Journal of Oral & Facial Pain and Headache, 02/2003

Aims: Bruxism associated with drugs can be destructive, resulting in severe consequences to health that include destruction of tooth structure, irreversible harm to the temporomandibular joint, severe myofascial pain, and muscle contraction headache. However, reports concerning a possible association between bruxism and various pharmacologic drugs are scarce and mostly anecdotal. The purpose of this article was to review the existing literature concerning the exacerbating or ameliorating effect of drugs on bruxism in humans. Methods: A search of the MEDLINE, EMBASE, and PsicINFO databases from 1982 to 2001 was conducted, and the term bruxism and one of the following terms were used: drugs, medicine(s), pharmaceutical, movement disorders, akathisia, dyskinesia, dystonia, central or autonomic nervous system, dopamine, serotonin, and GABA. Furthermore, a search using the term bruxism was carried out on the weekly journal Reactions, which deals with side effects of drugs. Several chemical terms were searched separately (eg, caffeine, nicotine). Relevant information was also derived from reference lists of the retrieved publications. Results: The search yielded complex information referring to the association between bruxism and dopaminerelated drugs, antidepressant drugs, sedative and anxiolytic drugs, and drugs of abuse. Conclusion: There is insufficient evidencebased data to draw definite conclusions concerning the effects of various drugs on bruxism. Although certain substances related to the dopaminergic, serotonergic, and adrenergic systems suppress or exacerbate bruxist activity in humans and animals, the literature is still controversial, and based mostly on anecdotal case reports. More controlled, evidence-based research on this underexplored subject is needed. Keywords: bruxism, medication(s), drug(s), dopamine, serotonin, GABA, SSRI

Aims: To investigate whether the duration of chronic pain in temporomandibular disorder (TMD) patients is associated with a net depletion of amino acids, and a distinct process from pain intensity. Methods: Twenty-nine patients defined by the research diagnostic criteria/TMD as having Type 1a muscle pain (TMD1A group), and 34 age- and sex-matched control subjects, were assessed for variation in urinary organic and amino acid excretion by gas chromatography-mass spectrometry. Results: The TMD1A patients' mean pain intensity, assessed on a visual analog scale (VAS), was 5.4 (95% confidence limits: 4.5 to 6.3), TMD1A illness duration was 5.0 ± 1.2 (SD) years, number of body areas with pain/subject was 6.3 ± 2.4 (range 0 to 10), and symptom prevalence from the Symptom Check List-90-Revised (SCL-90-R) was 25.5 ± 11.3 symptoms/subject, which was higher than the controls (5.2 ± 5.0 symptoms/subject, P .001). TMD1A patient illness duration was positively correlated with symptom prevalence and body pain distribution, and all were independent of pain intensity. The TMD1A patients had: (1) an increased tyrosine:leucine ratio; and (2) reduced leucine concentrations (both P .001), which suggests deregulated catabolism. Pain intensity was associated with: (1) changes in the multivariate urinary metabolite excretion patterns (P .001); (2) reduced leucine concentrations (P .001); and (3) increases in total urinary metabolites (P .04), and in 2 unidentified molecules, UM28 (P .001) and CFSUM1 (P .002). TMD1A illness duration was associated with lower (1) urinary metabolite concentrations and (2) succinic acid and combined glutamine + glutamic acid levels, suggesting a progressive depletion of metabolite reserves. Conclusion: In TMD1A patients, total amino acid excretion was positively correlated with pain intensity and negatively correlated with illness duration, which indicated that illness duration was associated with a different set of metabolic anomalies compared with those identified for pain intensity. Keywords: pain, facial pain, fibromyalgia syndrome, temporomandibular joint dysfunction

