Sympathetic Muscle Tension and Stress

One of the well-known phenomena that accompany the stress response is the spontaneous and uncontrollable action of the sympathetic nervous system on the musculoskeletal structures of the body. Stress, muscular tension and pain often go hand in hand.

The Alarm or Stress Response of the Sympathetic Nervous System

bungee-jumpingWhen the sympathetic nervous system is suddenly stimulated by a stressor, there is an almost immediate increase in the body’s ability to carry out unusually vigorous muscle activity, even in individuals who would ordinarily not be capable of it.This almost prodigious increase in strength is facilitated by a cascade of physiological changes that is precipitated by stressful situations.

These changes, which take place in a matter of mere seconds, include:

  1. Increased arterial blood pressure.
  2. Increased blood flow to the muscles along with a corresponding decrease in blood supply to the gastrointestinal tract and the kidneys, which are not needed in mounting the body’s rapid response to the threat.
  3. Increased rates of cellular metabolism, which speed up the body’s rate of functioning.
  4. Increased blood glucose concentration, which provides increased levels of energy.
  5. Increased glycolysis in the liver and in the muscle, also a factor in energy supply.
  6. Increased muscle tension and preparedness to work, which increase tone and strength.
  7. Increased mental activity, which provides acuity, alertness and greater focus on the threat.
  8. Increased rate of blood coagulation, which protects the body from significant blood loss if it should sustain minor cuts and puncture.

The combined effects of the mobilization of virtually all principal organs is what enables the body to perform significantly more strenuous physical activity than it is ordinarily possible. Stress of any kind, physical, emotional or mental, excites the sympathetic system, whose purpose is to provide above-normal activation of the body’s resources. Because of this stimulation, the stress response is often referred to as the sympathetic stress response.

Emotional vs. Physical Stress

The sympathetic system is activated during physical danger, but it is also and more frequently activated by many real or perceived emotional stressors. Guyton-Hall cite the example of anger or rage,

…which is elicited to a great extent by stimulating the hypothalamus, signals are transmitted downward through the reticular formation of the brain stem and into the spinal cord to cause massive sympathetic discharge; most aforementioned sympathetic events ensue immediately. This is called the sympathetic alarm reaction. It is also called the fight or flight reaction because an animal in this state decides almost instantly whether to stand and fight or to run. In either event, the sympathetic alarm reaction makes the animal’s subsequent activities vigorous.
–Textbook of medical physiology by Arthur C. Guyton & John E. Hall, 11th ed.

Chronic Stress

The same exact response can be elicited even daily in individuals exposed to multiple or repeating stressors, such as a negative environment, a dysfunctional relationship, poor working conditions, or difficult socio-economic challenges. In this case, the muscle tension and sympathetic stimulation can be so great and so frequent that the body cannot return to a normal state of relaxation, in which case a chronic stress condition can ensue.

The Bipolar Hippocampus

aavanGogh_1888_PontLAngloisA Vanderbilt University study just published in the Archives of General Psychiatry reveals that hippocampal interneurons are modified by bipolar depression. The hippocampus is an important component of the limbic system that acts as the switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive. Because of its central function in the modulation of emotions, the hippocampus is believed to have a role in mood disorders such as depression. Numerous postmortem studies conducted on the brain of individuals who were affected by bipolar disorder have shown a decreased density and decreased gene expression of hippocampal interneurons. These findings, however, had not been confirmed by neuroimaging studies of hippocampal volume and function in live subjects—until now.

hippocampal_anatomyTo assess hippocampal volume, neuron number, and interneurons the Vanderbilt study examined sample brain specimens of hippocampi from 14 individuals with bipolar disorder and compared them to those taken from 18 healthy control subjects. The specimens, provided by the Harvard Brain Tissue Resource Center at McLean Hospital, were cut at 2.5-mm intervals and sections from each tissue slice were either Nissl-stained or stained with antibodies against somatostatin or parvalbumin. Messenger RNA was extracted from fixed tissue and real-time quantitative polymerase chain reaction was performed.

The researchers analyzed each sample by measuring the volume of pyramidal and nonpyramidal cell layers, overall neuron number and size, number of somatostatin- and parvalbumin-positive interneurons, and messenger RNA levels of somatostatin, parvalbumin, and glutamic acid decarboxylase 1.

After comparing healthy and unhealthy hippocampal samples, the study showed that the 2 groups did not differ in the total number of hippocampal neurons, but the bipolar disorder group showed reduced volume of the nonpyramidal cell layers, reduced somal volume in cornu ammonis sector 2/3, reduced number of somatostatin- and parvalbumin-positive neurons, and reduced messenger RNA levels for somatostatin, parvalbumin, and glutamic acid decarboxylase 1.

According to the researchers, these results indicate a specific alteration of hippocampal interneurons in bipolar disorder, which is likely to produce a hippocampal dysfunction that can have, among other manifestations, an effect on the onset and severity of bipolar depression.

Stress Hardware Review: The HPA

ScenicSkyway_EN-US2786891862In addition to genetic factors, there are many external factors that influence our individual vulnerability to stress, including childhood trauma, early environmental factors, major life events or physical illness. These factors can influence the intensity and duration of our stress reaction, in many cases producing long-lasting effects. The stress caused by traumatic events may cause chronic stress syndromes such as PTSD, promote the onset of physical disease or worsen existing conditions, including rheumatoid arthritis, chronic pain, fibromyalgia, and multiple sclerosis, among others.

However, while individuals vary greatly in their ability to respond adequately to stressful situations, every human body is programmed and equipped to respond to the initial stressor in the same biochemical way. Among the principal structures that are immediately mobilized in the event of a physical or psychological threat is the hypothalamic-pituitary-adrenal axis (HPA). The HPA consists of three elements connected by blood vessels: the hypothalamus, the pituitary gland, and the adrenal glands. Their functioning depends almost entirely on a sequence of cascading chemical signals.

The HPA Structures and Their Chemical Output

The paraventricular nucleus (PVN) of the hypothalamus is a heterogeneous collection of specialized neurons that, when activated by stress, release corticotrophin releasing hormone(CRH) in the bloodstream. The hippocampus is an important component of the negative-feedback regulation of the neuroendocrine stress response.

