Confusion and controversy in the stress field.

An attempt is made to further clarify present areas of controversy in the stress field, in response to a two-part article by Dr. John W. Mason which concludes in this issue of the Journal of Human Stress. The author tries to elucidate each source of confusion enumerated by Dr. Mason. The continued use of the word "stress" for the nonspecific response to any demand is deemed most desirable. The once vague term can now be applied in a well-defined sense and is accepted in all foreign languages as well, including those in which no such word existed previously in any sense. Subdivision of the stress concept has become necessary as more recent work has led to such notions as "eustress," "distress," "systemic stress" and "local stress." Confusion between stress as both an agent and a result can be avoided only by the distinction between "stress" and "stressor". It is explained that the stress syndrome is--by definition--nonspecific in its causation. However, depending upon conditioning factors, which can selectively influence the reactivity of certain organs, the same stressor can elicit different manifestations in different individuals.     

Concepts in plant stress physiology. Application to plant tissue cultures

Because the term stress is used, most often subjectively, with variousmeanings, this paper first attempts to clarify the physiological definition,andthe appropriate terms as responses in different situations. The flexibility ofnormal metabolism allows the development of responses to environmental changeswhich fluctuate regularly and predictably over daily and seasonal cycles. Thusevery deviation of a factor from its optimum does not necessarily result instress. Stress begins with a constraint or with highly unpredictablefluctuations imposed on regular metabolic patterns that cause bodily injury,disease, or aberrant physiology. Stress is the altered physiological conditioncaused by factors that tend to alter an equilibrium. Strain is any physicaland/or chemical change produced by a stress, i.e. every established condition,which forces a system away from its thermodynamic optimal state. The papersecondly summarises the Strasser's state-change concept which is preciselythat suboptimality is the driving force for acclimation (genotype level) oradaptation (population level) to stress. The paper continues with the actualknowledge on the mechanisms of stress recognition and cell signalling. Briefly:plasma membranes are the sensors of environmental changes; phytohormones andsecond messengers are the transducers of information from membranes tometabolism; carbon balance is the master integrator of plant response; betwixtand between, some genes are expressed more strongly, whereas others arerepressed. Reactive oxygen species play key roles in up- and down-regulation ofmetabolism and structure. The paper shows finally that the above concepts canbeapplied to plant tissue cultures where the accumulating physiological andgenetical deviations (from a normal plant behaviour) are related to thestressing conditions of the in vitro culture media and ofthe confined environment. The hyperhydrated state of shoots and the cancerousstate of cells, both induced under conditions of stress in invitro cultures, are identified and detailed, because they perfectlyillustrate the stress-induced state-change concept. It is concluded that stressresponses include either pathologies or adaptive advantages. Stress may thuscontain both destructive and constructive elements : it is a selection factoraswell as a driving force for improved resistance and adaptive evolution.     

Individual behavioral and autonomic response to emotional stress in humans

Healthy subjects (n = 53) performed a sound version of the proof-reading test under normal conditions and in the state of emotional stress. Stress resistance was evaluated by the overall number of errors. The propensity to active or passive response to stress was evaluated by the number of "false alarms" and signal omissions. The reaction pattern to emotional stress in stress-resistant subjects, irrespective of their behavioral features, consisted in an increase in sympathetic effects on the cardiac rhythm and a decrease in the reaction time to significant signals. In subjects with low stress resistance, no statistically significant changes in the level of sympathetic tone and reaction time were revealed in the state of stress. Subjects with active behavioral response to stress, irrespective of their level of stress resistance, were characterized by aggressiveness, boldness and independence. Subjects with passive response to stress were inclined to conformism, dependence, and passivity.     

The ‘stress’ concept in microalgal biology—homeostasis,acclimation and adaptation

The term ‘stress’ is widely used in the algal literature, usually in the context of the response of algae to changed abiotic and biotic factors. ‘Stress’ is seen as the cause of changes in algal metabolism and composition and often as a factor inducing the overproduction of particular desirable secondary metabolites. However, ‘stress’ is used differently by different authors and is often ill-defined, with no clear separation of cause and effect. This lack of a defined stress concept leads to poor experimental design, miscommunication of results and potentially erroneous conclusions. This paper reviews the stress concept as it applies to algae, especially microalgae. Here, stress is defined as the disruption of homeostasis due to a stressor and the stress response represents the changes in cell metabolism during acclimation and the restoration of homeostasis. Once homeostasis is restored the cell is no longer stressed. The stages of the stress response, i.e. alarm, regulation, acclimation and adaptation, are described. The well-studied responses of the green halophilic alga Dunaliella to changes in salinity are used as an example to illustrate the stress response and acclimation to the changed salinity.     

