Journal of Oral & Facial Pain and Headache, 02/2010

Aims: To evaluate the quality of methods used in randomized controlled trials (RCTs) of treatments for management of pain and dysfunction associated with temporomandibular muscle and joint disorders (TMJD) and to discuss the implications for future RCTs. Methods: A systematic review was made of RCTs that were implemented from 1966 through March 2006, to evaluate six types of treatments for TMJD: orthopedic appliances, occlusal therapy, physical medicine modalities, pharmacologic therapy, cognitive-behavioral and psychological therapy, and temporomandibular joint surgery. A quality assessment of 210 published RCTs assessing the internal and external validity of these RCTs was conducted using the Consolidated Standards of Reporting Trials (CONSORT) criteria adapted to the methods of the studies. Results: Independent assessments by raters demonstrated consistency with a mean intraclass correlation coefficient of 0.63 (95% confidence interval). The mean percent of criteria met was 58%, with only 10% of the RCTs meeting the four most important criteria. Conclusions: Much of the evidence base for TMJD treatments may be susceptible to systematic bias and most past studies should be interpreted with caution. However, a scatter plot of RCT quality versus year of publication shows improvement in RCT quality over time, suggesting that future studies may continue to improve methods that minimize bias. Keywords: quality, randomized clinical trials, temporomandibular, tension type headache, TMD, TMJ

Aims: To assess the effectiveness of acupuncture for the symptomatic treatment of temporomandibular disorders (TMD) from a review of studies using randomized controlled trials (RCTs). Methods: Electronic databases were systematically searched for articles reporting RCTs investigating acupuncture for TMD. The methodological qualities of eligible studies were assessed using the criteria described in the Cochrane Handbook. Results: Nineteen reports were systematically reviewed. There was moderate evidence that classical acupuncture had a positive influence beyond those of placebo (three trials, 65 participants); had positive effects similar to those of occlusal splint therapy (three trials, 160 participants); and was more effective for TMD symptoms than physical therapy (four trials, 397 participants), indomethacin plus vitamin B1 (two trials, 85 participants), and a wait-list control (three trials, 138 participants). Only two RCTs addressed adverse events and reported no serious adverse events. Conclusion: This systematic review noted moderate evidence that acupuncture is an effective intervention to reduce symptoms associated with TMD. There is a need for acupuncture trials with adequate sample sizes that address the long-term efficacy or effectiveness of acupuncture. Keywords: acupuncture, myofascial pain, randomized controlled trials, systematic review, temporomandibular disorders

Aims: To review evidence for chronic orofacial pain management using cognitive behavioral therapy (CBT). Methods: Electronic databases were searched for randomized controlled trials in which CBT was compared either alone or in combination with other forms of therapy for management of chronic orofacial pain. The quality of trials was assessed blind by three authors using a validated scale that had been specifically designed to score the quality of randomized controlled trials for psychological interventions. Author agreement was assessed using interclass correlation co-efficients. Results: Fourteen potentially relevant randomized controlled trials were identified. Seven trials were excluded, leaving seven for analysis; two studies were merged as they included the same trial and therefore six trials were used in the final analysis. All but one of the randomized controlled trials identified were based on temporomandibular disorders (TMD). Scoring of the trials showed that the three raters were in close agreement, with four trials performing well (scores of 22-35) whilst the remaining two trials were poor (scores 18). Of the four trials, one did not show any improvement with CBT prior to conservative treatment whilst the other three showed that CBT alone or in conjunction with conservative treatment improved both short-term and long-term outcomes in functional, dysfunctional, and chronic TMD patients. Conclusions: CBT, either alone or in combination with biofeedback, conservative treatment and/or self-care, can improve outcomes for patients with TMD in secondary care. However, further research is needed to assess its effectiveness in primary care and in management of other chronic orofacial pain conditions. Further, the number of sessions needed, mode of delivery, and cost-effectiveness also remain unclear. Keywords: chronic orofacial pain, cognitive behavioral therapy, randomized controlled trials, review