PituitaryGlandThe pituitary gland or hypophysis is a very small gland (one-third of an inch in diameter and one twentieth of an ounce in weight) located in a bony cavity at the base of the brain, and connected to the hypothalamus by the pituitary stalk. The pituitary two main components are the neurohypophysis that grows from the floor of the hypothalamus, and the adenohypophysis which releases adrenocorticotropic hormone (ACTH). The hormones released by the pituitary exert strong regulatory control over a wide range of bodily functions, including behavior, growth and development, metabolism, salt and water balance, reproduction and immunity. Stress influences the neuroendocrine regulation of a number of pituitary hormones including ACTH, prolactin, growth hormone, luteinizing hormone, thyrotrophin, vasopressin and oxytocin.

The adrenal glands are located in an area that lies dorsal to the kidney and release the glucocorticoid cortisol or corticosterone.

The HPA’s Starring Role in Stress Regulation

The appropriate functioning of the HPA axis is absolutely vital for species survival in humans and in all vertebrates. The HPA axis functions as a closed-loop system involving tight negative-feedback control regulated by the glucocorticoids. Automatic regulation of the HPA axis is essential for ensuring that the stress reaction is terminated after the stressor subsides, thus preventing continuous excessive activation and a healthy return to internal homeostasis.

How the HPA Responds to Acute and Chronic Stress

Most stressors affecting human life can be classified as either systemic or neurogenic stressors. Systemic stressors include all physical stressors that are a challenge to physical well-being and integrity of the body. Neurogenic stressors include those stressful stimuli that have a predominantly emotional or psychological component, such as fear or anxiety.

Exposure to acute stressors produces an immediate and intense activation of the HPA axis which results in enhanced secretion of ACTH and glucocorticoids. The HPA axis responds to the intensity of each individual stressor, in such a way that repeated or intensified stress results in increased secretion of the stress hormones. Regardless of the type of stimuli that cause an acute stress reaction, the removal of the stressor produces the return of HPA-axis activity to baseline or homeostasis.

In chronic or long-lasting stress, the exact mechanisms that produce long-term activity of the HPA axis and the near-continuous secretion of stress hormones remain largely unknown. However, numerous studies have revealed that the de-activating sequences essential to the maintenance of HPA axis integrity, including negative-feedback control, become dysregulated by prolonged stress stimulation.

Most researchers agree on the hypothesis that a defective over-activation of the HPA axis and the associated excessive secretion of powerful glucocorticoids can cause prolonged suppression of the immune system and dysregulation of immune cells, ultimately predisposing the chronically stressed individual to autoimmune disease. On the other side of the equation, the under-activation of the HPA axis has significant implications for our ability to recognize threats and be able to react to them accordingly.

Discovery: A New Brain Pathway for Stress

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In many individuals, a major stressor activates a critical and previously unknown pathway in the brain that regulates anxiety in response to traumatic events. The amygdala, which is the emotional center of the brain, reacts to the stressor by increasing production of the protein neuropsin. The release of neuropsin activates a series of chemical events  that further stimulate amygdala activity, which in turn activates a gene that determines the stress response at a cellular level. Due to this gene activation, these individuals develop long-term anxiety and a typical anxious response to real or perceived stressors.

A study just published in the journal Nature for the first time clarifies the mechanism whereby, in certain individuals and not in others, the extracellular proteolysis triggered by fear-associated responses facilitates neuronal plasticity at the neuron–matrix interface. This process centers around the activity of the serine protease neuropsin, which is critical for stress-related plasticity in the amygdala. Neuropsin determines the dynamics of the EphB2–NMDA-receptor interaction, the expression of the “anxiety gene” Fkbp5 and the triggering of anxiety-like behavior. When faced with a stressor, individuals who are neuropsin-deficient show a much less frequent expression of the Fkbp5 gene and low anxiety. On the other hand, the behavioral response to stress in individuals who are rich in neuropsin shows a more frequent expression of the Fkbp5 gene and much more significant anxiety-related behavior. The researchers, consisting of a team of neuroscientists at the University of Leicester, UK, in collaboration with researchers from Poland and Japan, conclude that their findings establish a novel neuronal pathway linking stress-induced proteolysis of EphB2 in the amygdala to the development of an anxiety-driven response to stress.

Stress-related disorders affect a large percentage of the population and generate an enormous personal, social and economic impact. It was previously known that certain individuals are more susceptible to detrimental effects of stress than others. Although the majority of us experience traumatic events, only some develop stress-associated psychiatric disorders such as depression, anxiety or posttraumatic stress disorder… We asked: What is the molecular basis of anxiety in response to noxious stimuli? How are stress-related environmental signals translated into proper behavioral responses? To investigate these problems we used a combination of genetic, molecular, electrophysiological and behavioral approaches. This resulted in the discovery of a critical, previously unknown pathway. –Dr. Robert Pawlak, University of Leicester.

The study took four years to complete and it sought to examine the behavioral consequences of a series of cellular events caused by stress in the amygdala. They discovered that when certain proteins produced by the amygdala were blocked, either via medication or by gene therapy, the study subjects did not exhibit the highly anxious traits.

This is a significant discovery for the study and treatment of maladaptive stress responses that result in anxiety. By knowing which chemicals along the neuropsin pathway are present in the human brain at the moment of traumatic events, the researchers believe that it will be possible to design intervention therapies for controlling stress-induced behaviors and for the prevention and treatment of stress-related psychiatric disorders such as depression and posttraumatic stress disorder.

Optogenetics Discovers Brain Anxiety Circuit

AmygdCingGyrusThe state of heightened apprehension and high arousal in the absence of immediate threat—commonly labeled as acute stress or anxiety—can be a severely debilitating condition. Over 28% of the population suffers from anxiety disorders that contribute to the development of major depressive disorder and substance abuse. Of all the structures of the limbic system, the seat of emotion processing, the amygdala plays a key role in anxiety, although by what exact mechanism still remains unclear. Newly published research carried out by a group of neuroscientists at Stanford University using the novel technique of optogenetics with two-photon microscopy has permitted a much closer exploration of the neural circuits underlying anxiety than ever before. The optogenetics approach facilitates the identification not only of cell types but also the specific connections between cells. The researchers noticed that timed optogenetic stimulation of the basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA) produced a significant, acute, and reversible anxiety-reducing effect. Conversely, selective optogenetic inhibition of the same projection resulted in increased anxiety-related behaviors. These results indicate that specific BLA–CeA projections are the critical circuit elements for acute anxiety control in the brain. The results were published in the March 17 issue of the scientific journal Nature.

A Closer Look at the Amygdala’s BLA and CeA Regions

BasolateralAmygdalaThe amygdalae (amygdaloid nucleus) are two identical almond-shaped brain structures located in each temporal lobe. Each amygdala receives input from the olfactory system, as well as from visceral structures. The amygdala in humans has been confirmed by functional MRI imaging to be the area of the brain that is best correlated with emotional reactions and plays a key role in the brain’s integration of emotional meaning with perception and experience. The emotional aspect of the response of the individual is passed on to the frontal cortex, where “decisions” are made regarding possible responses. In this way, the response of the individual can take into account the emotional aspect of the situation.

