Journal of Oral & Facial Pain and Headache, 03/2017

Aims: To propose a visual method to screen and assess psychosocial functioning in temporomandibular disorder (TMD) pain patients in comparison with age- and gender-matched healthy controls by forming individual profiles and to evaluate the association between psychosocial profiles and quantitative sensory testing (QST) findings of TMD pain patients. Methods: TMD patients (n = 58) and control participants (n = 41) completed a set of questionnaires profiling their psychosocial function, and QST was performed at the temporomandibular joint (TMJ) on both sides of the face in all participants. Psychosocial parameters from the Research Diagnostic Criteria for TMD (RDC/TMD), Oral Health Impact Profile (OHIP), and Pain Catastrophizing Scale (PCS) instruments were transformed into T scores, and QST parameters were transformed into z scores based on reference data. Group differences for psychosocial T scores were analyzed with t tests. T scores of psychosocial parameters and z scores of QST parameters were correlated using Spearman's correlation (ρ). Results: Most (96.6%) TMD pain patients exhibited one or more parameters indicative of psychosocial distress, with psychological disability scores being the scores most frequently encountered outside the reference 95% confidence intervals (CI). TMD patients were psychosocially more distressed with regard to all psychosocial parameters compared with controls (P .009). After Bonferroni corrections, a significant correlation was detected between the sleep dysfunction parameter and mechanical detection threshold (MDT) in TMD pain patients (ρ = 0.427, P .001). Conclusion: T score psychosocial profiles created an easy overview of psychosocial function in TMD pain patients. Increased sensitivity to tactile stimuli was associated with higher sleep dysfunction T scores. Keywords: psychosocial profiles, quantitative sensory testing, T scores, temporomandibular disorders

Aims: To evaluate the contribution of the psychosocial and behavioral aspects of pain to the perception of oral health in a sample of Brazilian dental patients. Methods: This cross-sectional study involved 436 patients who sought dental care in the School of Dentistry of São Paulo State University and who reported some type of orofacial pain. The study group's mean age (± standard deviation [SD]) was 39.9 ± 13.6 years, and the sample was 74.5% female. The Portuguese version of the Oral Health Impact Profile Short Form (OHIP-14) and the Multidimensional Pain Inventory (MPI) were used. The data were included in a structural equation model in which perception of oral health was considered the dependent variable. The evaluation of the contribution of psychosocial and behavioral aspects of pain to the perception of oral health was based on the statistical significance of causal paths (β) evaluated by z tests (α = 5%). Results: The fit of the models of OHIP-14 and MPI were adequate. Interference, self-control, negative mood, and punishing responses provided significant contributions to the perception of oral health. The structural model presented adequate fit to the data (explained variance = 28.0%). Conclusion: These findings provide evidence that psychosocial and behavioral aspects of pain such as interference of pain in activities, self-control, negative mood, and punishing responses contribute to the perception of oral health. Keywords: facial pain, oral health, pain, perception, psychosocial impact

Aims: To evaluate and identify baseline characteristics of the adolescent patients included in two previous randomized controlled trials (RCTs) that may predict a clinically significant outcome after treatment of temporomandibular disorders (TMD) with an occlusal appliance (OA) or relaxation training (RT) in a clinical sample of adolescents. Methods: This study combined two patient samples from the earlier RCTs for a total of 167 adolescents with frequent TMD pain (once a week or more often), diagnosed according to the Research Diagnostic Criteria for TMD. They were treated with OA, RT, or received information only (control). Outcome (response to treatment vs nonresponse) was assessed using four measures: the Patient Global Impression of Change (PGIC), pain intensity rated on a numeric rating scale (NRS), pain frequency levels, and pain severity levels prospectively recorded in a pain diary. Predictors of outcome were evaluated posttreatment for the whole sample and at 6 months follow-up for participants from the first trial. Associations and differences between groups obtained in the bivariate analyses were further examined in subsequent multivariate logistic regression analyses. Results: At posttreatment, treatment condition (OA being more effective than RT/control), gender (boys being more responsive than girls), arthralgia (predicting lower response), lower levels of somatic complaints (predicting better response), and shorter TMD pain history (predicting better response) emerged as significant predictors of a clinical response. At 6-month follow-up, lower consumption of analgesics and shorter TMD pain history emerged as significant predictors of treatment outcome, while treatment condition approached significance after multivariate analysis. Conclusion: This study revealed that treatment condition and gender were the most consistent predictors of a clinically significant outcome across outcome measures in a clinical sample of adolescents with TMD. Treatment with OA reduced TMD pain in the adolescents. Keywords: adolescence, occlusal appliance, predictors, relaxation training, temporomandibular disorders

