Impact of homeostatic body hydration status, evaluated by hemodynamic measures, on different pain sensitization paths to a chronic pain syndrome.

Contrasting findings on the mechanisms of chronic pain and hypertension development render the current conventional evidence of a negative relationship between blood pressure (BP) and pain severity insufficient for developing personalized treatments. In this interdisciplinary study, patients with fibromyalgia (FM) exhibiting clinically normal or elevated BP, alongside healthy participants were assessed. Different pain sensitization responses were evaluated using a dynamic 'slowly repeated evoked pain' (SREP) measure, as well as static pain pressure threshold and tolerance measures. Cardiovascular responses to clino-orthostatic (lying-standing) challenges were also examined as acute re- and de-hydration events, challenging cardiovascular and cerebrovascular homeostasis. These challenges involve compensating effects from various cardiac preload or afterload mechanisms associated with different homeostatic body hydration statuses. Additionally, hair cortisol concentration was considered as a factor with an impact on chronic hydration statuses. Pain windup (SREP) and lower pain threshold in FM patients were found to be related to BP rise during clinostatic (lying) rehydration or orthostatic (standing) dehydration events, respectively. These events were determined by acute systemic vasoconstriction (i.e., cardiac afterload response) overcompensating for clinostatic or orthostatic cardiac preload under-responses (low cardiac output or stroke volume). Lower pain tolerance was associated with tonic blood pressure reduction, determined by permanent hypovolemia (low stroke volume) decompensated by permanent systemic vasodilation. In conclusion, the body hydration status profiles assessed by (re)activity of systemic vascular resistance and effective blood volume-related measures can help predict the risk and intensity of different pain sensitization components in chronic pain syndrome, facilitating a more personalized management approach.

Blunted short-term autonomic cardiovascular reactivity to orthostatic and clinostatic challenges in fibromyalgia as an indicator of the severity of chronic pain.

Fibromyalgia is a long-term pain disorder that has been related to autonomic dysfunctions and reduced cardiovascular reactivity. We aimed to assess the dynamic short-term cardiovascular responses to postural changes in fibromyalgia. Thirty-eight women with fibromyalgia and thirty-six healthy women underwent the "Chronic Pain Autonomic Stress Test". Electrocardiogram, blood pressure and impedance cardiography were continuously recorded during active standing and lying down. Second-by-second values were derived over the first 30 s of each posture. Lower reactivity during the beginning of each position was observed in fibromyalgia sufferers compared to healthy women, with smaller responses seen during stand up in heart rate, blood pressure, cardiac output, total peripheral resistance, and pre-ejection period, and smaller changes during lying down in heart rate, cardiac output and total peripheral resistance. The magnitude of the autonomic adjustments to postural changes was inversely associated with the severity of clinical pain. These findings indicate an early impaired autonomic cardiovascular response to orthostatic and clinostatic challenges in fibromyalgia, suggesting less autonomic flexibility and adaptability to situational demands and challenges. Short-term second-by-second cardiovascular measures may be useful in the clinical assessment of fibromyalgia.

Personalized behavior management as a replacement for medications for pain control and mood regulation.

A lack of personalized approaches in non-medication pain management has prevented these alternative forms of treatment from achieving the desired efficacy. One hundred and ten female patients with fibromyalgia syndrome (FMS) and 60 healthy women without chronic pain were assessed for severity of chronic or retrospective occasional pain, respectively, along with alexithymia, depression, anxiety, coping strategies, and personality traits. All analyses were conducted following a 'resource matching' hypothesis predicting that to be effective, a behavioral coping mechanism diverting or producing cognitive resources should correspond to particular mechanisms regulating pain severity in the patient. Moderated mediation analysis found that extraverts could effectively cope with chronic pain and avoid the use of medications for pain and mood management by lowering depressive symptoms through the use of distraction mechanism as a habitual ('out-of-touch-with-reality') behavior. However, introverts could effectively cope with chronic pain and avoid the use of medications by lowering catastrophizing through the use of distraction mechanism as a situational ('in-touch-with-reality') behavior. Thus, personalized behavior management techniques applied according to a mechanism of capturing or diverting the main individual 'resource' of the pain experience from its 'feeding' to supporting another activity may increase efficacy in the reduction of pain severity along with decreasing the need for pain relief and mood-stabilizing medications.