Additionally, the amygdala coordinates the actions of the autonomic and endocrine systems and prompts release of adrenaline and other excitatory hormones into the bloodstream. The amygdala is involved in producing and responding to nonverbal signs of anger, avoidance, defensiveness, and fear. The amygdala has been implicated in emotional dysregulation, aggressive behavior, and psychiatric illnesses such as depression. It has also been shown to play an important role in the formation of emotional memory and in temporal lobe epilepsy.

The basolateral amygdala, one of the two structures studied in the recent Stanford research, receives extensive projections from areas of the brain cortex that are specialized for recognizing objects such as faces in central vision. Extensive intrinsic connections within the amygdala
promote further coordination of sensory information.

Biological effects initiated by amygdala include increases or decreases in arterial pressure and heart rate, gastrointestinal motility and secretion, evacuation, pupillary dilation, piloerection, and secretion of various anterior pituitary hormones, especially the gonadotropins and
adrenocorticotropic hormone, which are key agents in the stress reaction. Interestingly, amygdala stimulation can also cause several types of involuntary movement, such as raising the head or bending the body, circling movements, occasionally rhythmical movements, and movements
associated with taste and eating, such as licking, chewing, and swallowing.

LimbicSystemGeographyThe findings also show the involvement of the amygdala’s CeA region in mediating threat-related anxiety and acute fear-related behavioral and hormonal responses. Earlier studies had shown that stimulation of this same area reduces snake fear and pituitary-adrenal activity and that CeA lesions resulted in decreased expression of threat-induced freezing. Additionally, the CeA region of the amygdala was reported as being significantly involved in the consolidation of contextual fear memory, i.e., what permits us to remember so vividly and persistently objects or situations that have caused fear in us in the past.

Gene Found to Mediate Stress and Depression

PearlHarbor_EN-US3308869662The serotonin transporter promoter polymorphism 5-HTTLPR region of gene SLC6A4, one of the over 1,000 genes located on human chromosome 17, has been positively identified as the moderator of the relationship between stress and depression. A new, extensive analysis of 54 studies of more than 40,000 individuals was recently completed at the University of Wurzburg, Germany, finding “strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the s [short] allele associated with an increased risk of developing depression under stress.”

The meta-analysis of the 54 studies looked at 40,749 individuals stratified into subgroups according to specific types of stressors. They found a statistically significant relationship between the presence of the short allele of 5-HTTLPR in the individual’s gene and increased stress sensitivity in two of the subgroups: the subgroup of individuals who had suffered childhood maltreatment and the subgroup of individuals who developed a specific stress-related medical condition.

Despite some analytical limitations due to the variety of sources and methods within the 54 original studies, the authors of the meta-analysis conclude that, “the present study suggests that there is cumulative and replicable evidence that 5-HTTLPR moderates the relationship between stress and depression. Our evidence, particularly the identification of important study characteristics that influence study outcome (stressor type and stress assessment method), can provide guidance for the design of future gene x environment interaction studies.”

This new study, already published online and scheduled to appear in the January 2011 edition of the Archives of General Psychiatry, disconfirms the findings of 2 earlier and much less extensive studies, which had found no evidence of the interaction. The authors of the new study speculate that the earlier negative findings may have been due to the small number of cases analyzed, the authors’ inability to obtain primary data for many of the studies, and the inclusion only of studies that looked at stressful life events (SLEs), and not other stressors such as childhood maltreatment.

More On 5-HTTLPR and Serotonin

5HTTLPR-Chromosome_17_svgSince its discovery in the 1990s, polymorphic region 5-HTTLPR located on SLC6A4, the gene that codes for the serotonin transporter, has received intense investigation for its possible role in stress and other mental health issues, especially mood disorders. A 2000 study uncovered evidence that 5-HTTLPR may be involved in the appearance of certain anxiety-related personality traits, and a 2003 study presented evidence that 5-HTTLPR may also be involved in the development of childhood anxiety and shyness.

Serotonin is a small-molecule indoleamine neurotransmitter that plays an important role in mood, depression and anxiety, and is also implicated in the sleep/wake cycle. Serotonin, after being released in the raphe nuclei of the brain stem and other parts of the body and having its effect on mood, is routinely removed from the synaptic cleft by the reuptake of the transmitter with the serotonin transporter. It is the blocking of this reuptake that results in the therapeutic effect of SSRI (selective serotonin reuptake inhibitor) antidepressant medications, such as Lexapro, Paxil, Zoloft, and Prozac.

The Cardiopsychology of Stress

Happy2011What effect does psychological stress have on cardiovascular physiology? Does psychological stress contribute to cardiovascular disease? These important questions are the domain of cardiopsychology, the discipline that studies how psychosocial stressors impact the onset, course, rehabilitation and the illness processing (coping) of cardiac diseases. In this post, we look at the effects of stress on the normal heart in healthy condition, and the effects of acute or chronic stress on individuals with cardiovascular disease.

{tab=Overview}
Tuvalu_EN-US163122471The body responds to stress primarily through the mobilization of resources initiated by the autonomic nervous system and endocrine activity. Endocrine activity consists of sympathetic adrenomedullary, pituitary-adrenocortical, and thyroid responses. The most important stress hormones released by sympathetic adrenomedullary response are epinephrine and norepinephrine. The stress hormones released in the pituitary-adrenocortical response are adrenocorticotrophic hormone (ACTH) and cortisol.

Psychological conditions shown to have an effect on cardiovascular disease include anxiety disorders, panic disorders, and depressive disorders. There is compelling evidence that acute psychological stress triggers major autonomic cardiovascular responses and cardiac events. Nonetheless, the evidence that chronic stress causes cardiovascular disease is highly controversial. Although the most prevalent opinion among cardiologists, psychiatrists, physiologists, and psychologists is that psychological stress has an effect on cardiovascular disease, these effects are not easily quantifiable or attributable with any degree of precision. What we do know is that acute stress is often accompanied by cardiovascular changes, some of which can be dangerous to certain individuals.

Data on whether chronic stress may, over time, cause cardiovascular disease are less convincing. For example, there is little validated evidence that people with anxiety-related disorders have a higher prevalence of cardiovascular disease than their less anxious counterparts. Moreover, except for postmyocardial infarction depression, there is insufficient evidence that individuals with cardiovascular disease have a higher prevalence of psychological disorders than those who have no cardiovascular disease.