Aims: To carry out a systematic review of clinical trials published up to 2015 to determine the effectiveness of acupuncture in treating myofascial pain in temporomandibular disorder (TMD) patients. Methods: The databases used were the Cochrane Library, PubMed, Scopus, and Web of Science; the dates of the articles surveyed ranged from 1990 to May 2015. The inclusion criteria were: (1) publications in English, Portuguese, or Spanish; (2) controlled clinical trials; (3) patients with TMD of muscular origin; and (4) studies that used acupuncture or laser acupuncture only for treatment. Reference lists of the included articles were hand searched. Results: A total of four randomized clinical trials using acupuncture (traditional, trigger point, and laser) for TMD treatment met the eligibility criteria and were included. Although the studies featured small sample sizes and short-term follow-up periods, acupuncture yielded results similar to those observed in groups treated with occlusal splints and were significantly superior than those obtained from placebo acupuncture- treated groups. Conclusion: Despite the weak scientific evidence supporting its efficacy, acupuncture treatment appears to relieve the signs and symptoms of pain in myofascial TMD. More controlled and randomized clinical trials with larger sample sizes are needed in this field of research to verify these initial findings. Keywords: acupuncture therapy, controlled clinical trial, myofascial pain, temporomandibular joint dysfunction disorders

Aims: To assess the prevalence, 3-year course, and associated factors of temporomandibular joint (TMJ) pain in patients with newly diagnosed rheumatoid arthritis (RA). Methods: A total of 264 patients with newly diagnosed RA were included. Patients were assessed after 3 months, 6 months, 9 months, 1 year, 1.5 years, 2 years, and 3 years. TMJ pain was scored by manual palpation, and the prevalence of TMJ pain was calculated at baseline and at all seven follow-up intervals during 3 years. Factors assessed for a potential association with TMJ pain at baseline included: demographic factors (gender and age), disease-related factors (symptom duration, rheumatoid factor [RF], anti-cyclic citrullinated protein [anti-CCP], C-reactive protein [CRP], and Disease Activity Score 28 [DAS28]), and functional factors (Health Assessment Questionnaire [HAQ] and European Quality of Life 5 Dimensions Questionnaire [EQ5D]-anxiety/depression). A stepwise logistic regression model was used to determine factors associated with TMJ pain in patients with RA. Results: The prevalence of TMJ pain in patients with RA was 10.6% at baseline, which decreased to 3.6% in the first year after inclusion and remained stable thereafter. Disease activity as determined by the DAS28 was significantly associated with TMJ pain (odds ratio [OR] = 1.51; 95% confidence interval [95% CI] = 1.12-2.05; P = .009) at baseline. A second logistic regression analysis was performed with the following variables of the DAS28: erythrocyte sedimentation rate (ESR), tender joint count, swollen joint count, and global health. Tender joint count (OR = 1.06; 95% CI = 1.01-1.12; P = .03) and global health (OR = 1.02; 95% CI = 1.00-1.03; P = .03) were significantly associated with TMJ pain at baseline. The remaining factors included in the analysis were not significantly associated with TMJ pain at baseline. Conclusion: The prevalence of TMJ pain in patients with newly diagnosed RA is approximately 10% and decreases during follow-up, especially in the first year. Disease activity is a risk factor for TMJ pain in patients with newly diagnosed RA. Keywords: associated factors, course, early rheumatoid arthritis, prevalence, temporomandibular joint pain, TMD

