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.

Inflammatory Cytokines and Sleep Disturbance in Patients with Temporomandibular Disorders.

AIMS: To assess the degree and interrelationship of sleep disturbance and plasma cytokine levels in temporomandibular disorder (TMD) pain patients. METHODS: Forty female TMD patients and 20 age-, sex-, and body mass index (BMI)-matched healthy subjects were enrolled. TMD was diagnosed using the Research Diagnostic Criteria for TMD. The TMD patients were classified as having low or high disability according to Graded Chronic Pain Scale findings. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality. Plasma concentrations of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured from blood samples collected between 9 am and noon. Statistical analyses included Kruskal-Wallis and one-way analysis of variance tests to compare results between different groups and multivariate general linear models to evaluate the effect of sleep status on cytokine levels. RESULTS: The high-disability group had the highest PSQI and ESS scores (P < .001). Plasma levels of IL-1ß, IL-6, IL-10, and TNF-α were significantly higher in the patient groups, with the high-disability group exhibiting the highest values (P ≤ .001). The plasma cytokine levels were significantly correlated with PSQI scores (P < .05). Plasma levels of IL-10 and TNF-α were significantly associated with the disability level after adjusting for both sleep indices (both P < .05). CONCLUSION: Patients with TMD, especially those with high disability, had elevated plasma cytokine levels and increased ESS and PSQI scores suggestive of sleep disturbance.

High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome.

BACKGROUND: Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. GOALS: To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. STUDY: This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. RESULTS: A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not. CONCLUSIONS: Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.

[Features of the hormonal status in patients with temporomandibular joint dysfunction and class II malocclusion].

The article presents data on androgen levels in female patients with temporomandibular joint (TMJ) dysfunction of varying degree and class II malocclusion. The study revealed significant correlation between degenerative and inflammatory TMJ changes and androgens level in patients with stigmas of connective tissue dysplasia (p<0.05), probably due to indirect proinflammatory action of androgens as they stimulate inflammatory mediators expression.

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.

A cross-sectional study of the relationship between serum sexual hormone levels and internal derangement of temporomandibular joint.

Temporomandibular disorders (TMD) are defined as clinical conditions that involve the masticatory muscles, temporomandibular joint (TMJ) or both. The aim of this study was to evaluate serum 17ß-oestradiol and progesterone levels in menstruating women affected by internal derangement of the TMJ. A total of 142 women (mean age 30·2 ± 6·7) who referred to medical diagnostic laboratory of Iranian Academic Centre for Education, Culture and Research (ACECR), Mashhad Branch, were enrolled during 2007 and 2008. Forty-seven individuals had disc displacement with reduction (Group IIa) according to Research Diagnostic Criteria (RDC)/TMD Axis I diagnosis. Radioimmunoassay was used for the detection of serum 17ß-oestradiol and progesterone levels in all 142 subjects. The mean progesterone level was significantly higher in control group (11·6 ± 10·4 ng mL(-1) ) compared to women with TMD (8·4 ± 6·8 ng mL(-1) , P = 0·03). No significant difference was found in two groups regarding 17ß-oestradiol level. Lower progesterone level in women with TMD can suggest the more important role of this hormone in the development of the disorder.

Human temporomandibular joint and myofascial pain biochemical profiles: a case-control study.

Neurobiological mechanisms of human musculoskeletal pain are poorly understood. This case-control study tested the hypothesis that biomarkers within temporomandibular muscle and joint disorders (TMJD) subjects' masseter muscles or temporomandibular joint (TMJ) synovial fluid correlate with plasma biomarker concentrations. Fifty subjects were recruited and categorized into TMJD cases (n=23) and pain-free controls (n=27) at the University of Minnesota School of Dentistry. Prior to specimen collection, pain intensity and pressure pain threshold masseter muscles and the TMJs were assessed. We collected venous blood; biopsied masseter muscle; and sampled TMJ synovial fluid on the subjects' side of maximum pain intensity. We assayed these tissues for the presence of nerve growth factor (NGF), bradykinin (BK), leukotreine B(4) (LTB(4) ) and prostaglandin E(2) (PGE(2) ), F(2) -isoprostane (F(2) I) and substance P (SP). The data was analyzed using Spearman Correlation Coefficients. We found that only plasma concentrations of bradykinin statistically correlated with synovial fluid concentrations (ρ=-0·48, P=0·005), but no association was found between pain intensities. The data suggests that biomarkers used to assess TMJD need to be acquired in a site-specific manner. We also discovered that F(2) I concentrations were associated with muscle pain intensity and muscle pressure pain threshold (PTT) (ß=0·4, 95%CI: 0·03-0·8) and joint PPT (ß=0·4, 95%CI: 0·07-0·8) suggesting that muscle oxidative stress is involved in myofascial pain and that F(2) -I may be a biomarker for myofascial pain.

Basal circadian cortisol secretion in women with temporomandibular disorders.

Muscular temporomandibular disorder (TMD) is a common stress-related condition showing marked comorbidity with depression and fibromyalgia (FM), both of which are associated with dysregulation of cortisol secretion. We measured cortisol levels in 15 women with well-defined TMD and 15 matched controls by sampling blood at 10-minute intervals over 24 hours in a controlled environment. TMD patients showed markedly increased daytime cortisol levels 30% to 50% higher than those of controls (p = 0.0032) and a one-hour phase delay in the timing of maximum cortisol levels (p = 0.048). Increased activation of the stress hormone axis by conscious pain perception is a likely explanation, but the magnitude of the increase could indicate that pain in the facial region acts as a greater stimulus than pain elsewhere in the body.

[Steroidogenesis disorders in women with temporomandibular dysfunction]. / Narusheniia steroidogeneza u zhenshin s disfunktsiiami visochno-nizhnecheliustnogo sustava.

The aim of the study was to trace hormone shifts in women suffering from different manifestation of the TMJ pain dysfunction syndrome. Levels of some blood steroid hormones (oestradiol, progesterone, testosterone, cortisol) were determined in 193 female patients aged 14-70. The object of study was blood serum collected in different menstrual phases. It was found that when pain dysfunction syndrome of the TMJ was accompanied by intact dentition and orthognathic occlusion blood steroid levels demonstrated shifts since puberty. In pain dysfunction syndrome of the TMJ accompanied by occlusal disharmony steroid shifts were first registered an early reproductive age. In patients without pain dysfunction syndrome of the TMJ steroid values remained close to those of healthy control. Shifts in steroid production may be indicative of impaired steroidogenesis in women with pain dysfunction syndrome of the TMJ.

Pain, allodynia, and serum serotonin level in orofacial pain of muscular origin.

AIMS: This study was conducted to investigate the serum level of serotonin (S-5-HT) in patients with temporomandibular disorders (TMD) of muscular origin, i.e., localized myalgia, and to compare it to that found in healthy individuals and patients with fibromyalgia. A second aim was to investigate the association between S-5-HT and pain parameters. METHODS: Twenty patients with localized myalgia participated in the study. Twenty age- and gender-matched healthy individuals and twenty patients with fibromyalgia served as controls. The participants were examined clinically as to the condition of the temporomandibular region and S-5-HT. RESULTS: The levels of S-5-HT did not differ significantly between the groups. However, in patients with localized myalgia there was a negative correlation between S-5-HT and tenderness of the temporomandibular muscles. CONCLUSION: The results of this study indicate that allodynia of orofacial muscles in patients with TMD is significantly related to S-5-HT concentration.