Making the choice between bioelectrical impedance measures for body hydration status assessment.

Situational or persistent body fluid deficit (i.e., de- or hypo-hydration) is considered a significant health risk factor. Bioimpedance analysis (BIA) has been suggested as an alternative to less reliable subjective and biochemical indicators of hydration status. The present study aimed to compare various BIA models in the prediction of direct measures of body compartments associated with hydration/osmolality. Fish (n = 20) was selected as a biological model for physicochemically measuring proximate body compartments associated with hydration such as water, dissolved proteins, and non-osseous minerals as the references or criterion points. Whole-body and segmental/local impedance measures were used to investigate a pool of BIA models, which were compared by Akaike Information Criterion in their ability to accurately predict the body components. Statistical models showed that 'volumetric-based' BIA measures obtained in parallel, such as distance2/Rp, could be the best approach in predicting percent of body moisture, proteins, and minerals in the whole-body schema. However, serially-obtained BIA measures, such as the ratio of the reactance to resistance and the resistance adjusted for distance between electrodes, were the best fitting in predicting the compartments in the segmental schema. Validity of these results should be confirmed on humans before implementation in practice.

Hypolithic communities shape soils and organic matter reservoirs in the ice-free landscapes of East Antarctica.

The soils of East Antarctica have no rhizosphere with the bulk of organo-mineral interactions confined to the thin microbial and cryptogamic crusts that occur in open or cryptic niches and are collectively known as biological soil crust (BSC). Here we demonstrate that cryptic hypolithic varieties of BSC in the Larsemann Hills of East Antarctica contribute to the buildup of soil organic matter and produce several types of continuous organogenous horizons within the topsoil with documented clusters of at least 100 m2. Such hypolithic horizons accumulate 0.06-4.69% of organic carbon (TOC) with isotopic signatures (δ13Corg) within the range of -30.2 - -24.0‰, and contain from 0 to 0.38% total nitrogen (TN). The properties of hypolithic organic matter alternate between cyanobacteria- and moss-dominated horizons, which are linked to the meso- and microtopography patterns and moisture gradients. The major part of TOC that is stored in hypolithic horizons has modern or centenary 14C age, while the minor part is stabilized on a millennial timescale through shallow burial and association with minerals. Our findings suggest that hypolithic communities create a "gateway" for organic carbon to enter depauperate soils of the Larsemann Hills and contribute to the carbon reservoir of the topsoil at a landscape level.

Impact of antihypertensive treatment on resiliency to clinical pain.

OBJECTIVES: Although progress has been made in the regulation of hypertension over the past decades, the USA and some other countries have faced a significant rise in incidence of chronic pain management cases during the same period. Studies of the relationship between pain and blood pressure (BP) regulations propose that these two processes may be interconnected. Studies of effects of antihypertensive treatment on pain in general and its chronification have never been reviewed. METHODS: A narrative review of respective studies with analysis of credibility of the findings was conducted. RESULTS: Some studies have suggested that aggressive reduction of high BP may contribute to a return in pain symptoms and may require more aggressive, long-term pain management. Other studies propose that long-term antihypertensive medication could also increase the risk for new cases of chronic pain. Pain initiates a central neuroplastic resetting of the baroreceptor activation accounting for sustained increase of BP with an adaptive 'pain-killing' or maladaptive 'pain-complication' effect associated with pain chronification, and these mechanisms may be moderated by antihypertensive medications. However, different antihypertensive drugs and nondrug treatments may diversely affect pain mechanisms at different stages of treatments. CONCLUSION: Uncontrollable reduction of high BP in some patients with hypertension could increase the risk for chronic pain incidence and its severity. Practical recommendations in BP control should be reconsidered to take into account patients' chronic pain. Further research is needed of moderation effects of different antihypertensive manipulations on pain to improve pain management in these patients.