{tab=Normal Heart}
MaldiveAtolls_EN-US1893647453Acute mental stress alters baseline parameters on the normal heart and vascular system in good health condition. Under acute stress, it is quite normal for blood pressure to rise, due to the action of neural mechanisms that regulate stress-induced blood pressure changes as a stress reaction to a dangerous situation that requires an increase in cardiac activity.

Structures of the central nervous system involved in this rapid arousal include the medulla oblongata, the medial geniculate body, the limbic system (amygdala and hypothalamus), and the brainstem. Psychological stress-induced changes in blood pressure are usually predictable and can vary depending on many variables, including duration of stress, time of measurement, expectations, psychological preparedness, and individual background.

Specific effects of psychological stress on the cardiovascular system are increased cardiac output, higher stroke volume, stronger forearm blood flow, increased left ventricular ejection fraction, higher peripheral vascular resistance, and increased cardiac microcirculation. These effects are not dangerous on the normal heart and vessels in good health condition, and they generally subside and return to normal levels after the stressor has passed.

{tab=Acute Stress}
SnowyChristmas_EN-US2022031457As in the healthy heart, acute stress increases blood pressure (generally by 10–20% and sometimes to hypertensive levels) in individuals with cardiovascular disease. Acute stress also increases the heart rate of individuals with cardiovascular disease, and angina pectoris and ischemia may result from this increase in heart rate. In some cases, the stress-induced increase in heart rate also alters cardiac electrical stability and may cause life-threatening arrhythmias.

Acute stress may also cause coronary artery vasoconstriction, reduce left ventricular ejection fraction, and induce or exacerbate left ventricular wall motion abnormalities in individuals with cardiovascular disease. In this respect, studies have shown that frequent anger among individuals with cardiovascular disease may increase their vulnerability to cardiac complications.

Psychological stress produces strong limbic-hypothalamic activity, which may contribute to the yet unclear etiology of essential hypertension, i.e. high blood pressure that does not appear to have specific organic causes. Conversely, the presence of hypertension, borderline hypertension, and genetic risk for hypertension may have an impact on blood pressure reactivity to psychological stress, thus setting up an apparent circular causality between stress-hypertension-higher reactivity to stress.

Individuals with high blood pressure are characterized by a greater arterial wall-to-lumen ratios compared with healthy individuals. Thus, the same quantity of norepinephrine causes a greater increase in peripheral vascular resistance compared to healthy individuals who have a smaller arterial wall-to-lumen ratio. Also, individuals who are already suffering from angina pectoris react to stress with a greater elevation of blood pressure.

{tab=Chronic Stress}
KugaCanyon_EN-US1699950676Chronic stress and prolonged bereavement have been shown to increase the risk of cardiac death. A large-scale study showed that stress due to the death of the wife caused a 40% increase in the death rate of the surviving husbands during the first 6 months of loss, with two-thirds of those deaths attributable to cardiovascular disease. A similar increases did not occur among widows following the death of their husbands.

Studies conducted on individuals who exhibit type A and type B personality patterns have tested the hypothesis that personality may affect the inset, course, and outcome of cardiovascular disease. Type A personalities are those characterized by time-urgency, high competitiveness, ambitiousness, and frequent hostility. Type B personalities are unhurried, more relaxed, and less competitive. The results of these studies show that if there is a correlation between personality patterns and cardiovascular disease, this correlation is very weak. Thus, type A or type B personalities appear to have similar outcomes in the convergence of stress and cardiovascular disease.

Anxiety is a significant factor in producing chest pain even when coronary arteriography is normal, and anxiety disorders have been confirmed as a debilitating factor. Major depressive disorder is the second significant factor, and this disorder appears to predict future cardiac events among patients with coronary artery disease. Chronic anxiety, helplessness, and depression have been specifically linked to angina pectoris and sudden death by cardiac arrest. More than 300,000 Americans experience sudden (within minutes) death each year. Excluding acute myocardial infarction-induced ventricular arrhythmias, about one in ten sudden deaths are due to cardiac arrhythmias (particularly ventricular arrhythmias).

Research by Rahe and others on the health impact of significant life changes discovered that individuals who suffer a myocardial infarction are more likely to have had a major life change during the 6 months preceding the heart attack. In another study, Rahe and Lind provided evidence that life change occurs more frequently among victims of sudden cardiac death compared with survivors of myocardial infarction.

The relationship between chronic psychological stress and hypertension remains controversial. Psychological stress-induced increases in heart rate and blood pressure reactivity do have an immediate effect on blood pressure readings. Nonetheless, this clearly demonstrable increase in blood pressure following a sudden and significant stressor does not appear to carry on to produce long-term effects on blood pressure.

In summary, the extent of coronary artery disease, the degree of left ventricular dysfunction, and the presence of arrhythmias appear to determine individual vulnerability to stress-induced sudden cardiac death. When individuals are already suffering from advanced cardiovascular disease, stress-related precipitants of sudden cardiac death are ubiquitous and may be impossible to avoid. Acute stressors often contributing to sudden cardiac death include bereavement, unemployment, financial distress, dislocation, lower education levels, individual responses to psychological stress, and social isolation. Research results are somewhat contradictory in establishing a clear association between cardiovascular disease and such factors as gender, personality patterns, anxiety, panic disorder, PTSD, bereavement, depression, and occupation.

{tab=References}
REFERENCES
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2. Culic V, Eterovic D, Miric D. Meta-analysis of possible external triggers of acute myocardial infarction. Int J Cardiol 2005;99:1– 8.
3. Kloner RA. Natural and unnatural triggers of myocardial infarction. Prog Cardiovasc Dis 2006;48:285–300.
4. Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol 2007;49:1230 –50.
5. Smith SC Jr., Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol 2006;47:2130 –9.
6. Bhattacharyya MR, Steptoe A. Emotional triggers of acute coronary syndromes: strength of evidence, biological processes, and clinical implications. Prog Cardiovasc Dis 2007;49:353– 65.
7. Davidson KW. Emotional predictors and behavioral triggers of acute coronary syndrome. Cleve Clin J Med 2008;75 Suppl 2:S15–9.
8. Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005;45:637–51.
9. Strike PC, Steptoe A. Behavioral and emotional triggers of acute coronary syndromes: a systematic review and critique. Psychosom Med 2005;67:179–86.
10. Strike PC, Magid K, Whitehead DL, Brydon L, Bhattachatyya MR, Steptoe A. Pathophysiological processes underlying emotional triggering of acute cardiac events. Proc Natl Acad Sci U S A 2006;103:4322–7.
11. Thrall G, Lane D, Carroll D, Lip GY. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: implications for the pathogenesis of acute coronary syndromes. Thromb Res 2007;120:819–47.
12. Tofler GH, Muller JE. Triggering of acute cardiovascular disease and potential preventive strategies. Circulation 2006;114:1863–72.
13. Rahe, R., & Lind, E. (1971). Psychosocial factors and sudden cardiac death: a pilot study. Journal of Psychosomatic Research, 15(1), 19.