Aims: To investigate the association between glucose and insulin metabolism and migraine, as well as between diabetes mellitus (DM) and migraine, at a Chinese community level. Methods: A community-based, case-control study was performed in Heihe City, China. A survey was conducted door to door by eight trained investigators. Migraine was diagnosed using the International Classification of Headache Disorders (ICHD-III) beta criteria. A total of 2,023 participants completed a questionnaire, underwent a physical examination, and donated fasting blood. After excluding 191 with reported DM, 1,832 participants were included in the study. Of these, 86 participants with migraine and 95 without migraine participated in a 75-g oral glucose tolerance test. Glycosylated hemoglobin (HbA1c) was assessed at 0 minutes and serum glucose and insulin levels were measured at 0, 30, 60, and 120 minutes after glucose loading. Data with skewed distributions were compared using rank sum test, and the associations between DM and migraine were analyzed with logistic regression. Results: There were no significant differences in HbA1c, homeostatic model assessment-insulin resistance (HOMA-IR), β-cell function index of HOMA, or quantitative insulin sensitivity check index (QUICKI) between the participants with migraine and without migraine. When participants without migraine were classified into DM, prediabetes, and normal glucose subgroups and compared with the corresponding migraine subgroups, participants in the migraine subgroup with prediabetes presented higher levels of fasting insulin and HOMA-IR and a lower QUICKI than the nonmigraine subgroup with prediabetes. Moreover, DM was negatively associated with migraine in the 181 subjects who participated in the OGTT; however, no association was found when all 1,832 participants were considered. Conclusion: Insulin resistance seems to exist in individuals with both migraine and prediabetes, and there is a possible negative association between DM and migraine. Keywords: association, diabetes mellitus, insulin resistance, migraine

Aims: To evaluate the validity of the Korean Migraine-Specific Quality of Life Questionnaire version 2.1 (K-MSQ v 2.1) in patients with episodic migraine (EM) or chronic migraine (CM). Methods: Subjects were recruited from a headache clinic and completed several self-report instruments, including the K-MSQ v 2.1, the Migraine Disability Assessment Scale (MIDAS), the Headache Impact Test-6 (HIT-6), the Migraine-Specific Quality of Life (MSQoL), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Some of the subjects were assessed 4 weeks later and underwent the K-MSQ v 2.1 to examine test-retest reproducibility. Internal consistency and test-retest reproducibility were assessed to determine reliability. Construct validity was also assessed. Internal consistency (Cronbach's α) and test-retest reproducibility (intraclass correlation coefficients) were assessed to determine reliability. Pearson correlations were used to determine the validity. Results: For the 180 eligible patients, the value of Cronbach's α for the three dimensions of the K-MSQ v. 2.1 (Role Function-Restrictive, Role Function-Preventive, and Emotional Function) were 0.954, 0.909, and 0.898, respectively, indicating excellent internal consistency. The intraclass correlation coefficients between baseline and the 4-week retest showed reliable reproducibility. The scores of the three dimensions for the K-MSQ v. 2.1 were well correlated with scores for the MIDAS, the HIT-6, the MSQoL, the PHQ-9, and the GAD-7. Internal consistency and construct validity showed similar tendencies in patients with EM and those with CM. Conclusion: The K-MSQ v 2.1 is a reliable and valid screening tool for evaluating QoL in patients with EM and CM. Keywords: chronic migraine, migraine, MSQ, quality of life, validation

Aims: To evaluate and compare the effectiveness of two concentrations of topical clonazepam solution in improving symptoms of burning mouth syndrome (BMS). Methods: A retrospective chart review was conducted of patients diagnosed with BMS and managed with topical clonazepam solution between 2008 and 2015. A 0.5-mg/mL solution was prescribed until 2012, when this was changed to a 0.1 mg/mL solution. Patients were instructed to swish with 5 mL for 5 minutes and spit two to four times daily. The efficacies of the two concentrations were compared using patientreported outcome measures at the first follow-up, including the reported percentage of improvement in burning symptoms and the change in burning severity from baseline ranked on an 11-point numeric rating scale (NRS). Response to treatment was compared between the two concentrations using Wilcoxon rank sum test. Results: A total of 57 subjects were included, 32 in the 0.1-mg/mL cohort and 25 in the 0.5-mg/mL cohort, and evaluated at a median follow-up of 7 weeks. The median overall percentage improvement was 32.5% in the 0.1-mg/mL cohort and 75% in the 0.5-mg/mL cohort. The median reduction in NRS score was 0.5 points in the 0.1-mg/mL cohort and 6 points in the 0.5-mg/mL cohort. The use of either outcome measure revealed that the response to treatment with the 0.5-mg/mL solution was superior to that of the 0.1 mg/mL solution (P .01). Conclusion: These findings suggest that a 0.5-mg/mL topical clonazepam solution is effective in the management of BMS. Future randomized clinical trials are warranted. Keywords: BMS, compounded rinse, oral burning, oral dysesthesia, topical treatment

