| Ozdogan et al., 2019 Turkey(10)
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N = 39
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Adults ≥ 18 years
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Cross-sectional
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Level of evidence VI
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To determine the concentration of salivary opiorphin in dental pain. |
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Salivary opiorphin levels increase in dental pain. A strong correlation was observed between the level of pain reported by the individual and salivary opiorphin levels. It was also observed that the extent of inflammation affects opiorphin levels. |
| Shaw et al., 2018 India(20)
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To assess cortisol levels before and after a session of motor physical therapy in newborns. |
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No difference in salivary cortisol was found after motor physical therapy. The PIPP score increased after motor physical therapy, but pharmacological intervention was not needed. Motor physical therapy was well tolerated and did not result in stress for the newborn. |
| Silva Andrade et al., 2018 Brazil(9)
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To assess the levels of stress-related salivary biomarkers in patients in orthodontic treatment with fixed brackets, comparing these patients with individuals with normal mastication. |
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It was observed that orthodontic patients showed a significant increase in emotional stress, detected by alpha-amylase activity after the arch wire placement, when the patients reported the highest pain scores. Baseline salivary cortisol was not affected by the treatment and the use of isolated endocrine measures is not adequate to predict temporary pain in patients under orthodontic treatment. No stress-related biomarkers were correlated to the pain reports. |
| Jenkins et al., 2018 USA(21)
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To assess strategies of emotional regulation and positive affection in children with cancer exposed to a painful experimental procedure (cold pressor task). |
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Specific strategies of emotional regulation, such as distraction and reassessment, can mitigate the response to stress and pain in pediatric patients with cancer and modulate salivary sAA levels. The study points out that reports of behavioral pain do not always correspond to the physiological response. |
| Yennurajalingam et al., 2018 USA(22)
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To determine the viability and effectiveness of stimulation by cranial electrotherapy in depression, anxiety, sleep disorders, and pain scores in patients with late-stage cancer. |
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Cortisol, alpha-amylase (sAA), C-reactive protein (CRP), interleukin-1β (IL-1β), and interleukin-6 (IL-6)
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Brief Pain Inventory (BPI)
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No significant changes were found in salivary levels of cortisol, alpha-amylase, CRP, IL-1β, and IL-6 after four weeks of stimulation by cranial electrotherapy. The use of stimulation by cranial electrotherapy is associated with improvements in depression, anxiety scores, and pain severity. |
| Kollmann et al., 2017 Austria(23)
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To investigate the impact of early skin-to-skin contact after a cesarean section on the adaptation of the newborn, on maternal pain, and on the response to stress. |
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Salivary levels of cortisol and alpha-amylase, well-being (reports of intraoperative nausea and vomiting), and maternal pain showed no difference between the groups with early and late skin-to-skin contact. |
| Sobas et al., 2016 Spain(24)
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N = 34
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Adults
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30 to 40 years
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Observational
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Level of evidence VI
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To assess the variability of potential biomarkers for pain assessment. |
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Cortisol, alpha-amylase (sAA), immunoglobulin A (sIgA), testosterone, and tumor necrosis factor alpha receptor II (sTNFαRII)
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Numeric rating scales (NRS)
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It was observed that sIgA and sTNFαRII presented acceptable reproducibility levels in healthy individuals and can be used as potential salivary biomarkers to assess pain. |
| Wittwer et al., 2016 Switzerland(25)
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To investigate the effects of acute pain caused by heat on salivary alpha-amylase activity. |
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A positive correlation was observed between alpha-amylase levels and the intensity of pain in response to painful stimuli by heat. It is suggested that alpha-amylase is a physiological indicator of painful perception resulting from heat. |
| Kim et al., 2016 South Korea(26)
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To assess psychological stress and the activation of the stress system in patients with rheumatoid arthritis. |
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Cortisol levels were higher in patients with rheumatoid arthritis. No difference was found in alpha-amylase levels. The results suggest that depression is more prevalent in patients with rheumatoid arthritis in comparison with the control group. This may be related to the subjective symptoms of pain, because a positive correlation was observed between scores in the Beck Depression Inventory (BDI) and in the VAS for pain. |
| Symons et al., 2015 USA(8)
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To assess the viability of magnetic resonance and immunoassays to identify and compare relevant salivary biomarkers in pediatric patients with cerebral palsy, with and without pain. |
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Cytokines, chemokines, hormones, and neuropeptides.