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Stress Hardware Review: Anterior Cingulate

Dolomites_EN-US3033597177The anterior cingulate cortex is a region of the brain that is activated by sensation, cognition, and emotion. It appears to play an important role in autonomic, affective, and cognitive behavior. Because of its position, the anterior cingulate is anatomically and functionally well positioned to integrate information across the physical, intellectual and emotional domains. Important in the stress reaction, the anterior cingulate region is activated during self-regulation of arousal through its connections with the cholinergic basal forebrain. The whole structure, but especially area 32, produces inhibitory inputs that decrease amygdala responsiveness and are helpful in mitigating the effects of fear and in preventing or at least delaying “amygdala hijacks.”

The normal functioning of the anterior cingulate area leads to a normal response to stressful events, which is a psychophysiological arousal or increased emotionality. The normality of the brain response to traumatic stimuli also serves to inhibit feelings of fear when there is no true threat.  Any chemical or structural failure of activation in this area and/or decreased blood flow in the adjacent subcallosal gyrus can lead to an exaggerated response to stress, resulting in significantly higher emotionality and the inability to properly regulate fear. The latter condition provides the inducing cues in anxiety disorders, i.e. increased and persistent fearfulness that is not appropriate for the context.

What the Anterior Cingulate Does

BrodmanBrainAreasPhysically, stimulation of the anterior cingulate (especially in area 24) induces changes in blood pressure, heart rate, respiratory rate, pupillary dilation, skin conductance, thermoregulation, gastrointestinal motility, and changes in adrenal cortical hormone secretion (ACTH). Cognitively, the anterior cingulate cortex plays a leading role in learning new behaviors, whether as a conditioned response to predictors of painful stimuli, as an instrumental response to avoid such stimuli, or in response to reduced reward. Emotionally, the anterior cingulate (along with other structures in the limbic system) mediates emotional responses including fear, agitation, and euphoria, and verbal expression with affective content, such as sighs, cries, and screams.

Neuroimaging studies with powerful fMRI instruments show electrical activation in the rostral–ventral anterior cingulate cortex when individuals under study are asked to recall sad memories or view faces with sad expressions, when they are told to anticipate an upcoming painful electric shock, and when exposed to scenes or words with emotional content. It should come as no surprise that stress-induced activations in the amygdala and orbitofrontal cortex occur simultaneously with those in the anterior cingulate cortex.

Genes, Stress and the Anterior Cingulate

Genetic studies have conclusively demonstrated that the anterior cingulate cortex is highly sensitive to environmental stressors, either physical, psychological, or behavioral. Anoxia (lack of oxygen), maternal separation, amyloid protein expression, and drug abuse all induce hypometabolism, gliosis, and programmed cell death in the anterior cingulate cortex. After prolonged and continued exposure to stress, nerve cells in the anterior cingulate cortex are damaged and killed by excessive stimulation, a process called excitotoxicity.

When the Anterior Cingulate Malfunctions

Several psychiatric disorders are linked with abnormalities in the function of the anterior cingulate cortex. Significantly elevated neurochemical activity in this region of the brain has been observed in obsessive–compulsive disorder, tic disorder, and depression. A normal range of activity is restored with behavioral and pharmacological treatment of these disorders. Other psychiatric disorders that have been associated with abnormal functioning of the anterior cingulate cortex include attention deficit hyperactivity disorder (ADHD) and schizophrenia.

Stress Hardware Update: Limbic System 2.0

LimbicSystemGeographyThe term limbic system designates the entire neuronal circuitry and forebrain structures that control emotional behavior, motivational drives and the processing of present and past sensory experiences. The brain structures of the limbic system are located around the middle edge of the brain. Several limbic structures are involved in determining the affective nature of sensory inputs, i.e., whether the sensations are pleasant or unpleasant. The emotional qualities we attach to the input provided by our five senses are also called reward (when they are pleasing to us and therefore we crave more of them) or punishment (when they are unpleasant and therefore we seek to avoid them), or satisfaction or aversion. Neurobiological research on the functions of the limbic system dating back to its XIX century pioneer Pierre-Paul Broca (1861), later expanded by James Papez (1937), Giuseppe Moruzzi and Horace Magoun (1949), and Ross MacLean (1949, 1952) identified the “reticular” and “limbic” systems as regulating the energizing and expressive roles in the central nervous system.

The limbic system is comprised of numerous structures, the most important of which are the hypothalamus, the amygdala, the hippocampus, the cortex, the cingulate gyrus, the striatum, the pallidum, the thalamus, and Meynert’s nucleus basalis. Each of these structures performs a specific function, and often also serves to receive, transmit and amplify communication within the limbic system, with other areas of the brain, and with other parts of the central nervous system.

The Hypothalamus: The Central Autonomic Controller

A major component of the limbic system is the hypothalamus and its related substructures. The hypothalamus complex controls the internal state of the body, such as temperature, osmolality of the body fluids, appetite and thirst and the regulation of body weight. Despite its very small size of only a few cubic centimeters (which represents less than 1% of the brain mass), the hypothalamic complex has two-way communicating pathways with all levels of the limbic system and is the key structure for higher level coordination of autonomic and endocrine functions. There would not be a stress reaction, with its almost instantaneous activation of physical and psychological defense mechanisms, without the hypothalamus providing the critical signal activation.

The Amygdala: The CPU of Emotional Response

AmygdCingGyrusThe amygdala is a group of nuclei embedded in the anteromedial temporal lobe, which receives input from all five senses. It performs the analysis of form and color and facilitates the recognition of complex stimuli such as human faces. The amygdala can influence heart rate and blood pressure, gut and bowel function, respiratory function, bladder function, and many more instinctive physical reactions. It is in the amygdala and its connection to other limbic structures that the determination of the affective value of sensory stimuli (rewarding or aversive) is made and our mood (or feelings about something) is determined. Stimulation of the amygdala produces the defense reaction that prepares us for fight, flight or freeze, along with complex sensory and experiential phenomena, which may include fear, sensory hallucinations, feelings of deja vu, and memory-related flashbacks and nightmares. The amygdala receives neuronal signals from all portions of the limbic cortex and is the “central processing unit” in which the limbic system produces an emotional response to events, people and situations. The amygdala also interacts with higher brain regions that govern such processes as directed attention, declarative memory, and response inhibition (Davidson, Putnam, & Larson, 2000; LeDoux, 1995).

