Effects of Acute Experimental Stress on Pain Sensitivity and Cortisol Levels in Healthy Participants: A Randomized Crossover Pilot Study.

AIMS: To investigate pain sensitivity in the masseter muscle and index finger in response to acute psychologic stress in healthy participants. METHODS: Fifteen healthy women (23.7 ± 2.3 years) participated in two randomized sessions: in the experimental stress session, the Paced Auditory Serial Addition Task (PASAT) was used to induce acute stress, and in the control session, a control task was performed. Salivary cortisol, perceived stress levels, electrical and pressure pain thresholds (PTs), and pain tolerance levels (PTLs) were measured at baseline and after each task. Mixed-model analysis was used to test for significant interaction effects between time and session. RESULTS: An interaction effect between time and session occurred for perceived stress levels (P < .001); perceived stress was significantly higher after the experimental task than after the control task (P < .01). No interaction effects occurred for salivary cortisol levels, electrical PTs, or pressure PTLs. Although significant interactions did occur for electrical PTL (P < .05) and pressure PT (P < .001), the simple effects test could not identify significant differences between sessions at any time point. CONCLUSION: The PASAT evoked significant levels of perceived stress; however, pain sensitivity to mechanical or electrical stimuli was not significantly altered in response to the stress task, and the salivary cortisol levels were not altered in response to the PASAT. These results must be interpreted with caution, and more studies with larger study samples are needed to increase the clinical relevant understanding of the pain mechanisms and psychologic stress.

The effect of botulinum toxin A on patients with persistent idiopathic dentoalveolar pain-A systematic review.

BACKGROUND: It has been suggested that botulinum toxin A (BONT-A) is a safe and effective treatment in relieving pain in patients with persistent idiopathic dentoalveolar pain (PIDP). OBJECTIVES: This study aimed to systematically evaluate all the available studies investigating the pain-relieving effects of BONT-A in patients with PIDP. METHODS: A systematic search with specific search terms was made in PubMed, Web of Science and Scopus. Two authors screened titles and abstracts and selected eligible studies for inclusion in the systematic review. The quality of the studies was evaluated by the 12 items Quality Assessment Tool for Observational studies (Pre-Post) Studies with No Control Group, and the level of evidence was assessed according to GRADE. RESULTS: Three observational studies of 3695 identified were included (445 overlapping studies; 3247 excluded studies). All studies were uncontrolled observational studies investigating the pain-relieving effect of BONT-A in patients with PIDP. The included studies had a fair quality (moderate risk of bias) and insufficient level of evidence. The pain reducing effect by BONT-A injections was in average 50% or more in two studies, in one study 3 out of 4 patients became almost pain free. CONCLUSIONS: This systematic review shows that presently the level of scientific evidence is insufficient to evaluate the pain-relieving effect of BONT-A injections in patients with PIDP. There are indications that BONT-A injections could be a possible management option for patients with PIDP that seems to be safe and with few adverse events. There is a need for well-designed placebo-controlled, double-blind RCTs.

The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls.

Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p < 0.001), followed by a significant increase between 120 and 140 min (p < 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.

Effects of Low-Intensity Contractions of Different Craniofacial Muscles in Healthy Participants - An Experimental Cross-Over Study.

OBJECTIVE: Repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible, ie, bruxism, is traditionally linked to pain and unpleasantness in the active muscles. The aim of this study was to investigate the effects of standardized craniofacial muscle contractions on self-reported symptoms. METHODS: Sixteen healthy volunteers performed six 5-minute bouts of 20% maximal voluntary contraction task of the jaw-closing (Jaw), the orbicularis-oris (O-oris), and the orbicularis-oculi (O-oculi) muscles. Participants rated their perceived pain, unpleasantness, fatigue, and mental stress levels before, during, and after the contraction tasks on 0-10 Numeric Rating Scales (NRS). Each muscle contraction task (= 1 session) was separated by at least 1 week and the order of the sessions was randomized in each subject. RESULTS: All muscle contraction tasks evoked significant increases in NRS scores of pain (mean ± SD: Jaw; 3.8 ± 2.7, O-oris; 1.9 ± 2.2, O-oculi; 1.4 ± 1.3, P < .014), unpleasantness (Jaw; 4.1 ± 2.5, O-oris; 2.1 ± 1.9, O-oculi; 2.9 ± 1.8, P < .001), fatigue (Jaw; 5.8 ± 2.0, O-oris; 3.2 ± 2.3, O-oculi; 3.6 ± 1.9, P < .001), and mental stress (Jaw; 4.1 ± 2.1, O-oris; 2.2 ± 2.7, O-oculi; 2.9 ± 2.2, P < .001). The Jaw contractions were associated with higher NRS scores compared with the O-oris and the O-oculi contractions (P < .005) without differences between the O-oris and the O-oculi (P > .063). All symptoms disappeared within 1 day (P > .469). CONCLUSIONS: The results showed that submaximal static contractions of different craniofacial muscle groups could evoke transient, mild to moderate levels of muscle pain and fatigue and increased stress scores. The fatigue resistance may differ between different muscle groups. Further studies are warranted to better understand the contribution of specific craniofacial muscle groups for the characteristic presentation of musculoskeletal pain conditions in the head.