Aims: To investigate the association between toxin-producing staphylococci, symptom expression, and changes in urinary excretion of metabolites in temporomandibular disorder (TMD) patients and age- and sex-matched control subjects. Methods: Twenty-nine patients defined by the research diagnostic criteria/TMD as having Type 1a muscle pain (TMD1A), and 34 age- and sex-matched control subjects were assessed for the carriage of staphylococcal species, staphylococcal toxin production, expression of symptoms, and changes in urinary excretion of amino and organic acids. Results: TMD1A patients had an increased incidence of carriage of toxin-producing coagulase-negative staphylococcus (MDT-CoNS, P .004), which produced increased levels of δ-like membrane-damaging toxins. The TMD1A patients also had a reduction in the incidence of carriage of Staphylococcus aureus (P .02). Increased incidence of MDTCoNS was positively associated with increased pain intensity as assessed by a visual analog scale (P .001). Odds ratio analysis revealed a 9.2-fold increase in MDT-CoNS recovery from the nose of TMD1A patients compared with the control subjects (odds ratio = 9.2, > 95% confidence limits: 2.3 to 37.5, P .001). Increases in the carriage incidence of MDT-CoNS were also associated with increases in the urinary tyrosine:leucine ratio (P .004), which represents a change in the balance of proteolysis and protein synthesis. The toxin production by these CoNS species was also associated with an increased urinary excretion of glutamic acid (P .03). Conclusion: These data suggest that an increased colonization of MDT-CoNS on skin and mucosal membranes was associated with changed proteolysis, increased pain intensity, and an increase in excitatory amino acids consistent with events associated with the development of chronic orofacial muscle pain in TMD patients. Keywords: facial pain, metabolism, microbiology, temporomandibular disorders, staphylococcus pathogenicity, staphylococcal haemolysins, staphylococcal toxicity

Aims: To compare the short-term efficacy of treatment with a stabilization appliance compared with that of a non-occlusal, control appliance in patients with temporomandibular disorders (TMD) of mainly myogenous origin. Methods: A randomized, controlled trial was performed with 60 patients suffering from myofascial pain. Patients were randomly assigned to a treatment or a control group. The treatment group was treated by means of a stabilization appliance and the control group by means of a non-occlusal appliance. Symptoms and signs were registered before and after 10 weeks of treatment. Results: Improvement of overall subjective symptoms was reported in both groups, but significantly more often in the treatment group than in the control group (P = .000). The prevalence of daily or constant pain showed a significant reduction in the treatment group (P = .028) compared with the control group. There was a significant decrease in the number of tender masticatory muscles in the treatment group (P = .018) compared with the control group. Conclusion: The results of this short-term evaluation suggest that the stabilization appliance is more effective in alleviating symptoms and signs in patients with TMD of mainly myogenous origin than a control, non-occlusal appliance. The stabilization appliance can therefore be recommended for the therapy of these patients. Keywords: stabilization appliance, randomized controlled trial, temporomandibular disorders, myofascial pain

Aims: To investigate alteration of ß2-adrenergic receptor (ß2AR) function in chronic localized myalgia subjects by evaluating levels of the ß2AR second messenger, cyclic adenosine monophosphate (cAMP), in mononuclear cells after ßAR-agonist stimulation. Methods: Eleven chronic localized myalgia subjects and 21 matched healthy controls participated in this study. Peripheral blood (30 cc) was drawn from the subjects' anterocubital vein. Mononuclear cells were isolated from the total blood by using the Ficoll-Hypaque gradient technique. Basal and stimulated intracellular cAMP levels were determined by enzyme immunoassay using a commercially available kit. Aliquots of 5 x 10 6 cells were incubated with or without stimulation of the ßAR-agonist isoproterenol for 5 minutes. Five different concentrations of isoproterenol (10-3M to 10-7M) were utilized. cAMP levels in both groups were tested statistically by a 2-way repeated-measures ANOVA with 2 predictors, group difference and isoproterenol concentration difference. As with isoproterenol stimulation, the cAMP responses to forskolin, which activates adenylyl cyclase directly and produces cAMP, bypassing the cell surface receptors were also measured. Results: The basal cAMP levels in both groups (myalgia: 0.33 ± 0.02 pmol/5 x 10 6 cells; control: 0.43 ± 0.10 pmol/5 x 10 6 cells) were almost identical, and isoproterenol-produced cAMP levels increased dose-dependently in both groups. No significant differences in the mean cAMP levels were observed between the groups (P = .909). Significant increases were observed according to the isoproterenol concentration increase (P .0001). The cAMP responses to forskolin stimulation also showed no significant group difference (P = .971). Conclusion: These results suggest that ß2AR function is not different between localized myalgia subjects and healthy individuals. Keywords: localized myalgia, ß2-adrenergic receptor, cAMP, mononuclear cell, isoproterenol