The Hippocampus: Memory Chips and Orientation

The hippocampus is a highly specialized region of the cerebral cortex, which along with surrounding areas of the parahippocampal gyrus is directly involved in memory processing and spatial orientation. The hippocampus provides the neural mechanism for association of different parameters that is necessary for the moment-to-moment incorporation of experience into our short- and long-term memory banks. Almost any type of input from the five senses causes activation of at least part of the hippocampus, which in turn distributes many outgoing signals to the anterior thalamus, to the hypothalamus, and to other parts of the limbic system, especially through the fornix, a major communicating pathway.

The Orbital and Medial Prefrontal Cortex: Food and Personality

PhineasGageThe cortical areas of the limbic system are divided into two interconnected networks with related but distinct functions. Many of these functions are related to food or eating (e.g., olfaction, taste, visceral afferents, somatic sensation from the hand and mouth, and vision), and neurons in the orbital cortex respond to multisensory stimuli involving the appearance, texture, or flavor of food. Therefore, the orbital and medial prefrontal cortex have the function of evaluating feeding-related sensory information and to stimulate appropriate visceral reactions. More importantly, damage to the ventromedial frontal lobe can produce dramatic behavioral changes, which suggests that the visceral reactions evoked through this cortical area are critical in evaluating alternatives and making choices. As the well-publicized 19th-century case of Mr. Phineas Gage’s accidental head impaling by a steel rod demonstrates, individuals with damage to the ventromedial prefrontal cortex have no problem with their motor or sensory function, their intelligence or cognitive function, but show devastating changes in personality and choice behavior.

The Cingulate Gyrus: The Cement of Society

Intriguing data and ideas have been proposed by several researchers seeking to identify specific functions of the cingulate gyrus. In what has been termed the affiliation/attachment drive theory, Everly (1988) has shown experimentally that the removal of the cingulate gyrus eliminates both affiliative and grooming behaviors. MacLean (1985) has argued that the affiliative drive may be hard-coded in the limbic system and may be the anatomical underpinning of the “concept of family” in humans and primates. The drive toward other-oriented behaviors, such as attachment, nurturing, affection, reliability, and collaborative play, which has been referred to as the “cement of society” (Henry and Stephens, 1977), appears to originate in this relatively small limbic system structure.

The Ventromedial Striatum, Ventral Pallidum, and Medial Thalamus

The nuclei of the ventromedial striatum are also related to reward and reward-related behavior, whereby they inhibit or suppress unwanted behaviors while allowing other behaviors to be freely expressed. The dorsolateral striatum and related areas of the globus pallidus appear to be involved in switching between different patterns of motor behavior, whereas the ventromedial striatum and pallidum may allow changing of stimulus–reward associations when the reward value of a stimulus has changed. These areas are examples of the complexity and redundancies built into limbic system structures that permit multiple iterations of signal transmission and reception, and a much more complex and refined analysis of sensory inputs from the five senses.

Nucleus Basalis (of Meynert)

The nucleus basalis of Meynert is a prominent group of large cells located in the basal forebrain, most of which are involved in the activation of acetylcholine or GABA neurotransmitters, indispensable in activation of the stress reaction and our defense mechanism when a physical or psychological threat is perceived. The magnocellular basal forebrain nuclei are well situated to modulate brain activity in relation to limbic activity.

Disorders of the Limbic System

Although lesions to limbic structures do not necessarily result in sensory or motor deficits, any loss of function in these structures is usually associated with a variety of psychological problems, including depression, bipolar disorder, obsessive–compulsive disorder, and schizophrenia.

Structural changes have been noted in the hippocampal formation, medial thalamus, and prefrontal cortex in schizophrenic subjects. Images obtained through positron emission tomography scans show that the amygdala, prefrontal cortex and medial thalamus are abnormally active in patients suffering from severe unipolar and bipolar depression.

The complete removal of the amygdala and other nearby structures in laboratory settings causes specific changes in animal behavior called the Klüver-Bucy syndrome, whose characteristic symptoms are a complete lack of fear of anything, extreme curiosity about everything, rapid loss of short-term memory, tendency to place everything in the mouth and sometimes even trying to eat solid objects, and a sex drive so strong that it leads to attempts to copulate with immature animals, animals of the wrong sex, or even animals of a different species. Although similar lesions in human beings are rare, afflicted people respond in a manner not too different from that of the affected animal.

When Stress Hurts: Neurochemistry Cognates

In this third post in the series on the close association between psychological stress and psychogenic pain, we take a look at neurochemical substances that are involved in the process of psychogenic pain generation and reaction to psychological stress.

The Neurochemistry of Pain: Substance P

aaGiotto_DeposizioneSubstance P, discovered in the 1950s, is the quintessential pain neurochemical, which is activated in response to physiological pain as well as to psychological stress (DeVane, 2001). It is a prototypic neuropeptide of the tachykinin family that has been linked to the production of over 50 neuroactive chemical substances (Brain & Cox, 2006). Its best documented role is as the modulator of signals to nociceptive neurons that communicate the intensity of noxious or adverse stimuli, not only those caused by pain but also those produced by psychological stress (DeVane, 2001; Shaikh, Steinberg, & Siegel, 1993). Substance P receptors are found throughout the CNS but especially in the substantia gelatinosa of the dorsal horn, which is the first point of arrival of afferent pain signals to primary nociceptive fibers.

It is not coincidental that Substance P is also present in the limbic system of the CNS, in the hypothalamus and in the amygdala, all structures that are closely associated with the perception and processing of emotions (Bannon et al., 1983; Culman & Unger, 1995; DeVane, 2001; Stahl, 1999).

Some purely psychological and psychogenic reactions of the organism also see the involvement of substance P, such as the vomiting reflex, anger and defensive behaviors (Krase, Koch, & Schnitzler, 1994), changes in cardiovascular tone (Black & Garbutt, 2002), stimulation of salivary secretions, and other physiological responses that are associated with the general adaptation of the body (Selye & Fortier, 1950) to stressful stimulation.

