pain behavior in burning mouth syndrome: a pain diary study.

AIMS: To characterize pain related to primary burning mouth syndrome (BMS) in terms of intensity, interference, and distress caused by the pain, as well as factors influencing the pain across a period of 2 weeks, and to study the use of coping and management strategies on a daily basis. METHODS: Fifty-two female patients with primary BMS completed a 2-week pain diary. Pain intensity, interference, distress, and mood on a 0 to 10 numeric rating scale (NRS), as well as pain amplifying and alleviating factors, were recorded three times a day. The use of treatments (medication or other means) and coping strategies were recorded at the end of each day. Coefficient of variation, repeated measures analysis of variance, and correlative methods were used to assess the between- and within-subject variation, pain patterns, and associations between various pain scores. RESULTS: The overall mean pain intensity score of the 14 diary days was 3.1 (SD: 1.7); there was considerable variation in pain intensity between patients. Most patients experienced intermittent pain. On average, pain intensity increased from the morning to the evening. Intercorrelations between pain intensity, interference, distress, and mood were high, varying between rs = .75 and rs = .93 (P < .001). Pungent or hot food or beverages, stress, and tiredness were the most frequently mentioned pain-amplifying factors. The corresponding pain-alleviating factors were eating, sucking pastilles, drinking cold beverages, and relaxation. Thirty (58%) patients used pain medication and 35% reported using other means to alleviate their BMS pain. There was large variation in the use of coping strategies -between subjects. CONCLUSION: There were considerable differences in pain, in factors influencing the pain, and in pain behavior across BMS patients. This indicates that patient information and education as well as treatment of BMS pain should be individualized.

Subjective sensory symptoms associated with axonal and demyelinating nerve injuries after mandibular sagittal split osteotomy.

PURPOSE: The effect of the type of nerve injury on subjective sensory disturbances and recovery has not been addressed in orthognathic surgery. Using neurophysiologic monitoring during 19 bilateral sagittal split osteotomy operations, we were able to classify intraoperative inferior alveolar nerve injuries as either axonal or demyelinating. This study aimed to analyze the quality and extent of the subjective sensations experienced by the patients after these 2 injury types at different time points up to 12 months. MATERIALS AND METHODS: Of the 36 injured nerves, 21 showed signs of demyelinating injury and 15 showed signs of axonal damage. The quality of subjective sensory symptoms was asked about at 2 weeks and 1, 3, 6, and 12 months postoperatively and classified into 4 categories: normal, negative, positive (including pain), and mixed sensations. In addition, the extent of the sensory alteration was determined by measuring the affected skin regions from symptom charts. RESULTS: The quantity, quality, and evolution of experienced subjective sensations differed between the injury types during follow-up: Subjective sensations normalized more rapidly after demyelinating-type injuries than after axonal-type injuries. Persistence of mixed sensation patterns at 3 months and appearance instead of disappearance of positive sensory phenomena after 3 months indicated axonal damage. Painful sensations at 1 month or later after surgery indicated axonal damage and predicted poor recovery and more long-term sequelae. CONCLUSIONS: Postoperative pain at 1 month and type of nerve injury are important prognostic factors for the persistence of subjective symptoms and development of neuropathic pain.

Neurophysiology and genetics of burning mouth syndrome.

BACKGROUND AND AIMS: Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS. METHODS: Forty-five BMS patients (43 women), mean age 62.5 years, and 32 healthy controls (30 women), mean age 64.8 years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed. RESULTS: Cool (p = 0.0090) and warm detection thresholds (p = 0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p = 0.0056). The latencies of R2 component were longer in BMS patients than in controls (p = 0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p = 0.0312) in homozygous patients with 957TT, who also reported most interference (p = 0.0352) and greatest suffering (p = 0.0341). Genotype 957CC associated with sleep disturbances (p = 0.0254). CONCLUSIONS: Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain. SIGNIFICANCE: The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

Explanatory Models of Illness and Treatment Goals in Temporomandibular Disorder Pain Patients Reporting Different Levels of Pain-Related Disability.

AIMS: To explore whether temporomandibular disorder (TMD) pain patients reporting different levels of pain-related disability differ in terms of illness explanations and treatment expectations. METHODS: Consecutive TMD pain patients (n = 399; mean ± SD age, 40.5 ± 12.7 years; 83% women) seeking treatment in primary care completed the Explanatory Model Scale (EMS). Patients were asked to indicate their expectations regarding the treatment. Each patient's pain-related disability level was determined using the Graded Chronic Pain Scale, with scores indicating no (0 disability points), low (1-2 disability points), or high (3-6 disability points) disability. Differences between EMS factor scores were evaluated using the Mann-Whitney U test. Differences between study groups were analyzed using logistic regression. RESULTS: High-disability patients considered physical and stress factors as more important in causing and in aggravating pain and as targets of treatment compared with patients with no disability (P = .0196 and P = .0251, respectively). The great majority of patients indicated they would like to receive information, decrease pain, and increase jaw function, with no significant subtype differences noted. Compared with no-disability patients, low-disability and high-disability patients were more likely to expect increased ability to perform daily functions (P < .0001 in both comparisons), increased work ability (P < .0001 in both comparisons), and better stress management skills (P = .0014 and P = .0001, respectively). CONCLUSION: Illness explanations and goals for treatment differ in patients reporting different levels of TMD pain-related disability.