A short note on oxytocin and stress attenuation

Stress is integral part of life and it initiates appropriate response at times of adversities to promise survival. Stress could be either physiological or psychogenic. Stress is often psychogenic in nature and it induces the release of cortisol from adrenal cortex into circulation by activating Hypo thalamo-pituitary-adrenal axis (HPA). Cortisol thus released mediates the stress response by its catabolic effects to enhance the activity of vital organs during emergency. However, prolonged activation of the HPA axis can lead to physical and mental illness as an outcome of persistent stress. Nature has bestowed the biological system with an array of endogenous mechanisms to buffer stress. Oxytocin, a nano-peptide released by the magno-cellular neurons of hypothalamic paraventricular nucleus (PVN) is an efficient stress buffering neuro-peptide. This hormone mediates many physiological and behavioural functions get released during stress. It attenuates the stress axis initiated by the release of corticotropin releasing hormone (CRH) from the parvocellular neurons of the same hypothalamic nucleus. Oxytocin released by PVN exerts an inhibitory effect on the release of CRH by down-regulating the expression of the gene that transcribes for this hypothalamic hormone. Thus, it inhibits the release of adreno cotico trophic hormone (ACTH) and cortisol, exerting an overall suppressive modulation of the stress axis and attenuates stress.     

Stress of different types increases the proinflammatory load in rheumatoid arthritis

Stress in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) stimulates proinflammatory mechanisms due to the defect of stress response systems (for example, the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis). Among other mechanisms, the loss of sympathetic nerve fibers in inflamed tissue and inadequate cortisol secretion in relation to inflammation lead to an enhanced proinflammatory load in RA. Stress and the subsequent stimulation of inflammation (systemic and local) lead to increased sensitization of pain and further defects of stress response systems (vicious cycle of stress, pain, and inflammation).     

I. Stress and hepatic inflammation

Stress is an ever-present part of modern life. The "stress response" constitutes an organism's mechanism for coping with a given stress and is mediated via the release of glucocorticoids and catecholamines. Patients often complain of stress-related worsening of their liver disease; however, the interrelationship between stress and hepatic inflammation is incompletely understood and has received little scientific attention. Considering the broad impact glucocorticoids and catecholamines have on immune cell function, it is very likely that stress has a significant impact on the hepatic inflammatory response. This themes article discusses studies of the stress response and its peripheral effectors (glucocorticoids and catecholamines) in liver disease and their impact on hepatic inflammation and outlines potential areas for future scientific investigation.     

The stressed synovium

This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies.     

Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies.     

Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

Background

Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia.

Methods

Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test (“Trier Social Stress Test”).

Results

Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain.

Conclusions

Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.     

Psychophysiological responses to stress after stress management training in patients with rheumatoid arthritis

Background

Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA).

Methods

Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST) 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed.

Results

Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (α-amylase) or endocrine (cortisol) responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile.

Conclusion

A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness.

Trial Registration

TrialRegister.nl NTR1193     

How stress selects for reversible phenotypic plasticity

Stress occurring in periods shorter than life span strongly selects for reversible phenotypic plasticity, for maximum reliability of stress indicating cues and for minimal response delays. The selective advantage of genotypes that are able to produce adaptive reversible plastic phenotypes is calculated by using the concept of environmental tolerance. Analytic expressions are given for optimal values of mode and breadth of tolerance functions for stress induced and non-induced phenotypes depending on (1) length of stress periods, (2) response delay for switching into the induced phenotype, (3) response delay for rebuilding the non-induced phenotype, (4) intensity of stress, i.e. mean value of the stress inducing environment, (5) coefficient of variation of the stress environment and (6) completeness of information available to the stressed organism. Adaptively reversible phenotypic plastic traits will most probably affect fitness in a way that can be described by simultaneous reversible plasticity in mode and breadth of tolerance functions.     