Cardiovascular phenotyping for personalized lifestyle treatments of chronic abdominal pain in Irritable Bowel Syndrome: A randomized pilot study.

BACKGROUND: Different physical exercise interventions for pain and other related symptoms largely follow non-personalized guidelines and show a high degree of variability in outcome. These interventions are considered to have different pathways toward improvement in autonomic regulation of energy metabolism. The current pilot study was conducted to assess the predictive value of individual cardiovascular (CV) activity markers at rest to predict clinical outcomes for two popular exercise-based interventions (walking and yoga) in patients with Irritable Bowel Syndrome (IBS). METHODS: Twenty-seven adult participants with IBS were randomly assigned to a 16-biweekly Iyengar yoga or walking program. They completed pre- and post-treatment assessments on IBS symptom severity, affective and somatic complaints, and various measures of resting autonomic function including blood pressure (BP), heart rate and its variability, baroreceptor sensitivity (BRS) to activations and inhibitions with gains of brady- and tachycardiac baro-responses, and BP start points for these spontaneous baroreflexes. RESULTS: Pretreatment BRS was differentially related to clinical response for the treatment groups. Specifically, a significant decrease in pain severity was found in response to yoga for those participants who had lower resting BRS to activations, but decreased pain severity was associated with higher resting BRS for those in the walking group. The effect was not related to affective symptom relief. Other CV measures showed similar associations with clinical outcomes for both groups. CONCLUSIONS: The data suggest therefore that CV based phenotypes may be useful in personalizing clinical interventions for IBS. They may also point to autonomic mechanisms that are targets for such interventions.

Placental Chorangiosis: Increased Risk for Cesarean Section.

We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT) and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR), and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of "chorangiosis" on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

Orthostatic cardiovascular profile of subjective well-being.

Previous clinical and elderly population studies have found that affective well-being can be assessed by clino-orthostatic cardiovascular reactivity. This study explored this relationship in a young healthy sample, and with respect to cognitive appraisals of well-being. Four successive readings of blood pressure (BP) and heart rate (HR) after lying down (clinostatic probe) followed by four successive readings after standing up (orthostatic probe) were obtained from 52 healthy students along with questionnaire-reported well-being. Analyses indicated that a deeper drop of systolic BP (SBP) and mean arterial (MAP) pressure during supine was related to higher positive mood, but higher and more stable orthostatic MAP and HR response were related to lower negative mood. A higher diastolic BP while standing upright and lower SBP in general were associated with higher optimism and higher global life satisfaction, respectively. The findings confirm previous results and indicate that cognitive appraisals of well-being are also related to BP regulation.

Central and peripheral pathogenetic forms of type 2 diabetes: a proof-of-concept study.

HYPOTHESIS: Previous studies provide evidence that glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) should not be considered as interchangeable alternatives in the diagnosis of the same type 2 diabetes, but as indicators of its different pathogenetic subtypes. This study was conducted to determine whether a particularly high amount of glucose in either HbA1c form or in fasting plasma would be found in diabetic patients genetically predisposed for either intensive cognitive or intensive muscle metabolic activity, respectively. METHODS: HbA1c and FPG levels, polymorphisms of genes indicating the predisposition to different cognitive activity (the dopamine D2 receptor (DRD2/ANKK1)), muscle activity (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A(PPARGC1A))), and vascular regulation of general metabolic activity (the angiotensin 1 converting enzyme (ACE)) were assessed in diabetic patients and nondiabetic controls. RESULTS: DRD2/ANKK1 polymorphism that affects baseline central arousal determined HbA1c variations uncorrelated with FPG in total and clinical groups. The mutation of PGC1A mainly affecting peripheral glucose metabolism had an effect on FPG correlated or uncorrelated with HbA1c depending on the effect assessment in the total sample or in the nondiabetic group, respectively. ACE insertion/deletion (I/D) gene polymorphism was associated with both HbA1c and FPG fluctuations, but only in diabetic patients. CONCLUSION: The findings provide evidence that the HbA1c and FPG may predict the risks for different subtypes of type 2 diabetes associated with either brain or muscle metabolic activity in genetically vulnerable people.

