Treatment of painful temporomandibular joints with a cyclooxygenase-2 inhibitor: a randomized placebo-controlled comparison of celecoxib to naproxen. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: a pilot study. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. The effectiveness of adding pharmacologic treatment with clonazepam or cyclobenzaprine to patient education and self-care for the treatment of jaw pain upon awakening: a randomized clinical trial. Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial. [Piroxicam, diazepam and placebo in the treatment of temporomandibular joint dysfunction. Double blind study]. Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area. Use of Theraflex-TMJ topical cream for the treatment of temporomandibular joint and muscle pain. Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study. Diclofenac sodium as an alternative treatment of temporomandibular joint pain.
To compare the efficacy and adverse effects of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with naproxen, a non-steroidal anti-inflammatory drug, and placebo in the treatment of painful temporomandibular joints (TMJs). In this randomized, double-blind, placebo-controlled trial, 68 subjects with painful TMJs secondary to disc-displacement with reduction, received celecoxib 100 mg twice a day; naproxen, 500 mg twice a day; or placebo for 6 weeks. Subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analogue scale, maximal comfortable mandibular opening, and quality of life (SF-36), at baseline (1 week after discontinuing previous analgesic therapy) and again after 6 weeks of drug treatment. Naproxen significantly reduced the symptoms of painful temporomandibular joint disc-displacement (TMJ DD) with reduction as determined by most efficacy measures. Significant improvement in pain intensity occurred within 3 weeks of treatment, and was sustained throughout the 6-week study. Clinically significant improvement in mandibular range of motion was observed for naproxen compared to celecoxib and placebo. Celecoxib showed slightly better pain reduction than placebo, but was not significantly effective for temporomandibular disorder pain. Celecoxib and naproxen were well tolerated, with similar number of reported adverse effects. Dual COX-1 and COX-2 inhibition with naproxen was demonstrated to be effective for the treatment of painful TMJs, as seen by significant improvement in clinical signs and symptoms of TMJ DD with reduction compared to celecoxib and placebo. Inhibition of both COX isozymes is needed to achieve effective analgesia for this type of musculoskeletal pain. Previous studies have shown chondroitin sulfate and glucosamine hydrochloride have beneficial effects on symptoms of osteoarthritis of the knee. Our aim was to study the effect of a daily dose of 1500 mg of glucosamine hydrochloride (GH) and 1200 mg of chondroitin sulfate (CS) taken for twelve weeks on subjects diagnosed with capsulitis, disk displacement, disk dislocation, or painful osteoarthritis of the temporomandibular joint (TMJ). Forty-five subjects were enrolled in the study and were randomly assigned to either an active medication group or a placebo group. Eleven subjects were lost from the study for various reasons, resulting in fourteen subjects remaining in the active medication group and twenty subjects remaining in the placebo group. Subjects taking CS-GH had improvements in their pain as measured by one index of the McGill Pain Questionnaire, in TMJ tenderness, in TMJ sounds, and in the number of daily over-the-counter medications needed. Subjects taking the placebo medication had improvements in their pains as measured by the visual analog scale and by four indices of the McGill Pain Questionnaire. Additional studies are required to evaluate the clinical effectiveness of CS-GH and to determine the exact mechanism by which CS-GH affects the articular cartilage of synovial joints. Three common haplotypes in the gene encoding catechol-O-methyltransferase (COMT) have been associated with pain modulation and the risk of developing chronic musculoskeletal pain, namely temporomandibular disorder (TMD). Haplotypes coding for higher enzymatic activity were correlated with lower pain perception. Rodent studies showed that COMT inhibition increases pain sensitivity through beta2/3-adrenergic receptors. We hypothesized that the nonselective beta-adrenergic antagonist propranolol will reduce clinical and experimental pain in TMD patients in a manner dependent on the individuals' COMT diplotype.
                Forty Caucasian female participants meeting the Research Diagnostic Criteria for TMD were genotyped for COMT polymorphisms and completed a randomized, double-blind, placebo-controlled, two-period crossover pilot study. Each period consisted of a baseline assessment week followed by an intervention week (propranolol or placebo). Changes in clinical pain ratings, psychological status, and responses to heat and pressure stimuli between baseline and intervention weeks were compared across periods.
                The number of patients reporting a reduction in pain intensity rating was greater during propranolol treatment (P=0.014) compared with placebo. Propranolol significantly reduced a composite pain index (P=0.02) but did not decrease other clinical and experimental pain ratings. When stratified by the COMT high activity haplotype, a beneficial effect of propranolol on pain perception was noted in patients not carrying this haplotype, a diminished benefit was observed in the heterozygotes, and no benefit was noted in the homozygotes.
                COMT haplotypes may serve as genetic predictors of propranolol treatment outcome, identifying a subgroup of TMD patients who will benefit from propranolol therapy. To compare the relative effectiveness of a benzodiazepine (clonazepam), a muscle relaxant (cyclobenzaprine), and a placebo for the treatment of jaw pain upon awakening, when each is combined with the recommended nonpharmacological components of initial medical management.
                Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All subjects were given education about TMD and a self-care program. Subjects were randomized into 1 of 3 groups: clonazepam (0.5 mg/night), cyclobenzaprine (10 mg/night), or placebo. The primary outcome measure was the subjects' average intensity of jaw pain upon awakening over the prior week. This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial. A secondary outcome measure was sleep quality based on the Pittsburg Sleep Quality Index.
                Within-group changes showed a statistically significant (P < .001) decrease in jaw pain upon awakening for all 3 groups. Between-group differences demonstrated a statistically significant difference (P < .016) between cyclobenzaprine and placebo, and between cyclobenzaprine and clonazepam. There was no significant effect on sleep quality in any group.
                This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening. Based on the subjects' report of sleep quality, these medications failed to significantly improve sleep in the short term. Chronic masticatory myalgia (CMM) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system. The antiepileptic agent gabapentin acts centrally and is used for managing different types of chronic pain conditions. The objective of this study was to evaluate the analgesic action of gabapentin on CMM. In this 12-week randomized controlled clinical trial 50 patients were randomly allocated into two study groups: 25 received gabapentin and 25 received placebo. The outcome measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI) and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty-six patients completed the study. Gabapentin showed to be clinically and statistically superior to placebo in reducing pain reported by patients (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded from this study that gabapentin is effective for the management of CMM. The effects of Piroxicam, Diazepam, and a Placebo on patients of different degrees of Stomatognathic System Dysfunction were studied. No statistically significant differences were found between the therapeutic effects of Piroxicam, Diazepam and a placebo. To determine the effectiveness of topical capsaicin cream application on localized pain in the temporomandibular joint (TMJ) area.
                A randomized, double-blind, placebo-controlled study was conducted on 30 patients suffering from unilateral pain in the TMJ area. Patients were randomly divided into experimental and placebo groups; they were instructed to apply 0.025% capsaicin cream or its vehicle to the painful TMJ area 4 times daily for 4 weeks. Subjective parameters of present pain, most severe pain, effect of pain on daily activities, and pain relief were assessed each week on a visual analog scale. Muscle and joint sensitivity to palpation on the painful and contralateral joints and maximal mouth opening (assisted/passive and non-assisted/active) were examined weekly by the same experienced examiner.
                Capsaicin cream produced no statistically significant influence on measured variables when compared to placebo. Both experimental and placebo groups showed statistically significant improvement in most variables during the experiment.
                The factor of time had a major effect in the non-specific improvement of the parameters assessed. The placebo effect played an important role in the treatment of patients with pain in the TMJ area. This randomized, double-blind study was designed to evaluate the effectiveness of the topical cream Theraflex-TMJ (NaBob/Rx, San Mateo, CA) in patients with masseter muscle pain and temporomandibular joint (TMJ) pain. Fifty-two subjects (5 males and 47 females) were instructed to apply a cream over the afflicted masseter muscle(s) or over the jaw joint(s) twice daily for two weeks. Theraflex-TMJ cream was used by the experimental group, while a placebo cream was used by the control group. The means of pain ratings were calculated prior to the application of the cream (baseline), after ten days of tx (period 1), and 15 days of tx (period 2) days of treatment and five days after stopping the treatment (follow-up). There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 (p < 0.01), period 2 (p < 0.001), and follow-up (p < 0.01). For the control group, no significant differences were found between the different time periods (p > 0.05). There was evidence of minor side effects such as skin irritation and/or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups. The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporomandibular joint. A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporomandibular disorder/myofascial pain patients who were not responsive to occlusal splint, behavioral, and physical therapy. Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic, anxiolytic, muscle relaxant, and sedative properties. Clonazepam appears to be effective when compared to a placebo. However, caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction. Indiscriminate administration of clonazepam may be harmful to the patient. In a double-blind study, diclofenac sodium (Voltaren), 50 mg two or three times a day, was compared with placebo in 32 patients with pain localized to the temporomandibular joint (TMJ). The patients were allocated into two equally large groups. A visual analog scale was used to estimate the pretreatment degree of pain. The treatment effect was assessed as the frequency of joint and muscle pain and by the patients' own evaluation of improvement. The change in the clinical condition was assessed by tenderness to palpation of the TMJ and masticatory muscles and by mandibular mobility. The frequency of TMJ pain showed a greater reduction in the diclofenac group than in the placebo group, and there was a significant reduction of daily TMJ pain in the diclofenac group. The diclofenac group also showed a significant decrease in tenderness to palpation of the masticatory muscles in comparison with the placebo group. The patients with short duration of pain showed the best response to diclofenac. There was no evidence in this study to prove that diclofenac should be used as a primary treatment of TMJ pain, but it could be used as a complement to other treatments of acute TMJ pain.
There is insufficient evidence to support or not support the effectiveness of the reported drugs for the management of pain due to TMD. There is a need for high quality RCTs to derive evidence of the effectiveness of pharmacological interventions to treat pain associated with TMD.