Dopamine in plasma - a biomarker for myofascial TMD pain?

BACKGROUND: Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. METHODS: Fifteen patients with M-TMD and 15 age- and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0-100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. RESULTS: Dopamine in plasma differed significantly between patients with M-TMD (4.98 ± 2.55 nM) and healthy controls (2.73 ± 1.24 nM; P < 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P < 0.001) and had lower PPTs (P < 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P < 0.05) and perceived mental stress (r = 0.34, n = 28, P < 0.05). CONCLUSIONS: The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.

Achieved Competencies and Satisfaction in Temporomandibular Disorders and Orofacial Pain Education.

AIMS: To assess dental students' achieved competencies and perceived satisfaction with their temporomandibular disorders (TMD) and orofacial pain education and to compare these with the results of their final examination in TMD and orofacial pain. METHODS: Dental students from two consecutive classes (2011/2012 and 2012/2013) at the Department of Orofacial Pain and Jaw Function at the dental school in Malmö, Sweden completed two self-evaluations, one at the beginning of semester seven and one at the end of semester eight. The questionnaire that they were given concerned achieved competencies and satisfaction with education in TMD and orofacial pain. Items focused on anatomy, physiology, and clinical training. Students estimated their competence and satisfaction on a numeric rating scale and described their idea of treating TMD and orofacial pain patients on a verbal rating scale. Outcome variables were tested with paired samples t test for differences over time and independent samples t test for between-class comparisons; both were adjusted for multiple testing with Bonferroni correction. RESULTS: Significant improvement in all items was observed for achieved competencies and satisfaction in both classes between semester seven and semester eight (P < .05). No differences in competencies or satisfaction occurred between classes at the end of the clinical course in semester eight (P > .05). CONCLUSION: This study has shown that expansion in undergraduate TMD and orofacial pain education at the dental school in Malmö has allowed all students to develop the same level of competence, independent of prior experience. The study also pointed out that continuous evaluation and enhancement of TMD and orofacial pain education in undergraduate dental education is beneficial.

Effects of experimental tooth clenching on pain and intramuscular release of 5-HT and glutamate in patients with myofascial TMD.

OBJECTIVES: It has been suggested that tooth clenching may be associated with local metabolic changes, and is a risk factor for myofascial temporomandibular disorders (M-TMD). This study investigated the effects of experimental tooth clenching on the levels of 5-HT, glutamate, pyruvate, and lactate, as well as on blood flow and pain intensity, in the masseter muscles of M-TMD patients. METHODS: Fifteen patients with M-TMD and 15 pain-free controls participated. Intramuscular microdialysis was performed to collect 5-HT, glutamate, pyruvate, and lactate and to assess blood flow. Two hours after the insertion of a microdialysis catheter, participants performed a 20-minute repetitive tooth clenching task (50% of maximal voluntary contraction). Pain intensity was measured throughout. RESULTS: A significant effect of group (P<0.01), but not of time, was observed on 5-HT levels and blood flow. No significant effects of time or group occurred on glutamate, pyruvate, or lactate levels. Time and group had significant main effects on pain intensity (P<0.05 and <0.001). No significant correlations were identified between: (1) 5-HT, glutamate, and pain intensity; or between (2) pyruvate, lactate, and blood flow. DISCUSSION: This experimental tooth clenching model increased jaw muscle pain levels in M-TMD patients and evoked low levels of jaw muscle pain in controls. M-TMD patients had significantly higher levels of 5-HT than controls and significantly lower blood flow. These 2 factors may facilitate the release of other algesic substances that may cause pain.

Effect of experimental tooth clenching on the release of ß-endorphin.