Kohlmann and colleagues (1997) reported the discovery of substance P in blood pressure regulation in individuals with essential hypertension, a condition that has been related to maladaptive responses to stress (Palomo et al., 2003) and has been shown to respond to psychotherapeutic interventions (Amigo, Buceta, Becona, & Bueno, 1991). Other evidence of the concurrent role of substance P in signaling pain and in the stress reaction comes from animal studies that show an array of defensive behavioral and cardiovascular changes in animals subjected to stressful stimulation (Krase et al., 1994), as well as the detection of substance P in the amygdala of laboratory animals upon neonatal separation (Kramer et al., 1998).

The Neurochemistry of Stress

The neuroendocrine response to a real or perceived stressor consists of the near simultaneous release by the sympathetic nervous system (SNS) of the catecholamines norepinephrine (NE) and epinephrine, the release by the hypothalamus of corticotrophin releasing hormone (CRH), the inhibition by the hypothalamus of gonadotropin releasing hormone (GnRH) and pituitary gonadotropins, the release by the pituitary gland of prolactin (PRL), and the release by the pancreas of glucagon (Sapolsky et al., 2000).

Upon release of NE into the synaptic cleft, approximately 10% of it enters the plasma, thus making plasma NE levels one of the most reliable measures of SNS activity and the magnitude of the body’s response to stressors. Peroutka (2004) has proposed that a migraine attack may be triggered by a significant decrease of NE due to the excessive or prolonged release of adenosine, dopamine and prostaglandin by the over-stimulated SNS. Since sympathetic activation is the primary component of the stress response, stress is thus unequivocally linked to the onset and maintenance of migraine headaches.

The Closest Association: Stress-Induced Analgesia

Livingstone_LionRThe body’s reactivity to real or perceived stressors provokes measurable changes in the autonomic nervous system (ANS) and in the structures controlled by the hypothalamic-pituitary-adrenal (HPA) axis. These changes include blood pressure elevation, pupil dilation, and secretion of cortisol. In the presence of a significant stressor, the stress response also includes a “stress induced analgesia,” or a decreased sensitivity to further pain (as writer-explorer David Livingstone so eloquently reported). This antinociceptive action of the ANS translates into an inverse relationship between blood pressure and pain sensitivity in animals and humans, and is designed to maintain the integrity of the body’s defense systems. Additionally, the release of CRF by the hypothalamus has known analgesic effects (Okifuji & Turk, 2002).

The ANS was recognized by Cannon (1914; Cannon, 1933) as the originator and enabler of the “fight or flight” response to stress. Stress-related releases of adrenaline stimulate the feedback provided by the afferent and efferent vagal fibers. Once again, these same fibers are involved in the activation of endogenous pain modulation centers (Bielefeldt, Christianson, & Davis, 2005). Pain and stress just seem to go together.

Previously in this series:

Next:

  • Psychological Stressors and the Sudden Appearance of Psychogenic Pain
  • Fibromyalgia, Severe Headaches and Other Stress-Related Misery
  • Medical and Non-Medical Treatments for Stress and Psychogenic Pain

When Stress Hurts: Central Nervous System

In establishing the connection between the onset of psychogenic pain and stress, it is important to notice that pain and stress share the same central nervous system (CNS) pathways and structures. In this second post in the series on the close association between psychological stress and psychogenic pain, we’ll take a look at these shared structures.

CNS Structures Mobilized by Pain and Stress

PendulumThe body’s response to pain engages a large number of CNS structures that are often the same as the ones activated by the stress reaction. The afferent pathways that carry pain signals connect to the thalamic nuclei and from there to the somatosensory, insular and anterior cingulate (ACC) portions of the brain cortex. A recent functional MRI (fMRI) study (Keltner et al., 2006) on the effects of pain expectation on pain transmission provides the best evidence for the activation of the rostral ACC (rACC), periaqueductal gray (PAG), and medial prefrontal cortex. This and other imaging studies provide evidence of a bidirectional pain pathway receiving input from the limbic system and the amygdala, converging on the PAG, traveling through the pontomedullar nuclei, and controlling spinal pain transmission neurons (Fields, 2000; Fields & Martin, 2001). As the authors of this study point out, “expectation for a higher intensity noxious stimulus increases subjectively experienced pain intensity in part through the action of a descending pathway that facilitates nociceptive transmission at and/or caudal to the region of the contralateral nucleus cuneiformis (nCF)” (p. 4442). The nCF, in humans and other primates, has a composition similar to the PAG and its neurons project directly into the rostroventral medulla, the hypothalamus and the amygdala, all structures directly involved in modulation of the stress reaction.

PMR_muscle-crampsLikewise, the body’s stress response engages a large number of the same CNS structures, specifically certain subregions of the hypothalamus such as the paraventricular nucleus (PVN), the amygdala, and the periaqueductal grey; and certain cortical brain structures, such as the medial prefrontal cortex and subregions of the anterior cingulate and insular cortices (Maier, 2003). These structures provide output to the pituitary and pontomedullar nuclei, which in their turn stimulate the body’s neuroendocrine secretions, as well as to the hypothalamic-pituitary-adrenal (HPA) axis, the endogenous pain modulation system, and the ascending aminergic pathways. The feedback controlling the stress response is provided by the serotonergic (raphe) and noradrenergic (locus ceruleus) structures and by the levels of glucocorticoids in the blood stream, which provide inhibitory impulses to the medial prefrontal cortex and to the hippocampus. Corticotrophin releasing hormone (CRH) is the fundamental chemical substances mediating the stress response, which is secreted by PVN, amygdala, and locus ceruleus neurons. Acute or chronic stress can temporarily or permanently modify the level of responsiveness and output of the CNS to stress (Bennett et al., 1998).

Sharing Pathways, Sharing Outcomes

With this significant convergence of pathways, neurochemical activity and CNS structure activation, it should come as no surprise that acute stress can provoke physical pain, often in the head, the muscles, and the abdominal region. Equally unsurprising is that pain, especially when sharp and unexpected, is in itself a cause of stress that mobilizes the body into immediate action (think of the hand that immediately goes to cover the cut or the burn). Continuous pain, of any origin, is inherently stressful. Continuous stress can be, and often is, manifested by otherwise unexplained (thus psychogenic) physical pain.

Previously in this series: When Stress Hurts: Psychogenic Pain

Next:

  • The Neurochemistry of Psychogenic Pain and Stress
  • Psychological Stressors and the Sudden Appearance of Psychogenic Pain
  • Fibromyalgia, Severe Headaches and Other Stress-Related Misery
  • Medical and Non-Medical Treatments for Stress and Psychogenic Pain

Can Environmental Stress Control Our Genes?