Aims: To investigate cellular changes in the spinal trigeminal nucleus (STN) and trigeminal ganglion (TG) associated with trigeminal nociception mediated by inflammation in the temporomandibular joint (TMJ). Methods: Male Sprague- Dawley rats (n = 86) were utilized to investigate cellular and behavioral responses to prolonged TMJ inflammation caused by bilateral injection of Complete Freund's Adjuvant (CFA) in the TMJ capsules. To investigate the cellular effects of protein kinase A (PKA) in the STN, rats were injected intrathecally with the selective PKA inhibitor KT5720 prior to injection of CFA into both TMJ capsules. Levels of calcitonin gene-related peptide (CGRP), active PKA, and ionized calciumbinding adapter molecule 1 (Iba1) in the STN and expression of phosphorylated extracellular regulated kinases (p-ERK) in the TG were determined with immunohistochemistry (n ≥ 3 experiments per test condition). Nocifensive head withdrawal responses to mechanical stimulation of the cutaneous tissue over the TMJ were monitored following CFA injection in the absence or presence of KT5720 (n = 7). Statistical analysis was performed using parametric analysis of variance (ANOVA) tests. Results: Intrathecal injection of KT5720 significantly inhibited the stimulatory effect of CFA on levels of CGRP, PKA, and Iba1 in the STN. In addition, administration of KT5720 decreased the average number of CFA-induced nocifensive withdrawal responses to mechanical stimulation and the CFA-mediated increase in p-ERK expression in the ganglion. Conclusion: These findings provide evidence that elevated PKA activity in the STN promotes cellular events temporally associated with trigeminal nociception caused by prolonged TMJ inflammation. Keywords: calcitonin gene-related peptide, nociception, protein kinase A, TMJ, trigeminal ganglion

Aims: To determine whether estrogen status alters κ-opioid inhibition of nociceptive processing by affecting temporomandibular joint (TMJ) input to neurons in the trigeminal subnucleus caudalis [Vc]/C1-2 region at the spinomedullary junction in female rats. Methods: TMJ-responsive neurons were recorded in laminae I-II of the Vc/C1-2 region at the spinomedullary junction of ovariectomized female rats treated for 2 days with low-dose estradiol (LE group; 2 mg/day) or high-dose estradiol (HE group; 20 mg/day). Under isoflurane anesthesia, TMJ neurons were activated by adenosine triphosphate (ATP; 1 mM, 20 μl), which was injected into the joint space before and after cumulative doses of a κ-opioid receptor (KOR) agonist (U50488) given systemically (0.03, 0.3, and 3 mg/kg, intravenously) or by local application to the dorsal surface of the Vc/C1-2 region (1 and 10 nmol/30 μl). Analysis of variance and Newman-Keuls test were performed to compare the data. Results: Systemic U50488 caused a doserelated inhibition of ATP-evoked neuronal activity in HE rats and reduced the size of the neuronal cutaneous receptive field (RF), while effects in LE rats were not significant. Systemic U50488 reduced the spontaneous activity of TMJ-responsive neurons to similar levels in LE and HE groups. Locally applied U50488 inhibited ATP-evoked neuronal activity in HE rats, but not in LE rats. Systemic and local administration of the KOR antagonist nor-binaltorphinine (nor-BNI) partially reversed the decrease in Rmag induced by U50488, but had no effect on neurons from LE rats. Conclusion: These results indicate that KOR-dependent effects on TMJ-responsive neurons in the superficial laminae of the Vc/C1-2 region in female rats are differentially modified by high and low estrogen status. The site of action for estrogen-induced modulation of TMJ neuronal activity by KOR likely includes second-order neurons in the Vc/C1-2 region. Keywords: estrogenic effects, opioid analgesia, orofacial pain, temporomandibular joint, trigeminal brainstem