Aims: To develop and test a probe for measurement of the pressure pain threshold (PPT) over the posterior aspect of the temporomandibular joint (TMJ) in healthy individuals, including determination of PPT levels, reliability, and the smallest detectable difference (SDD) between measurements. Methods: A semi-spherical probe was designed to measure PPT levels over the posterior aspect of the TMJ through the external auditory meatus. The probe was connected to an electronic algometer. Three consecutive measurements were performed with this probe over the posterior and lateral aspects of the left and right TMJs as well as over a reference point on the forehead (glabella) in 31 healthy subjects: 10 male and 21 female. Measurements were also performed for comparison with a conventional flat probe with a 1 cm2 area over the lateral aspect of the TMJ and the reference point. Results: The PPT measured with the semi-spherical probe and the conventional probe showed similar degrees of interindividual variation and reproducibility. The relative SDD, expressed as the percentage of the mean PPT for 2 measurements, showed similar levels for the flat and semi-spherical probes, ie, 28% to 32% of the mean PPT at the TMJ. Conclusion: The semi-spherical probe shows similar reliability and relative SDD for measurement of PPT levels over the posterior aspect of the TMJ in healthy individuals as measurement over the lateral aspect with a flat probe. Measurement of the posterior PPT with a semi-spherical probe may be a useful adjunct to conventional lateral PPT measurements. Keywords: algometer probe, healthy, pressure pain threshold, smallest detectable difference, temporomandibular joint

Aims: To investigate a recently developed pain-intensity matching device (Painmatcher) in terms of reproducibility, pain intensity, and unpleasantness experienced by healthy individuals upon pain threshold assessment, as well as differences in pain threshold between genders and between healthy individuals and patients with acute oral pain, and the relation between pain-intensity assessments by the Painmatcher and a visual analog scale (VAS) in the patients. Methods: Forty healthy individuals and 28 patients with acute oral pain participated. The Painmatcher produces an eventually noxious stimulus by increasing electrical impulses between 2 fingers. Pain thresholds were assessed twice in the healthy individuals and the provoked pain intensity and unpleasantness were recorded on a VAS. In the patients, pain threshold and ongoing pain were assessed with the Painmatcher and the ongoing pain was recorded on a VAS. Results: Painmatcher scores for the 2 pain threshold assessments were equally correlated in the healthy individuals and patients. VAS scores for ongoing pain and pain caused by the Painmatcher when the ongoing pain intensity was assessed were positively correlated. In the healthy individuals, the degree of unpleasantness was higher than the pain intensity at the pain threshold. The patients had a lower pain threshold than the healthy individuals. Conclusion: This study indicates that patients with acute oral pain have lower Painmatcher pain thresholds than healthy individuals, suggesting a general decrease in nociceptive thresholds in these patients. The Painmatcher seems to be as valid as a VAS for acute oral pain assessment. The Painmatcher pain threshold is highly reproducible but associated with unpleasantness. Keywords: facial pain, pain, pain measurement, pain threshold, visual analog scale

Aims: To test for orthotropy in the stress-strain behavior of the temporomandibular joint (TMJ) disc under repeated physiologic loading before and after an impact event. Methods: Two groups, each consisting of 10 discs, were subjected to repeated tensile cycling in the dorsoventral (group 1) and mediolateral (group 3) direction. Two additional groups, each consisting of 10 discs, had preconditioning in the form of a 1.18 N·s impulsive load before tensile cycling in either the dorsoventral (group 2) or mediolateral (group 4) direction. Physiologic loads of 1 to 3 N were cycled at 0.1 Hz, and stress-strain responses were recorded every cycle between 1 to 10 cycles, and then periodically at 50, 100, 500, 750, and 1,000 cycles. The properties of elastic modulus, residual strain upon unloading, and area contained within the hysteresis loop were measured. Results: Dorsoventral loading produced 5-fold higher elastic modulus, 5-fold lower residual strain, and 5-fold lower hysteresis compared to mediolateral tensile loading (P = .001). Repeated loading effectively reduced the viscous response for all discs, as the elastic modulus increased while residual strain and hysteresis decreased. Impulsive loading caused elastic modulus to increase for dorsoventrally cycled discs, whereas hysteresis decreased for mediolaterally cycled discs (P = .05). Conclusion: The findings suggest that damage from the impact load may have increased the porosity of the extracellular matrix, which ultimately resulted in additional stress transfer to the collagen fibers during loading. Impulsive loads may be an important preconditioning factor in the fatigue failure of the TMJ disc in vivo. Keywords: fatigue, TMJ disc, cartilage, viscoelasticity, stress-strain