A_coign_of_vantage Environmental stress can destroy protective complexes in human cells and turn on or off selected genes, newly published research shows. External stress agents appear to “instruct” certain enzymes to modify gene behavior, whereby genes that should remain turned off are activated and disturb the development, functioning and growth of human cells. According to Dr. Simmi Gehani, principal researcher at the University of Copenhagen where the study was conducted, this means that external stress factors can control the activity of our genes.

Why is this important? The specific knowledge of how our genes are regulated is important in order to understand how stress can lead to development of disease. The genetic code contained in our DNA is the same as in the over 200 cell types found in our body. Based on the “instructions” contained in our DNA, individual cells develop in different and highly specialized ways. Many genes are only active at specific times during fetal development or in specific cell types in the adult body. The natural deactivation of certain genes at specific time points ensures normal development and maintains proper cellular identity and function.

The new research findings, published in the latest edition of Molecular Cell, show that stress-activating factors can turn on genes that were supposed to remain inactive. These external stress factors are pollution, tobacco smoke, alcohol, drugs, chemical contaminants, or bacterial toxins. They can put a significant stress load on cells, which must react to survive and maintain their normal function. These research findings may help explain the effects that environmental stressors can have on health and functioning.

Additionally, they may also explain the dangers of external stressors to the unborn. During fetal development, exposing human cells to a stress-activating agent can turn on previously inactive genes. This is significant because even small changes in gene activation can have disastrous effects in child development.

There is a widespread belief — often dismissed — that what happens during pregnancy can affect everything that a person becomes in life. This and other research, writes Annie Murphy Paul in her new book Origins: How the Nine Months Before Birth Shape the Rest of Our Lives, may provide evidence to support the claim.

Stress Hardware Reviews: The Hippocampus

clip_image001What brain structures rouse us from inactivity and set in motion our defense mechanisms when a stressor is perceived? Predictably, the brain’s older and more primordial area, the so-called animal brain, where the hypothalamus, the amygdala, the hippocampus, the septum area, the basal ganglia and the thalamus are located. These structures, collectively called the limbic system, are interconnected and work together to initiate motor and other functional activities of the brain that mobilize the body. In this post about stress hardware, we discuss the hippocampus.

Virtually any experience perceived by the five senses appears to cause the activation of at least some part of the hippocampus. The hippocampus in turn redistributes these sensory signals to the thalamus, the hypothalamus, and other parts of the limbic system. Thus, the hippocampus acts as an important switching center through which incoming sensory signals are retransmitted and initiate behavioral reactions for different purposes. Its importance has been demonstrated empirically: experimental artificial stimulation of the hippocampus can induce a wide variety of behavioral patterns such as pleasure, rage, passivity, or excessive sexual drive.

The cells of the hippocampus appear to be especially sensitive to the effects of various stressors. Although not directly involved in the stress response, its ventral regions appear to exercise a regulatory influence on the hypothalamic-pituitary-adrenal (HPA) axis activity and are also a primary target for elevated glucocorticoid levels. The glucocorticoid hormones owe their name to their important effects on blood glucose concentration, which is the principal source of energy of the human cell. They also regulate protein and fat consumption, and the utilization of carbohydrates to produce additional quantities of energy. Cortisol is the principal glucocorticoid. Read more

Stresshack #3: Livingstone, The Lion and Me

 Livingstone_LionRIn going round the end of the hill I saw a lion sitting on a piece of rock about thirty yards off with a little bush in front of him. I took a good aim at him through the bush and fired both barrels into it. The men called out. “He is shot, he is shot.” Others cried, “He has been shot by another man too, let us go to him.” I saw the lion’s tail erected in anger and turning to the people said, “Stop a little till I load again.” When in the act of ramming down the bullets I heard a shout and looking half round I saw the lion in the act of springing upon me. He caught me by the shoulder and we both came to the ground together. Growling horribly he shook me as a terrier dog does a rat. The shock produced a stupor similar to that which seems to be felt by a mouse after the first gripe of the cat. It caused a sort of dreaminess in which there was no sense of pain nor feeling of terror though I was quite conscious of all that was happening. It was like what patients partially under the influence of chloroform describe: they see the operation but do not feel the knife. This placidity is probably produced in all animals killed by the carnivora and if so is a merciful provision of Creator for lessening the pain of death. As he had one paw on the back of my head I turned round to relieve myself of the weight and saw his eyes directed to Mebalwe who was aiming at him from a distance of ten or fifteen yards. His gun which was a flint one missed fire in both barrels. The animal immediately left me to attack him and bit his thigh. Another man whose life I had saved after he had been tossed by a buffalo attempted to spear the lion upon which he turned from Mebalwe and seized this fresh foe by the shoulder. At that moment the bullets the beast had received took effect and he fell down dead.

David Livingstone (1857). Missionary Travels (pp. 11-12). London: EW Cole.

Scottish explorer Livingstone, in his journey to discover the sources of the Nile, reported what is now known as stress-induced analgesia. Under conditions of extreme stress or in the adaptation to an extreme environmental challenge, an individual’s normal reaction to pain—reflex withdrawal, escape, rest, and recuperation—could be disadvantageous. In a dire emergency, these reactions to pain are automatically suppressed in favor of more useful behaviors. It turns out that we have a piece of software, the analgesia system, that automatically activates in these circumstances, with rather remarkable effects.

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Stress Hardware Review: The Amygdala

AmidalaL

There are things I cannot do. I cannot watch my people suffer. I cannot sit when something must be done. I cannot judge those who are different. There are things I cannot do. Run. Hide. Ignore. There are things I cannot do. But there are certainly things I will do!

Padmé Amidala in Star Wars: Clone Wars

One of the most important structures of the brain’s limbic system is the amygdala, which in Queen Amidala’s imaginary brain produced behavior that was characteristically cool and aloof at times, forceful and passionate at others, but always kept in balance by poise and careful deliberation. An exemplar of good stress management.

amygdala The human amygdala is an almond-shaped double  complex (one on each side of the brain) of multiple small nuclei located immediately beneath the cerebral cortex of the medial anterior pole of each temporal lobe. It has abundant bidirectional connections with the hypothalamus as well as with other areas of the limbic system. The amygdala is understood to be a behavioral awareness area that operates at a semiconscious level. It also appears to project into the limbic system one’s current status in relation to both surroundings and thoughts. The most important function of the amygdala is to make the person’s behavioral response appropriate for each occasion… or not, as the case may be.

What specific stress behaviors are directly regulated by the amygdala? We can only infer, as the Maker did not provide a user manual, through observing what happens when the amygdala is accidentally or intentionally removed. Take the jump to find out.

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