Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment.

Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c.

We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen's effect size of 0.5 to 0.7.

This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.

Type 1 diabetes (T1D) is associated with general- and diabetes-specific stress which has multiple adverse effects. Hence measuring stress is of great importance. An algometer measuring pressure pain sensitivity (PPS) has been shown to correlate to certain stress measures in adults. However, it has never been investigated in children and adolescents. The aim of our study was to examine associations between PPS and glycated hemoglobin (HbA1c), salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D. Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits. Salivary cortisol, PPS and questionnaires were collected, measured, and answered on site. HbA1c was collected from medical files. We found correlations between PPS and HbA1c (rho = 0.35, P = 0.046), cortisol (rho = -0.25, P = 0.02) and Perceived Stress Scale (rho = -0.44, P = 0.02) in different subgroups based on age. Males scored higher in PPS than females (P < 0.001). We found PPS to be correlated to HbA1c but otherwise inconsistent in results. High PPS values indicated either measurement difficulties or hypersensibility towards pain.

Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke.

Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke.

We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group.

Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.

Autonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention.

The present study tested the role of cerebral regulation of ANSD as consequence of novel understanding of glucose metabolism and treatment target in type 2 diabetes (T2D), suggested by the claim that the pressure pain sensitivity (PPS) of the chest bone periosteum may be a measure of cerebral ANSD.

In a randomized controlled trial of 144 patients with T2D, we tested the claim that 6 months of this treatment would reduce PPS and improve peripheral glucose metabolism.

In the active treatment group, mean glycated hemoglobin A1c (HbA1c) declined from 53.8 to 50.5 mmol/mol (intragroup p = 0.001), compared with the change from 53.8 to 53.4 mmol/mol in the control group, with the same level of diabetes treatment but not receiving the active treatment (between group p = 0.036). Mean PPS declined from 76.6 to 56.1 units (p < 0.001) in the active treatment group and from 77.5 to 72.8 units (p = 0.02; between group p < 0.001) in the control group. Changes of PPS and HbA1c were correlated (r = 0.37; p < 0.001).

We conclude that the proposed approach to treatment of T2D is a potential supplement to conventional therapy.

www.clinicaltrials.gov (NCT03576430).

This randomized double-blind controlled study aimed to investigate the effects of a standardized Kaempferia parviflora (KP) extract on the physical fitness and heart rate variability (HRV) parameters in adolescent sport school students. 194 male students were recruited and randomized into two groups (n = 97), matched by age and sports. The KP-treated group received KP extract capsules at a dose of 360 mg/day and the control group received placebo capsules, continuously for 12 weeks. Physical fitness performance and HRV parameters were monitored with blood biochemical analysis for product safety. KP extract significantly increased the right-hand grip strength, the back-leg strength and maximal oxygen consumption (VO₂ max) and decreased the time used for 50-meter sprint test without changing the sit-and-reach test and the 40 yard technical test. For HRV parameters, KP extract significantly increased standard deviation of normal to normal intervals (SDNN), square root of the mean of square of successive normal to normal interval differences (RMSSD) and high frequency (HF) norm, without changing low frequency (LF) norm and LF/HF ratio. The increase in stress resistance and decrease in stress index were found in the KP-treated group, without changing the autonomic nervous system (ANS) activity and balance. Blood biochemical analysis showed normal values of all participants. This data indicates the safety and positive effects of KP on muscle strength, endurance and speed, but not on the flexibility and agility. The modulatory effects of KP extract on HRV parameters suggest its anti-stress effects and would encourage the application in a sport training and exercise.

Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The subcortical areas such as medial preoptic area (MPO), dorsomedial nucleus of the hypothalamus (DMH), basolateral (BLA) and central nuclei of the amygdala (CeA), and the cortical areas such as insular (IC) and anterior cingulate cortices (ACC) play an important role in pain control via the descending pain modulatory system. In the present study we examined the expression of phosphorylated -cAMP-response element binding protein (pCREB) and the acetylation of histone H3 in these subcortical and cortical areas after repeated restraint stress to reveal changes in the subcortical and cortical areas that affect the function of descending pain modulatory system in the rats with SIH. The repeated restraint stress for 3 weeks induced a decrease in mechanical threshold in the rat hindpaw, an increase in the expression of pCREB in the MPO and an increase in the acetylation of histone H3 in the MPO, BLA and IC. The MPO was the only area that showed an increase in both the expression of pCREB and the acetylation of histone H3 among these examined areas after the repeated restraint stress. Furthermore, the number of pCREB-IR or acetylated histone H3-IR cells in the MPO was negatively correlated with the mechanical threshold. Together, our data represent the importance of the MPO among the subcortical and cortical areas that control descending pain modulatory system under the condition of SIH.

Background: High-intensity interval training (HIIT) is superior to moderate-intensity continuous training in improving cardiorespiratory fitness in patients with cardiovascular disease, but is it safe, feasible and effective in patients with stroke? We investigated feasibility and effect of early, home-based HIIT in patients with lacunar stroke combined with usual care vs. usual care, only. Methods: Patients with minor stroke (severity: 55/58 point on the Scandinavian Stroke Scale) were randomized to HIIT or usual care in a randomized, controlled trial. We measured the following outcomes at baseline and post-intervention: cardiorespiratory fitness monitored as power output from the Graded Cycling Test with Talk Test (GCT-TT; primary outcome), physical activity, fatigue, depression, well-being, stress, cognition, endothelial function, blood pressure, body mass index, and biomarkers. Results: We included 71 patients (mean age 63.7 ± 9.2), 49 men, 31 in intervention group. Home-based HIIT was feasible with no reported adverse events in relation to the intervention. No significant change between the groups in GCT-TT power output was detected (p = 0.90). The change in time spent on vigorous-intensity activity was 2 h/week and 0.6 h/week, intervention and usual care, respectively (p = 0.045). There were no significant differences between groups in the remaining secondary outcomes. Conclusion: HIIT was feasible and safe in patients with lacunar stroke. Patients can engage early in home-based HIIT when involved in choosing exercise modality and guided by weekly motivational phone calls. Within 3 months, HIIT did, however, not yield effect on cardiorespiratory fitness. We await further evaluation of long-term effects of this intervention on continued regular physical exercise and cardiovascular event. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT02731235.

To investigate whether pressure pain threshold (PPT), determined by pressure algometry, can be used as an objective measure of perceived stress and job strain.

We used cross-sectional base line data collected during 1994 to 1995 within the Project on Research and Intervention in Monotonous work (PRIM), which included 3123 employees from a variety of Danish companies. Questionnaire data included 18 items on stress symptoms, 23 items from the Karasek scale on job strain, and information on discomfort in specified anatomical regions was also collected. Clinical examinations included pressure pain algometry measurements of PPT on the trapezius and supraspinatus muscles and the tibia. Associations of stress symptoms and job strain with PPT of each site was analyzed for men and women separately with adjustment for age body mass index, and discomfort in the anatomical region closest to the point of pressure algometry using multivariable linear regression.

We found significant inverse associations between perceived stress and PPT in both genders in models adjusting for age and body mass index: the higher level of perceived stress, the lower the threshold. For job strain, associations were weaker and only present in men. In men all associations were attenuated when adjusting for reported discomfort in regions close to the site of pressure algometry. The distributions of PPT among stressed and non-stressed persons were strongly overlapping.

Despite significant associations between perceived stress and PPT, the discriminative capability of PPT to distinguish individuals with and without stress is low. PPT measured by pressure algometry seems not applicable as a diagnostic tool of a state of mental stress.

