Abstract
BackgroundDifferent pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics.MethodsPatients diagnosed according to the diagnostic criteria for TMD (n = 39), and matched healthy pain-free controls (n = 39) were included. Stimulated whole saliva and plasma samples were collected in the morning. Glutamate was analysed using a colorimetric assay, and 5-HT and SP were analysed by commercially available ELISA. Levels of NGF and BDNF were determined using multiplex electrochemiluminescence assay panel.ResultsPatients expressed higher salivary and plasma levels of glutamate (saliva: 40.22 ± 13.23 μmol/L; plasma: 30.31 ± 18.73 μmol/L) than controls (saliva: 33.24 ± 11.27 μmol/L; plasma: 20.41 ± 15.96 μmol/L) (p < 0.05). Salivary NGF (0.319 ± 0.261 pg/ml) and BDNF (3.57 ± 1.47 pg/ml) were lower in patients compared to controls (NGF: 0.528 ± 0.477 pg/ml; BDNF 4.62 ± 2.51 pg/ml)(p’s < 0.05). Contrary, plasma BDNF, was higher in patients (263.33 ± 245.13 pg/ml) than controls (151.81 ± 125.90 pg/ml) (p < 0.05). 5-HT was undetectable in saliva. Neither plasma 5-HT, nor SP levels differed between groups. BDNF and NGF concentrations correlated to levels of psychological distress (p < 0.0005).ConclusionThe higher levels of salivary and plasma glutamate in patients with TMD-myalgia compared to controls strengthens its importance in the pathophysiology of TMD-myalgia. However, the lack of correlation to pain levels question its role as a putative biomarker. Patients with TMD-myalgia further had lower levels of salivary NGF and BDNF, but higher plasma BDNF. These results and their correlations to psychological distress warrant further investigations.
Highlights
Different pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample
Even if the levels were significantly higher in patients compared to controls, the patients expressed on average mild depressive symptoms and insomnia, moderate levels of somatic symptoms and perceived stress, and almost no clinically relevant pain catastrophizing (Table 1)
Male temporomandibular disorder (TMD) patients had higher levels of salivary glutamate compared to female patients (t = − 3.022; = 36; p = 0.005), but there were no sex differences in plasma levels
Summary
Different pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics. The role of central mechanisms seems to be more evident the longer the pain persists, but peripheral inputs are believed to drive the pain [5, 7]. There is increasing evidence for neurogenic derived inflammation in TMD-myalgia [6, 8]. These mechanisms involve release of neuropeptides by activation of peripheral sensory afferent neurons. These neuropeptides promotes in turn the release of other chemicals that continues to activate and sensitize neurons [6]
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