Subtyping patients with temporomandibular disorders in a primary health care setting on the basis of the research diagnostic criteria for temporomandibular disorders axis II pain-related disability: a step toward tailored treatment planning?

AIMS: To use the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II and additional pain-related and psychosocial variables to identify subtypes of TMD patients in a primary health care setting based on pain-related disability. METHODS: Consecutive TMD pain patients (n = 399) seeking treatment in a primary care setting completed a multidimensional pain questionnaire. Subtyping was based on the Graded Chronic Pain Scale (GCPS), and the patients were divided into a no-disability group (0 disability points), lowdisability group (1-2 disability points), and high-disability group (3-6 disability points). Psychosocial variables included RDC/TMD Axis II variables, anxiety, tension and stress, worry, catastrophizing, coping ability, general health, and other pain problems. Subtype differences were analyzed with t test, Wilcoxon rank-sum test, ANOVA, or Kruskal-Wallis test. A further analysis with multivariable logistic model was applied. All P values from pairwise comparisons were Bonferroni adjusted. RESULTS: Most (61%) of the patients belonged to the no-disability group, 27% to the low-disability group, and 12% to the high-disability group. When subtypes were compared, patients in the no-disability group appeared psychosocially well-functioning, with fewer symptoms related to psychosocial distress, better ability to control pain, and fewer jaw functional limitations and other pain problems. Patients in the high-disability group reported the highest levels of symptoms of depression and somatization, sleep dysfunction, worry, and catastrophizing thoughts. The low-disability patients formed an intermediate group between the no-disability and high-disability groups. CONCLUSION: The results suggest that GCPS-related disability scoring can be used as a simple screening instrument in primary care settings to identify individuals with different, clinically relevant psychosocial subtypes.

Sensory dysfunction in burning mouth syndrome.

Our preliminary observations on a small group of burning mouth syndrome (BMS) patients indicated a change in the non-nociceptive, tactile sensory function in BMS and provided evidence for the hypothesis of a neuropathic etiology of BMS. In the present clinical study on a group of 52 BMS patients, we used quantitative sensory tests (QST) in addition to the blink reflex (BR) recordings in order to gain further insight into the neural mechanisms of BMS pain. Based on electrophysiologic findings, the BMS patients could be grouped into four different categories: (1) The results of the BR were suggestive of brainstem pathology or peripheral trigeminal neuropathy in ten (19%) patients. In most of the cases, the abnormalities in the BR seemed to represent subclinical changes of the trigeminal system. (2) Increased excitability of the BR was found in the form of deficient habituation of the R2 component of the BR in 11 (21%) of the patients. Two of these patients also showed signs of warm allodynia in QST. (3) One or more of the sensory thresholds were abnormal indicating thin fiber dysfunction in altogether 35 patients (76%) out of the 46 tested with QST. Thirty-three of these patients showed signs of hypoesthesia. (4) There were only five patients with normal findings in both tests. The present findings with strong evidence for neuropathic background in BMS will hopefully provide insights for new therapeutic strategies.

Abnormalities of the blink reflex in burning mouth syndrome.

To our knowledge, this is the first report on pain-related abnormalities of the eye blink reflex (BR) in a clinical pain patient population. The objective of this study was to evaluate the possible neuropathic mechanisms underlying the burning mouth syndrome (BMS), by means of objective electrophysiological examination of the trigemino-facial system. We studied the BR with stimulation of the supraorbital nerve (SON) with particular emphasis on the occurrence of the pain-related ultralate R3 components, and the habituation response of the R2 components. The subjects consisted of eleven BMS patients and 10 healthy control subjects. All patients underwent thorough clinical oral and neurological examinations. The motor function of the trigeminal nerve was assessed with a jaw reflex recording, and a needle-EMG examination of the facial and masticatory muscles was performed in the patients with abnormalities in the BR recordings. The jaw reflexes, the latencies of the BR components, and the needle-EMG examinations were normal in all patients. As a group, the BMS patients had statistically significantly higher stimulus thresholds for the tactile R 1 components of the BR compared with the control subjects. With non-noxious stimulation, the BMS patients showed more frequently pain-related R3 components (11/22 SONs) compared with the controls (3/20 SONs). In addition, four BMS patients had abnormal habituation of the R2 components. In two of these patients, the findings were segmental (i.e., unilateral), coinciding with the side of the subjective BM symptoms. The abnormalities of the BR tests appeared to be related to longer disease duration. Our results suggest a possible pathologic involvement of the nervous system in chronic BMS.

Role of the dopaminergic system in chronic pain -- a fluorodopa-PET study.