Low pressure Pain Threshold (PPT) is considered a risk factor for Temporomandibular Disorders (TMD) and is influenced by psychological variables. Objectives To correlate deep pain sensitivity of masticatory muscles with prosthetic factors and Oral-Health-Related Quality of Life (OHRQoL) in completely edentulous subjects. Material and Methods A total of 29 complete denture wearers were recruited. The variables were: a) Pressure Pain Threshold (PPT) of the masseter and temporalis; b) retention, stability, and tooth wear of dentures; c) Vertical Dimension of Occlusion (VDO); d) Oral Health Impact Profile (OHIP) adapted to orofacial pain. The Kolmogorov-Smirnov test, the Pearson Product-Moment correlation coefficient, the Spearman Rank correlation coefficient, the Point-Biserial correlation coefficient, and the Bonferroni correction (α=1%) were applied to the data. Results The mean age (standard deviation) of the participants was of 70.1 years (9.5) and 82% of them were females. There were no significant correlations with prosthetic factors, but significant negative correlations were found between the OHIP and the PPT of the anterior temporalis (r=-0.50, 95% CI-0.73 to 0.17, p=0.005). Discussion The deep pain sensitivity of masticatory muscles in complete dentures wearers is associated with OHRQoL, but not with prosthetic factors.

We tested the hypothesis that pressure sensitivity of the sternum (PPS) is associated with autonomic nervous system (ANS) function as assessed by tilt table test (TTT). in patients with stable ischemic heart disease.

(1) To evaluate an association between PPS and systolic blood pressure (SBP) and heart rate (HR) responses to TTT; and (2) to test the hypothesis that a reduction of resting PPS raises the PPS, SBP and HR responses to TTT response and lowers risk factors for ANS dysfunction (ANSD).

Cross-sectional study: In 361 patients with stable ischemic heart disease we measured PPS, SBP, and HR during TTT. Intervention study: We reassessed subjects with persistent stress who concluded a stress intervention trial by a second TTT.

Cross-sectional study: Resting PPS and the PPS response to TTT were correlated (r = - 0.37). The PPS response to TTT was correlated with that of SBP (r = 0.44) and HR (r = 0.49), and with the number of risk factors for ANSD (r = - 0.21) (all p < 0.0001). Intervention study: A reduction in resting PPS was associated with an increment in PPS response to TTT (r = - 0.52, p < 0.0001). The greater this increment, the greater was the reduction in ANSD risk factors (r = - 0.23; p = 0.003).

The results are consistent with the hypothesis that PPS at rest and in response to TTT reflects ANS function.

Depressive symptoms and reduced quality of life (QOL) are parts of the chronic stress syndrome and predictive of adverse outcome in patients with ischemic heart disease (IHD). Chronic stress is associated with increased sensitivity for pain, which can be measured by algometry as Pressure Pain Sensitivity (PPS) on the sternum.

To evaluate if stress focus by self-measurement of PPS, followed by stress reducing actions including acupressure, can decrease depressive symptoms and increase psychological well-being in people with stable IHD.

Observer blinded randomized clinical trial over 3 months of either intervention or treatment as usual (TAU).

Intention to treat.

Two hundred and thirteen participants with IHD were included: 106 to active treatment and 107 to TAU. Drop-out: 20 and 12, respectively. The active intervention included self-measurement of PPS twice daily followed by acupressure as mandatory action, aiming at a reduction in PPS. Primary endpoint: change in depressive symptoms as measured by Major depression inventory (MDI). Other endpoints: changes in PPS, Well-being (WHO-5) and mental and physical QOL (SF-36).

At 3 months PPS decreased 28%, to 58, in active and 11%, to 72, in TAU, p<0.001. MDI decreased 22%, to 6.5, in active group vs. 12%, to 8.3 in TAU, p = 0.040. WHO-5 increased to 71.0 and 64.8, active group and TAU, p = 0.015. SF-36 mental score sum increased to 55.3 and 53.3, active and TAU, p = 0.08.