Sexual dimorphism in reactions to stress during regular and altered photoperiods

Sexual dimorphism of rats in response to physiological stress influences was discovered. The emotional stress in female animals caused a sharp intensification of synthesis and corticosterone secretion, while in males there was an increase only in hormone synthesis and not its secretion. Females are more sensitive even to short-term changes in photoperiod. Stress reaction in females under conditions of three-day light depressed sharply and increased under conditions of three-day darkness. Stress reaction in males did not change under these conditions. The reactivity of adaptation system in females shortens the period of adaptation to the altered illumination regimen, which is manifested in the restoration of typical stress reactions. In males, refractoriness to weak stress influences lengthens the period of adaptation, which is manifested in the suppression of typical stress reaction observed in males.     

Molecular and structural antioxidant defenses against oxidative stress in animals

In this review, it is our aim 1) to describe the high diversity in molecular and structural antioxidant defenses against oxidative stress in animals, 2) to extend the traditional concept of antioxidant to other structural and functional factors affecting the "whole" organism, 3) to incorporate, when supportable by evidence, mechanisms into models of life-history trade-offs and maternal/epigenetic inheritance, 4) to highlight the importance of studying the biochemical integration of redox systems, and 5) to discuss the link between maximum life span and antioxidant defenses. The traditional concept of antioxidant defenses emphasizes the importance of the chemical nature of molecules with antioxidant properties. Research in the past 20 years shows that animals have also evolved a high diversity in structural defenses that should be incorporated in research on antioxidant responses to reactive species. Although there is a high diversity in antioxidant defenses, many of them are evolutionary conserved across animal taxa. In particular, enzymatic defenses and heat shock response mediated by proteins show a low degree of variation. Importantly, activation of an antioxidant response may be also energetically and nutrient demanding. So knowledge of antioxidant mechanisms could allow us to identify and to quantify any underlying costs, which can help explain life-history trade-offs. Moreover, the study of inheritance mechanisms of antioxidant mechanisms has clear potential to evaluate the contribution of epigenetic mechanisms to stress response phenotype variation.     

In situ multi-level analysis of viscoelastic deformation mechanisms in tendon collagen

Tendon is a hydrated multi-level fibre composite, in which time-dependent behaviour is well established. Studies indicate significant stress relaxation, considered important for optimising tissue stiffness. However, whilst this behaviour is well documented, the mechanisms associated with the response are largely unknown. This study investigates the sub-structural mechanisms occurring during stress relaxation at both the macro (fibre) and nano (fibril) levels of the tendon hierarchy. Stress relaxation followed a two-stage exponential behaviour, during which structural changes were visible at the fibre and fibril levels. Fibril relaxation and fibre sliding showed a double exponential response, while fibre sliding was clearly the largest contributor to relaxation. The amount of stress relaxation and sub-structural reorganisation increased with increasing load increments, but fibre sliding was consistently the largest contributor to stress relaxation. A simple model of tendon viscoelasticity at the fibril and fibre levels has been developed, capturing this behaviour by serially coupling a Voigt element (collagen fibril), with two Maxwell elements (non-collagenous matrix between fibrils and fibres). This multi-level analysis provides a first step towards understanding how sub-structural interactions contribute to viscoelastic behaviour. It indicates that nano- and micro-scale shearing are significant dissipative mechanisms, and the kinetics of relaxation follows a two-stage exponential decay, well fitted by serially coupled viscoelastic elements.     

9. Stress physiology of forest trees: The role of plant growth regulators

Abiotic and biotic stresses elicit changes in normal physiology of trees. Plant growth regulators (PGR) are involved in the stress response and appear to have two roles: 1) to minimize the impact of the stress on the tree and; 2) to trigger stress resistance mechanisms. In the latter case the PGR-induced changes appear to enhance resistance to subsequent stress. This cross-adaptation to stress is important in trees.The role of PGRs in the physiological response to the abiotic stresses of water deficit, water excess, temperature, nutrition and mechanical perturbation is discussed along with cross-adaptation in the interactions of these stresses. Disease response and defense, and plant-plant communications involve PGRs and are topics covered with respect to biotic stress. Stress leads to early senescence and abscission in trees. These processes are controlled by PGRs and are briefly discussed.