Recent data from animal experiments suggest an important role for the basal ganglia in the processing and sensorimotor gating of nociceptive information. However, very little is known about their possible participation in human pain. Because of our previous finding of increased excitability of the blink reflex (a brainstem reflex under dopaminergic inhibitory control) in some burning mouth syndrome (BMS) patients, we have studied the dopaminergic function of the striatum (putamen and caudatus) of BMS patients with positron emission tomography (PET). 6-[(18)F]fluorodopa (FDOPA) PET scans were done on ten BMS patients and 14 healthy control subjects. The presynaptic dopaminergic function was significantly decreased in the right putamen (20%, P=0.04) of the BMS patients compared to control subjects. On the left side, the FDOPA uptake was decreased by 17% (P=0.08). The mean FDOPA uptake was not significantly changed in the caudate nucleus of the patients. The finding of decreased striatal FDOPA uptake in the putamen supports our previous neurophysiological observations indicating decreased dopaminergic inhibition in BMS patients. The present result provides direct evidence of the involvement of the nigrostriatal dopaminergic system in pain for the first time in a clinical pain condition.

Occlusal treatments in temporomandibular disorders: a qualitative systematic review of randomized controlled trials.

Occlusal treatments (occlusal splints and occlusal adjustment) are controversial but widely used treatment methods for temporomandibular disorders (TMD). To investigate whether studies are in agreement with current clinical practices, a systematic review of randomized controlled trials (RCTs) of occlusal treatment studies from the period 1966 to March 1999 was undertaken. Eighteen studies met the inclusion criteria, 14 on splint therapy, and 4 on occlusal adjustment. The trials were scored using the quality scale presented by Antczak et al., 1986a (A.A. Antczak, J. Tang, T.C. Chalmers, Quality assessment of randomized control trials in dental research. I. Methods, J. Periodontal Res. 1986a;21:305-314). The overall quality of the trials was fairly low, the mean quality score was 0.43/1.00 (range 0.12-0.78). The most obvious methodological shortcomings were inadequate blinding, small sample sizes, short follow-up times, great diversity of outcome measures and numerous control treatments, some of unknown effectiveness. Splint therapy was found superior to 3, and comparable to 12 control treatments, and superior or comparable to 4 passive controls, respectively. Occlusal adjustment was found comparable to 2 and inferior to one control treatment and comparable to passive control in one study. Because of the methodological problems, only suggestive conclusions can be drawn. The use of occlusal splints may be of some benefit in the treatment of TMD. Evidence for the use of occlusal adjustment is lacking. There is an obvious need for well designed controlled studies to analyse the current clinical practices.

Altered dopamine D2 receptor binding in atypical facial pain.

Animal studies suggest that the dopaminergic system plays a role in central pain modulation. We have previously demonstrated with positron emission tomography (PET) that striatal dopaminergic hypofunction may be involved in the burning mouth syndrome. The aim of the present study was to evaluate the nigrostriatal dopaminergic system in patients with atypical facial pain using PET. In seven patients with atypical facial pain, striatal presynaptic dopaminergic function was assessed with [18F]FDOPA and dopamine D1 and D2 receptor availabilities with [11C]NNC 756 and [11C]raclopride, respectively. The results were compared with those of healthy controls. A quantitative region-of-interest analysis showed that the uptakes of [18F]FDOPA and [11C]NNC 756 did not differ between patients and controls. There was a tendency of increased D2 receptor availability in the left putamen (P=0.056), and the D1/D2 ratio in the putamen was decreased bilaterally by 7.7% (P=0.002) in patients when compared to controls. In a voxel-based analysis, the uptake of [11C]raclopride was increased in the left putamen (P=0.025). In conclusion, the increase in D2 receptor availability in the left putamen and the decrease in D1/D2 ratio imply that alterations in the striatal dopaminergic system as evaluated by PET may be involved in chronic orofacial pain conditions.

Striatal dopamine D1 and D2 receptors in burning mouth syndrome.

Animal studies have indicated that the nigrostriatal dopaminergic system is involved in central pain modulation. In a recent positron emission tomography (PET) study, we demonstrated presynaptic dysfunction of the nigrostriatal dopaminergic pathway in burning mouth syndrome, which is a chronic pain state. The objective of the present study was to examine striatal dopamine D1 and D2 receptors in these patients. We used 11C-NNC 756 and 11C-raclopride to study D1 and D2 receptor binding in a PET study in ten burning mouth patients and 11 healthy controls. Patients underwent a structured psychiatric evaluation and an electrophysiological test for the excitability of the blink reflex. The striatal uptake of 11C-NNC 756 did not differ between patients and controls. In a voxel-level analysis, the uptake of 11C-raclopride was statistically significantly higher in the left putamen in burning mouth patients (corrected P-value 0.038 at cluster-level). In the region of interest analysis, the D1/D2 ratio was 7.7% lower in the right putamen (0.64+/-0.04 vs. 0.69+/-0.04, P=0.01) and 6.4 % lower in the left putamen (0.65+/-0.05 vs. 0.70+/-0.05, P=0.05) when compared to controls. Increased 11C-raclopride uptake and the subsequent decrease in the D1/D2 ratio may indicate a decline in endogenous dopamine levels in the putamen in burning mouth patients.