PPS measurements followed by acupressure reduce PPS, depressive symptoms and increase QOL in patients with stable IHD.

ClinicalTrials.gov NCT01513824.

To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC).

(1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group Intervention (PGI, n = 91) and no treatment (n = 86) with respect to a European Organization for Research and Treatment of Cancer (EORTC) questionnaire measured QOL.

(1) Resting PPS and changes in PPS during the intervention period correlated significantly to EORTC and Short Form 36 (SF 36) main scores: (all p < 0.05). Between BC, HSG and LSG there was a significant and positive correlation with respect to PPS, SF 36 main scores, depression, and clinical stress scores (all p < 0.05). However, the BC group scored significantly lower than both HSG and LSG (both p < 0.05) with respect to self-evaluated stress. (2) The PPS-guided intervention group improved EORTC main score, pain and nausea, when compared to the control groups (all p < 0.05).

PPS was positively associated with QOL, which was in contrast to self-evaluated stress. PPS-guided intervention improved QOL in women with breast cancer.

To evaluate the possible association between pressure pain sensitivity of the chest bone (PPS) and cardiovascular physiological factors related to persistent stress in connection with a three-month PPS-guided stress-reducing experimental intervention programme.

Forty-two office workers with an elevated PPS (≥ 60 arbitrary units) as a sign of increased level of persistent stress, completed a single-blinded cluster randomized controlled trial. The active treatment was a PPS (self-measurement)-guided stress management programme. Primary endpoints: Blood pressure (BP), heart rate (HR) and work of the heart measured as Pressure-Rate-Product (PRP); Secondary endpoints: Other features of the metabolic syndrome.

PPS decreased and changes in PPS after the intervention period were significantly associated with HR, PRP, body mass index (BMI) and visceral fat index (all correlation coefficients > 0.2, p < 0.05). Compared to the control cluster group, the active cluster group obtained a significant reduction in PPS, Low-density lipoprotein (LDL) cholesterol and total number of elevated risk factors (p < 0.05). On an individual level, significant and clinically relevant between-group reductions were observed in respect to BP, HR, PRP, total and LDL cholesterol, and total number of elevated risk factors (p < 0.05).

The stress intervention method applied in this study induced a decrease in PPS which was associated with a clinically relevant decrease in resting blood pressure, heart rate, work of the heart and serum cholesterols.

Chronic stress is prevalent in patients with ischemic heart disease (IHD) and worsens the long-term prognosis. Chronic stress is vaguely defined, but is associated with depressive symptoms, reduced psychological wellbeing, and reduced quality of life (QOL). Stress seems to induce hyperalgesia.The aim of the present study was to evaluate hyperalgesia by pressure pain sensitivity (PPS) in patients with IHD, and compare PPS to questionnaires measuring depressive symptoms, reduced psychological wellbeing, and QOL as markers of stress. Design. A cross-sectional study of 361 subjects with IHD.

PPS was measured on the sternum, and compared to the questionnaires: Clinical stress symptoms score (CSS), Major Depression Inventory (MDI), WHO-5 Wellbeing Index, and SF-36 QOL score.

PPS correlated to CSS (r = 0.20, p < 0.001), MDI (r = 0.14, p = 0.02), SF-36 mental component summary score (MCS) (r = - 0.10, p = 0.049), SF-36 physical component summary score (PCS) (r = - 0.17, p = 0.001), and self-perceived stress level (r = 0.15, p = 0.006). CSS correlated similarly (r = 0.5-0.7, all p < 0.001). Comparing subjects within the lowest vs. highest tertiles of PPS and CSS, the mean MDI score was 4 vs. 15, WHO-5 was 77 vs. 53, SF-36 PCS was 53 vs. 43, and SF-36 MCS was 58 vs. 46; all p < 0.001.

PPS reflected to a modest degree markers of chronic stress in IHD. PPS and CSS together might be useful as easy-to use tools for evaluating these markers in IHD patients.