AIMS: To investigate the association between experimental tooth clenching and the release of ß-endorphin in patients with myofascial temporomandibular disorders (M-TMD) and healthy subjects. METHODS: Fifteen M-TMD patients and 15 healthy subjects were included and assigned an experimental tooth-clenching task. Venous blood was collected and pain intensity was noted on a visual analog scale. The masseter pressure pain threshold (PPT) was assessed 2 hours before the clenching task and immediately after. A mixed-model analysis of variance was used for statistical analyses. RESULTS: Significant main effects for time and group were observed for pain intensity and PPT, with significantly lower mean values of pain intensity (P < .001) and PPT (P < .01) after the clenching task compared with baseline. M-TMD patients had significantly higher pain intensity (P < .001) and significantly lower PPT (P < .05) than healthy subjects. No significant time or group effects were observed for the level of ß-endorphin. Neither pain intensity nor PPT correlated significantly with ß-endorphin levels. CONCLUSION: This experimental tooth-clenching task was not associated with significant alterations in ß-endorphin levels over time, but with mechanical hyperalgesia and low to moderate levels of pain in healthy subjects and M-TMD patients, respectively. More research is required to understand the role of the ß-endorphinergic system in the etiology of M-TMD.

Pain and intramuscular release of algesic substances in the masseter muscle after experimental tooth-clenching exercises in healthy subjects.

AIMS: To investigate whether experimental tooth clenching leads to a release of algesic substances in the masseter muscle. METHODS: Thirty healthy subjects (16 females, 14 males) participated. During two sessions, separated by at least 1 week, intramuscular microdialysis was performed to collect masseter muscle 5-hydroxytryptamine (5-HT) and glutamate as well as the metabolic markers pyruvate and lactate. Two hours after the start of microdialysis, participants were randomized to a 20-min repetitive experimental tooth-clenching task (50% of maximal voluntary contraction) or a control session (no clenching). Pain and fatigue were measured throughout. The Friedman and Wilcoxon tests were used for statistical analyses. RESULTS: No alterations were observed in the concentrations of 5-HT, glutamate, pyruvate, and lactate over time in the clenching or control session, or between sessions at various time points. Pain (P < .01) and fatigue (P < .01) increased significantly over time in the clenching session and were significantly higher after clenching than in the control session (P < .01). CONCLUSION: Low levels of pain and fatigue developed with this experimental tooth-clenching model, but they were not associated with an altered release of 5-HT, glutamate, lactate, or pyruvate. More research is required to elucidate the peripheral release of algesic substances in response to tooth clenching.

Development of a quality-assessment tool for experimental bruxism studies: reliability and validity.

AIMS: To combine empirical evidence and expert opinion in a formal consensus method in order to develop a quality-assessment tool for experimental bruxism studies in systematic reviews. METHODS: Tool development comprised five steps: (1) preliminary decisions, (2) item generation, (3) face-validity assessment, (4) reliability and discriminitive validity assessment, and (5) instrument refinement. The kappa value and phi-coefficient were calculated to assess inter-observer reliability and discriminative ability, respectively. RESULTS: Following preliminary decisions and a literature review, a list of 52 items to be considered for inclusion in the tool was compiled. Eleven experts were invited to join a Delphi panel and 10 accepted. Four Delphi rounds reduced the preliminary tool-Quality-Assessment Tool for Experimental Bruxism Studies (Qu-ATEBS)- to 8 items: study aim, study sample, control condition or group, study design, experimental bruxism task, statistics, interpretation of results, and conflict of interest statement. Consensus among the Delphi panelists yielded good face validity. Inter-observer reliability was acceptable (k = 0.77). Discriminative validity was excellent (phi coefficient 1.0; P < .01). During refinement, 1 item (no. 8) was removed. CONCLUSION: Qu-ATEBS, the seven-item evidence-based quality assessment tool developed here for use in systematic reviews of experimental bruxism studies, exhibits face validity, excellent discriminative validity, and acceptable inter-observer reliability. Development of quality assessment tools for many other topics in the orofacial pain literature is needed and may follow the described procedure.

Experimental tooth clenching. A model for studying mechanisms of muscle pain.