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Dalhousie Pain Interview (DPI)
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It was observed that the levels of most salivary metabolites, neuropeptides, cytokines, and hormones were higher in children with cerebral palsy with pain (based on the parents’ previous report) versus without pain. |
| Generaal et al., 2014 The Netherlands(27)
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N = 1125
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Adults
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Cross-sectional
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Level of evidence VI
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To assess whether hypothalamic-pituitary-adrenal axis dysfunction is associated to the presence and severity of chronic musculoskeletal pain. |
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Cortisol
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Chronic pain grade (CPG)
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Low blood cortisol levels were observed in chronic musculoskeletal pain. The authors concluded that when chronic pain occurs together with a depressive or anxiety disorder, cortisol levels are masked. |
| Brown et al., 2014 Australia(7)
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To establish whether salivary cortisol and alpha-amylase are sensitive to the detection of stress during treatment procedures for burn wounds. |
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Cortisol and alpha-amylase (sAA)
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Revised Faces Pain Scale (FPS-R); Visual Analog Scale-Anxiety (VAS-A); Face, Legs, Arms, Cry, Consolability (FLACC) scale; Child Trauma Screening Questionnaire (CTSQ)
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Cortisol and alpha-amylase respond to stress from the procedures for treating burn wounds. Alpha-amylase levels were associated to pain and to high CTSQ scores. The authors indicate that cortisol and alpha-amylase can be used to assess stress and pain during the placement of dressings in the treatment of burns. |
| Cabral et al., 2013 Brazil(28)
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N = 55
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Newborns, 30 weeks to 39 weeks and 5 days
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Observational, prospective
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Level of evidence VI
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To assess the response of newborns to stress during hospitalization in a neonatal intensive care unit |
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It is believed that the salivary concentration of cortisol is an indicator of neonatal stress, due to the adrenal response to stress during the first days of hospitalization. During the analysis of facial activity to assess acute pain, none of the children presented signs of pain, but this does not mean that the children were not under stress. |
| Shibata et al., 2013 Japan(29)
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To determine whether salivary biomarkers can be objective indicators of pain in newborns. |
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Significantly increased NIPS scores are reported after a painful procedure. Despite the changes in salivary biomarkers (sCgA or sAA) before and after a heel puncture, a large inter- and intra-subject variability was observed. The authors concluded that these biological indicators are not adequate to assess pain in newborns. |
| Ferrara et al., 2013 Italy(30)
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To assess the perception of pain in epileptic children during an invasive procedure (a puncture to collect venous blood) by determining salivary alpha-amylase activity and comparing it to the activity in healthy children. |
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It was observed that children with epilepsy present higher levels of alpha-amylase and greater sensitivity to pain when compared to the control group. A correlation was observed between sAA activity and PPP. The authors indicated that alpha-amylase activity may represent a new, objective, noninvasive biomarker to assess the perception of pain in children with epilepsy. |
| Robles et al., 2012 USA(31)
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N = 76
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Adults 18 to 40 years
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Prospective cohort
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Level of evidence IV
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To evaluate the clinical use of salivary alpha-amylase in assessing responses to the stress related to elective third molar tooth extraction. |
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It was observed that sAA levels were lower during the surgery and postoperative follow-up when compared to the levels measured before surgery. Although sAA did not present the increase expected by the authors, a relationship was observed between the response to pain and increased sAA levels. It was also observed that PCS scores were not significantly correlated to pain. |
| Goodin et al., 2012 USA(32)
|
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To assess whether hypnosis directly influences the hypothalamic-pituitary-adrenal axis and the proinflammatory reactivity to experimental acute pain (cold pressor task) |
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Hypnosis was associated to a reduction in the pain scores when compared to the control group. However, it was not associated to significant changes in cortisol and TNFα levels. |
| Campos et al., 2011 Brazil(33)
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To assess the correlation between salivary alpha-amylase levels and the intensity of the pain reported by the patients during an orthodontic treatment of bracket bonding and arch wire insertion. |
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No correlation was found between sAA concentrations and pain intensity in patients undergoing orthodontic treatment. However, the patients did present a significant, progressive increase of sAA levels during the evaluation period of 21 days, divided into three phases: pretreatment (days 1 to 7), bonding (days 8 to 14), and initial arch wire insertion (days 15 to 21). |
| Kiefte-de Jong et al., 2011 The Netherlands(34)
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N = 483
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Children
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14 to 24 months
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Prospective cohort
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Level of evidence IV
|
To assess whether the cortisol circadian rhythm and reactivity to stress are associated to functional constipation and abdominal pain in infancy. |
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Cortisol
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Abdominal Pain Index
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No difference was found in the cortisol circadian rhythm between children with and without constipation and abdominal pain. |
| Rodríguez de Sotillo et al., 2011 USA(35)
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N = 30
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Adults
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Case-control
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Level of evidence IV
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To determine whether oxidative stress biomarkers measured in the saliva and serum in patients with temporomandibular disorders (TMD) may be associated to increased pain when compared to a healthy control group. |
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8-hydroxy-2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant status (TAS)
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Pain Intensity (PI) score
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Salivary levels of 8-OHdG, MDA, and TAS were observed to be both changed and correlated to the respective serum levels in patients with TMD when compared to the control patients. Additionally, these salivary biomarkers were diagnostic predictors of pain severity. A significant association was observed between pain and salivary oxidative biomarkers in patients with TMD. |
| Mirrielees et al., 2010 USA(36)
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To test the hypothesis that rheumatoid arthritis influences salivary biomarker levels in periodontal disease. |
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Interleukin-1β (IL-1β), tumor necrosis factor alpha (TNFα), and metalloproteinase 8 (MMP8)
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Visual Analog Scale (VAS)
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Salivary IL-1β and TNFα levels were found to be significantly higher in patients with rheumatoid arthritis who were not treated with anti-TNFα antibodies when compared to patients treated with anti-TNFα and to healthy controls. It was concluded that salivary levels of IL-1β, MMP8, and TNFα are clearly influenced by the periodontal environment and by systemic inflammatory conditions such as rheumatoid arthritis. |
| Buğdaycı et al., 2010 Turkey(37)
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To investigate salivary alpha-amylase levels as a noninvasive tool to assess sympathetic nervous system activity in patients with migraine during attack, post-attack, and headache interval periods. |
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Changes in sAA levels were observed in different periods of migraine. No significant differences in sAA levels were found between the interval periods and the control group. It was observed that VAS scores were not correlated to sAA values obtained during migraine attack periods. |
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