Daytime changes of salivary biomarkers involved in pain

Abstract

The study aimed to investigate salivary levels of nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), substance P (SP) and glutamate at five time points from morning to afternoon in a well‐characterised healthy and pain‐free individuals. Ten young adults were included. Unstimulated and stimulated whole saliva were collected from each participant repeatedly across the day. Blood samples were drawn in connection with the first and last saliva sample as reference standard. Levels of NGF and BDNF were determined using gel‐free Western blot technology, glutamate levels were analysed using a colorimetric assay, and SP was determined using a commercially available ELISA. Salivary NGF and BDNF showed significant differences between the different collection times in both unstimulated (NGF; P = .006; BDNF; P = .026) and stimulated whole saliva (NGF; P = .006; BDNF; P = .019). The highest concentrations of the neuropeptides were expressed in the early morning, and they thereafter decreased across the day. In contrast, the expression of salivary glutamate and SP did not show any significant changes across the day. Plasma levels of NGF were higher in the evening sample (P = .028); otherwise, there were no significant differences for any of the other markers between morning and evening samples. NGF and BDNF in whole saliva showed a significant variation across the day. On the contrary, no variation in the levels of SP and glutamate was detected. These findings highlight the importance of consistency in the collection time and approach in biomarker studies using saliva.

Altered levels of salivary and plasma pain related markers in temporomandibular disorders

“…We have previously shown that BDNF levels are lower in stimulated whole saliva compared to resting whole saliva, and consequently the salivary BDNF are affected by the flow rate. One may therefore speculate if the lower levels in patients could be a consequence of the slightly lower flow rate (Table 1) [49]. Plasma BDNF levels on the other hand, showed as expected higher levels in TMDmyalgia.…”

“…Several substances enter the salivary gland from the blood by passing through the intercellular spaces by transcellular or paracellular diffusion, consequently saliva is often regarded as an ultrafiltrate of plasma and contains fractions of proteins derived from the blood stream [42,49], which explains the usually lower concentration of NGF, BDNF and SP in saliva compared to plasma. Glutamate on the contrary showed higher levels in saliva, which imply a local secretion or even a diffusion from adjacent structures e.g.…”

Biomarcadores salivares na avaliação da dor: revisão integrativa

“…Por isso, observa-se um interesse crescente no diagnóstico salivar, visto que as glândulas salivares estão integradas ao sistema neuroendócrino e contêm uma grande variedade de moléculas que podem desempenhar papéis importantes na fisiopatologia da dor. (39,40) Muitos constituintes do plasma entram na saliva por difusão passiva, transporte ativo ou ultrafiltração extracelular. (41) Como resultado, a maioria das substâncias encontradas no sangue também estão presentes na saliva e, dessa forma, considera-se a saliva como funcionalmente equivalente ao soro, refletindo o estado fisiológico do organismo.…”

Salivary Alpha-Amylase in Experimentally-Induced Muscle Pain

“…However, pain intensity itself may not be a reliable tool for assessing pain, especially for pain in the orofacial region [ 42 , 43 ], since other factors seems to play an important role in the individual’s perception of the pain experience [ 44 ]. Several studies have shown that subjective pain level poorly correlate to several biomarkers shown to be related to pain [ 26 , 45 , 46 , 47 ], but rather to different variables such as physical and psychological functioning [ 42 , 43 , 48 , 49 , 50 ]. Therefore, the multidimensional experience of pain [ 51 ], including not only intensity, but also the cognitive and affective component, should be taken into consideration in further studies [ 52 , 53 , 54 , 55 , 56 ].…”

“…Saliva samples offer a non-invasive method in contrast to other sampling methods, e.g., blood or cerebrospinal fluid. These procedures might also be accompanied by anxiety or pain, which are stressors themselves [ 25 , 26 , 27 ]. Despite the advantages, there are a few drawbacks that need to be considered.…”