The overall goal of this thesis was to broaden knowledge of pain mechanisms in myofascial temporomandibular disorders (M-TMD). The specific aims were to: Develop a quality assessment tool for experimental bruxism studies (study I). Investigate proprioceptive allodynia after experimental tooth clenching exercises (study II). Evaluate the release of serotonin (5-HT), glutamate, pyruvate, and lactate in healthy subjects (study III) and in patients with M-TMD (study IV), after experimental tooth clenching exercises. In (I), tool development comprised 5 steps: (i) preliminary decisions, (ii) item generation, (iii) face-validity assessment, (iv) reliability and discriminative validity testing, and (v) instrument refinement. After preliminary decisions and a literature review, a list of 52 items to be considered for inclusion in the tool was generated. Eleven experts were invited to participate on the Delphi panel, of which 10 agreed. After four Delphi rounds, 8 items remained and were included in the Quality Assessment Tool for Experimental Bruxism Studies (Qu-ATEBS). Inter-observer reliability was acceptable (k = 0.77), and discriminative validity high (phi coefficient 0.79; P < 0.01). During refinement, 1 item was removed; the final tool comprised 7 items. In (II), 16 healthy females participated in three 60-min sessions, each with 24- and 48-h follow-ups. Participants were randomly assigned to a repetitive experimental tooth clenching task with a clenching level of 10%, 20%, or 40% of maximal voluntary clenching force (MVCF). Pain intensity, fatigue, perceived intensity of vibration (PIV), perceived discomfort (PD), and pressure pain threshold (PPT) were measured throughout. A significant increase in pain intensity and fatigue but not in PD was observed over time. A significant increase in PIV was only observed at 40 min, and PPT decreased significantly over time at 50 and 60 min compared to baseline. In (III), 30 healthy subjects (16 females, and 14 males) participated in two sessions at a minimum interval of 1 wk. Microdialysis was done to collect 5-HT, glutamate, pyruvate, and lactate and to measure masseter muscle blood flow. Two hours after the start of microdialysis, participants were randomized to a 20-min repetitive experimental tooth clenching task (50% of MVCF) or a control session (no clenching). Pain intensity was measured throughout the experiment. Substance levels and blood flow were unaltered at all time points between sessions, and between genders in each session. Pain intensity was significantly higher after clenching in the clenching session compared to the same time point in the control session. In (IV), 15 patients with M-TMD and 15 healthy controls participated in one session and the methodology described above was used. M-TMD patients had significantly higher levels of 5-HT and significantly lower blood flows than healthy controls. No significant differences for any substance at any time point were observed between groups. Time and group had significant main effects on pain intensity. Qu-ATEBS, the 7-item evidence-based quality assessment tool, is reliable, exhibits face-validity, and has excellent discriminative validity. Tooth clenching was associated with pain, fatigue, and short-lasting mechanical hyperalgesia, but not with proprioceptive allodynia. It seems that tooth clenching is not directly related to delayed onset muscle soreness. In healthy subjects and in patients with M-TMD, levels of 5-HT, glutamate, pyruvate, and lactate were unaltered after tooth clenching. But 5-HT levels were significantly higher and blood flows significantly lower in M-TMD patients than in healthy controls at all time points. These two factors may facilitate the release, and enhance the effects, of other algesic substances that may cause pain.

Assessment of proprioceptive allodynia after tooth-clenching exercises.

AIMS: To (A) evaluate test-retest reliability of vibrotactile sensitivity in the masseter muscle and (B) test if (1) the vibration threshold is decreased after experimental tooth clenching, (2) intense vibrations exacerbate pain after tooth clenching, (3) pain and fatigue are increased after tooth clenching, and (4) pressure pain thresholds are decreased after tooth clenching. METHODS: In part A, 25 healthy female volunteers (mean age: 42 ± 12 years) participated, and 16 healthy females (mean age 32 ± 10 years) participated in three 60-minute sessions, each with 24- and 48-hour follow-ups in part B. Participants were randomly assigned tooth-clenching exercises with clenching levels of 10%, 20%, or 40% of maximal voluntary clenching. A Vibrameter applied to the right masseter muscle measured perceived intensity of vibration and perceived discomfort, which were assessed on 0-50-100 numeric rating scales. An electronic algometer measured pressure pain threshold (PPT). Two 0- to 100-mm visual analog scales measured pain intensity (VASpain) and fatigue (VASfatigue). Measurements were made on the right masseter muscle. Interclass correlation coefficient (ICC) was used to calculate test-retest reliability of VT measurements. Outcome variables were tested with two-way ANOVAs for repeated measures and Dunnett's post-hoc test. RESULTS: Moderate long-term (ICC 0.59) and good short-term (ICC 0.92) reliability was found for VT on the masseter muscle. Clenching level had no main effect on perceived intensity of vibration; time effects (P < .05) were only observed at 40 minutes (Dunnett's test: P < .01). Clenching level and time had no effect on perceived discomfort. Only time effects were significant for PPT (P < .01), with reductions at 50 and 60 minutes compared to baseline (Dunnett's test: P < .05). Clenching level and time had main effects for VASpain and VASfatigue (P < .001). CONCLUSION: Experimental tooth clenching appears to evoke moderate levels of pain and fatigue and short-lasting hyperalgesia to mechanical stimulation, but not proprioceptive allodynia. The absence of proprioceptive allodynia does not necessarily exclude delayed onset muscle soreness (DOMS) but warrants further studies on the clinical manifestations of DOMS in jaw muscles.