Age differences in salivary markers of inflammation in response to experimental pain: does venipuncture matter?

Abstract

An important consideration in mechanistic research using biomarkers should include the use of saliva as an alternative to blood. The use of saliva would allow the study of susceptible populations such as older adults where venipuncture may not be feasible. Although saliva has been most commonly used to measure cortisol and tumor necrosis factor-α (TNFα), there is limited evidence that other cytokines found in saliva significantly change in response to laboratory-induced pain. Therefore, the aim of the current preliminary study was to characterize the time course, duration and magnitude of changes of commonly measured pro- (interleukin [IL]-6, IL-8) and anti-inflammatory (IL-10, IL-4) cytokines in saliva samples and to test for age-related differences in separate experimental painful and non-painful control sessions. In addition, we also tested whether venipuncture results in significant cytokine alterations similar to a painful stimulus in a non-painful, non-venipuncture control session. All cytokines were significantly induced by the cold pressor task compared to a warm control session (p < 0.001). Specifically, healthy older adults experienced greater salivary changes in all cytokines during the cold pressor session compared to younger adults in the non-painful sessions (p < 0.001). There were no significant differences between the venipuncture and non-venipuncture sessions across all cytokines (p > 0.05). Our findings support the use of saliva as a substitute for blood in both young and older healthy individuals to measure changes after experimental pain stimulation. In addition, venipuncture alone is not sufficient to induce IL-6, IL-8, IL-10 and IL-4. Future studies in the community are urgently needed to validate and further move translational mechanistic pain research to those populations most underrepresented in clinical research.

Saliva as a medium to detect and measure biomarkers related to pain

“…Whereas a recent study has suggested marginal differences in several inflammatory cytokines between young and elderly participants. In our study however, age could not further be examined because of the limited age-interval 28 . Nevertheless, we could demonstrate a significant association between stimulation of salivary flow and NGF expression.…”

“…Since it is not clear whether the menstrual cycle affects the salivary response and salivary flow we did not control for menstrual cycle variations. Further, according to some findings age may affects protein expression 35 but a recent study have shown negligible differences in inflammatory markers in young and elderly individuals 28 . A limited age interval was however used in the current study design to minimise a possible confounder.…”

Profiling the Salivary microbiome of the Qatari population

“…Proteolytic bacteria such as Prevotella are known to degrade proteins and peptides and are associated with periodontitis [28,58]. It is known that the saliva composition changes with age due to the slower salivary flow [59], inadequate oral care, increase of several inflammatory mediators [60], systemic diseases and other additional environmental factors that together will affect the microbial composition in the saliva [28,61]. The adult salivary microbial population this cohort was more diverse including microbes like Streptococcus, Haemophilus, Rothia and Veillonella and Lautrophia, some are known to degrade carbohydrates [50].…”

Diagnostic value of salivary CRP and IL-6 in patients undergoing anti-TNF-alpha therapy for rheumatic disease

“…Composition of human saliva depends both on systemic and local factors (Khan et al 2017 ). Thus, it may reflect pathophysiological processes relevant to the development both of systemic and local disease (Abdul Rehman et al 2017 ; Buczko et al 2015 ; Cruz-Almeida et al 2017 ). In this respect, saliva has been used as a diagnostic tool to aid the assessment of periodontal disease activity (Korte and Kinney 2016 ; Podzimek et al 2016 ).…”