Baroreflex mechanisms in Irritable Bowel Syndrome: Part I. Traditional indices.

OBJECTIVE: This study was conducted to present evidence of differences in autonomic regulation of cardiovascular activity and its role in the severity of specific (disease-related) and non-specific (negative affect and chronic pain-related) symptoms in individuals with Irritable Bowel Syndrome (IBS). METHODS: Seventy-eight female patients with IBS and 27 healthy women age 18-62 years were assessed for IBS symptoms, negative affect, and baroreceptor sensitivity (BRS), blood pressure (BP), heart rate, and heart rate variability (HRV) at rest. Direct and indirect regression effects were examined with application of the bootstrap procedure to validate findings. RESULTS: IBS was reliably related to lower resting BRS, higher BP, and higher negative affect compared to healthy controls. Longer disease duration (chronicity) was related to BRS decrease coupled with systolic BP increase (95% CIs=-0.14 to -0.01). Three autonomic mechanisms associated with BRS decrease were found to further regulate severity of IBS symptoms. Lower BRS was related to higher IBS severity in general if the effect was transferred through the decrease of low frequency power of HRV (e.g., 95% CIs=-0.039 to -0.001 for abdominal pain severity). However, lower BRS was related to lower IBS severity in general if the effect was transferred through diastolic BP increase (95% CIs=0.01-0.11 for abdominal pain severity). Lower BRS was related to higher abdominal pain severity coupled with high negative affect if the effect was transferred through the decrease of higher frequency power of HRV (95% CIs=-0.026 to -0.003). CONCLUSIONS: These findings indicate that different cardiovascular mechanisms are associated with IBS development and the increase and decrease of severity of IBS symptoms. Their assessment suggests ways to personalize treatment of IBS.

Cardiovascular activity and chronic pain severity.

OBJECTIVE: Objective markers of chronic pain severity are needed when examining and treating patients with chronic pain whose suffering may be overstated or underestimated. This study tested a hypothesis that the strength of cardiovascular (CV) reactivity in response to a social evaluative threat and orthostatic challenge is a reliable index of severity of pain-related complaints. METHODS: Measurement of CV reactivity and response styles in 34 men and 16 women with chronic pain from different bodily injuries, were retrieved from a larger database of patients. Measurement of CV reactivity in response to a postural challenge was repeated twice (sessions 1 and 2) on the same day of a medical examination which includes a psychosocial evaluation . RESULTS: A decrease in systolic blood pressure (SBP) from session 1 to session 2 was found in subjects with low pain severity scores, but not in those with high pain severity scores. High scores for pain catastrophizing/ magnification and pain-related emotional distress were independently associated respectively with a SBP increase at an early-point in time and a SBP decrease at a mid-point in time after standing up from lying down. Stronger heart rate reactivity responses to orthostatic challenge indicated greater protection against the presence of these chronic pain symptoms. CONCLUSIONS: This biobehavioral protocol enables measurement of chronic pain suffering and protection in three dimensions: physical, emotional, and cognitive.

Resilience to orthostasis and haemorrhage: A pilot study of common genetic and conditioning mechanisms.