Aim: To determine if glutamate injected into the healthy temporomandibular joint (TMJ) evokes pain through peripheral N-methyl-D-aspartate (NMDA) receptors and if such pain is influenced by sex or sex steroid hormones. Methods: Sixteen healthy men and 36 healthy women were included and subjected to two randomized and double-blind intra-articular injections of the TMJ. Experimental TMJ pain was induced by injection of glutamate (1.0 mol/L) and NMDA block was achieved by co-injection of the NMDA antagonist ketamine (10 mmol/L). The TMJ pain intensity in the joint before and during a 25-minute postinjection period was continuously recorded on an electronic visual analog scale (0 to 10). Estradiol, progesterone, and testosterone levels in serum were analyzed. Results: Glutamate-induced pain showed a median (25/75 percentile) duration of 8.3 (5.2/12.2) minutes. The peak pain intensity was 6.1 (4.2/8.2), the time to peak was 50 (30/95) seconds, and the area under the curve was 59 (29/115) arbitrary units. The women reported higher maximum pain intensity than the men and shorter time to peak. The sex hormone levels were not significantly related to the glutamate-induced TMJ pain. NMDA block significantly reduced the glutamate-induced TMJ pain, mainly in the women. There were no significant correlations between sex hormone levels and the effects of NMDA block for any pain variable. Conclusion: Glutamate evokes immediate pain in the healthy human TMJ that is partly mediated by peripheral NMDA receptors in the TMJ. Keywords: glutamate, NMDA, pain, sex hormones, temporomandibular joint

Aims: To investigate key factors associated with treatment-seeking for orofacial pain symptoms in community-dwelling adult Chinese people in Hong Kong. Methods: A cross-sectional study was conducted using a Hong Kong Hospital Authority Family Medicine Clinic as the sampling frame. People aged 35 to 70 years with recent orofacial pain symptoms participated. Standard questions were asked about orofacial pain symptoms and characteristics in the previous month, Oral Health Impact Profile (OHIP-14), General Health Questionnaire (GHQ-12), Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) depression/nonspecific physical symptoms (NPS) scales, sleep and illness behavior measures, and questions on pain disability, professional treatment-seeking, pain medication usage, and dental attendance were administered prior to a standard clinical assessment. Multiple logistic regression with a forward stepwise selection method was used for data analysis. Results: Two hundred people with orofacial pain symptoms participated in the definitive study. Twenty-seven percent had sought professional advice. The majority had consulted a medical practitioner (66.7%) or dentist (40.7%), 16.7% had consulted a traditional Chinese medicine (TCM) practitioner, and the majority (60%) had taken pain medication. There was no significant association between different orofacial pain diagnoses and professional treatment-seeking (P = .602). Four independent factors were significantly related to an increased likelihood of treatment-seeking (P .05): more frequent dental attendance for check-up (odds ratio [OR] > 3), time when pain was experienced during the past month (days) (OR > 5), multiple pain symptoms (OR = 4.99), and use of TCM when ill (OR = 3.31). Conclusion: Professional treatment-seeking for orofacial pain was low in this ethnic group. The strongest predictor of treatment-seeking for orofacial pain was an increase in the number of days when pain was experienced during the past month. Key factors associated with treatment-seeking should be considered when formulating community health outreach programs. A further validation study with a larger sample size is recommended to confirm the present findings. Keywords: associated factors, Chinese, orofacial pain, treatment- seeking

Aims: To evaluate the predictive potential of preoperative psychological and psychophysiological variables in estimating severity of postoperative pain following mandibular third molar surgery (MTMS). Methods: Following ethical committee approval and informed consent, 40 consecutive patients scheduled for MTMS were included. Preoperative psychometric indicators of anxiety, depression, and vulnerability were evaluated by patient questionnaires. Thermal thresholds and heat pain perception (1 second phasic stimuli: 44°C to 48°C) were evaluated with quantitative sensory testing techniques. Standardized surgery was performed during local anesthesia. Postoperative pain management was with rescue paracetamol and ibuprofen. The patients were instructed to record each day their pain at rest and during dynamic conditions, and their requirement of analgesics for 14 days following surgery. Results: Thirty-eight patients completed the study. Eight patients were readmitted because of pain. During the postoperative period, one or more episodes of moderate to severe pain (> 30 on a visual analog scale) was reported by 60% (23/38) at rest, 63% (24/38) during mouth-opening, and 73% (28/38) during eating. In a multiple regression model, the combination of psychological vulnerability and heat pain perception rendered a predictive model that could account for 15 to 30% of the variance in postoperative pain during resting and dynamic conditions (P = .03 to .001). Conclusion: Implementation of clinically relevant preoperative screening methods may offer more efficacious postoperative pain therapies to pain-susceptible individuals undergoing mandibular third molar surgery. Keywords: mandibular third molar surgery, pain measurement/ methods, pain postoperative, predictive value of tests, quantitative sensory testing

Aims: To evaluate the presence of temporomandibular disorders (TMD) in systemic sclerosis (SSc) patients and its possible association with the severity of skin involvement. Methods: The presence of TMD was evaluated in 35 SSc women and 30 age- and sex-matched healthy controls by means of the anamnestic (Ai) and clinical (Di) Helkimo indices; the jaw mobility was further analyzed (MI). Skin involvement was scored by the Modified Rodnan Skin Score (MRSS). Results: Signs and symptoms of TMD were more frequent in SSc patients than in controls, the frequency distribution of the different clinical dysfunction indices differing significantly (P .001) between patients (Di0 8.6%, DiI 48.6%, DiII 22.8%, and DiIII 20%) and controls (Di0 50%, DiI 33.3%, and DiII 16.7%). Cyclophosphamide for severe and rapidly progressive cutaneous fibrosis was prescribed in six out of seven patients with severe signs (DiIII), in contrast this treatment was indicated for only two out of 25 patients with mild to moderate signs (DiI and DiII, P .001). Impaired jaw mobility was more frequent in SSc patients than controls (P .001). It was severe in 77.1% (MIII) and mild in 22.9% (MII) of the cases, in contrast to controls (MI0 33.4%, MII 53.3%, and MIII 13.3%; P .001). Approximately half of SSc patients with severe (MIII) but none of those with mild impairment were on cyclophosphamide treatment for severe cutaneous fibrosis (P = .02). Conclusion: Severe signs of TMD according to the anamnestic and clinical Helkimo indices were very frequent in SSc patients. Keywords: Helkimo indices and fibrosis, systemic sclerosis, temporomandibular disorders, temporomandibular joint

Aims: To examine the antinociceptive effects of N-Methyl-D-aspartate (NMDA) receptor NR2 subunit antagonists in a rat model of the facial formalin test. Methods: Experiments were carried out on adult male Sprague-Dawley rats weighing 220 to 280 g. Anesthetized rats were individually mounted on a stereotaxic frame and a polyethylene tube was implanted for intracisternal injection and, 72 hours later, formalin tests were performed. NMDA receptor antagonists were administered intracisternally 10 minutes prior to subcutaneous injection of 5% formalin (50 µL) into the vibrissal pad. Results: The intracisternal administration of 25, 50, or 100 µg of memantine, an antagonist that acts at the NMDA ion channel site, significantly suppressed the number of scratches in the second phase of the behavioral responses to formalin. Intracisternal administration of a range of doses of 5,7-dichlorokynurenic acid, a glycine site antagonist, or DL-2-amino-5-phosphonopentanoate (AP-5), a nonselective NMDA site antagonist, produced significant antinociceptive effects in the second phase. Intracisternal administration of 1, 2.5, or 5 µg of (2R,4S)-4-(3 Phosphonopropyl)-2-piperidine-carboxylic acid (PPPA), a competitive NR2A antagonist, significantly suppressed the number of scratches in the second phase, while only the highest dose of PPPA (5 µg) significantly suppressed the number of scratches in the first phase. The antinociceptive effects of intracisternal injection of (αR,ßS)-α-(4Hydroxyphenyl)-ß methyl-4-(phenylmethyl)-1-Piperidinepropanol maleate(Ro 25-6981), a selective NR2B antagonist, were similar to those of PPPA. Injection of memantine, AP-5, Ro 25-6981, or vehicle did not result in any motor dysfunction. A low dose of PPPA (1 µg) or 5,7-dichlorokynurenic acid (2.5 µg) did not affect motor function. However, higher doses of PPPA and 5,7-dichlorokynurenic acid produced motor dysfunction. Conclusion: The present results suggest that central NR2 subunits play an important role in orofacial nociceptive transmission. Moreover, this data also indicate that targeted inhibition of the NMDA receptor NR2 subunit is a potentially important new treatment approach for inflammatory pain originating in the orofacial area. Keywords: antinociception, formalin, NMDA, NR2 receptor, orofacial pain

This case report presents a patient with tardive dyskinesia who also suffered from masticatory muscle pain and temporomandibular joint osteoarthrosis. The patient was treated with clozapine in gradually increasing doses and two injections of botulinum toxin type A one year apart. Involuntary movements of mandibular clenching and bruxing disappeared and pain was relieved to a great extent. Reappearances of dyskinetic movements and pain were observed during the follow-up period of 1.5 years. Keywords: antipsychotic, botulinum toxin type A, clozapine, tardive dyskinesia, temporomandibular disorder