A major challenge presently is not only to identify the genetic polymorphisms increasing risk to diseases, but to also find out factors and mechanisms, which can counteract a risk genotype by developing a resilient phenotype. The objective of this study was to examine acquired and innate vagal mechanisms that protect against physical challenges and haemorrhages in 19 athletes and 61 non-athletes. These include examining change in heart rate variability (HF-HRV; an indicator of vagus activity) in response to orthostatic challenge, platelet count (PLT), mean platelet volume (MPV), and single-nucleotide polymorphisms in genes that encode several coagulation factors, PAI-1, and MTHFR. Individual differences in PLT and MPV were significant predictors, with opposite effects, of the profiles of the HF-HRV changes in response to orthostasis. Regular physical training of athletes indirectly (through MPV) modifies the genetic predisposing effects of some haemostatic factors (PAI-1 and MTHFR) on vagal tone and reactivity. Individual differences in vagal tone were also associated with relationships between Factor 12 C46T and Factor 11 C22771T genes polymorphisms. This study showed that genetic predispositions for coagulation are modifiable. Its potential significance is promoting advanced protection against haemorrhages in a variety of traumas and injuries, especially in individuals with coagulation deficits.

Heart rate variability and treatment outcome in major depression: a pilot study.

Variations in heart rate variability (HRV) have been associated with major depressive disorder (MDD), but the relationship of baseline HRV to treatment outcome in MDD is unclear. We conducted a pilot study to examine associations between resting baseline HRV and MDD treatment outcome. We retrospectively tested several parameters of HRV in an MDD treatment study with escitalopram (ESC, N=26) to generate a model of how baseline HRV related to treatment outcome, and cross-validated the model in a separate trial of MDD treatment with Iyengar yoga (IY, N=16). Lower relative power of very low frequency (rVLF) HRV at baseline predicted improvement in depressive symptoms when adjusted for age and gender (R2>.43 and p<0.05 for both trials). Although vagal parasympathetic measures were correlated with antidepressant treatment outcome, their predictive power was not significant after adjusting for age and gender. In conclusion, baseline resting rVLF was associated with depression treatment outcome in two independent MDD treatment studies. These results should be interpreted with caution due to limited sample size, but a strength of this study is its validation of the rVLF predictor in an independent sample. rVLF merits prospective confirmation as a candidate biomarker.

An externally oriented style of thinking as a moderator of responses to affective films in women.

This study was conducted to test the hypothesis that differences in alexithymia would moderate coupling in physiological and subjective-experiential responses to two affective films, which were shown to induce a common negative (sad) feeling, but to provoke different hyper- or hypo-arousal physiological responses (e.g., heart rate acceleration or deceleration) associated with antipathic or empathic context, respectively (Davydov et al., 2011). Only women were studied as persons showing more reactivity to sad films than men. Reactivity was evaluated for facial behavior, physiological arousal, and subjective experience. Some other affective and cognitive disposition factors (e.g., depression and defensiveness) were considered for evaluating their probable mediation of the alexithymia's effects. While subjective experience was not affected by alexithymia, high scorers on the externally-oriented thinking factor showed reduced physiological reactivity in both film conditions. These effects were mediated through different disposition factors: either low affectivity (low depressed mood), which mediated alexithymia's effect on hyper-arousal responses (e.g., decrease of heart rate acceleration), or impression management (other-deception), which mediated alexithymia's effect on hypo-arousal responses (e.g., decrease of heart rate deceleration).

Alexithymia is associated with an augmenter profile, but not only: evidence for anticipation to arousing music.

It has been suggested that high alexithymia scorers have an 'augmenter' profile which amplifies their physiological and subjective responses to highly arousing stimuli. The aim of this study was to test this theory using several physiological measures. Participants listened to musical excerpts either in a 'weak-to-strong' or a 'strong-to-weak' order of arousing levels of stimuli. The results show that alexithymia was associated with an augmenter profile for subjective reports for the most arousing stimulus and with stronger skin conductance level responses in the 'strong-to-weak' order. These results partially support the augmenter profile and reveal that alexithymia may be associated with higher anticipation for the most arousing excerpt.