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Psychosomatic Medicine:
Dealing with Stress and Pain
Psychological factors may exacerbate or
even trigger medical disorders
• Poor behavioral choices (e.g., diet, exercise,
smoking, excess alcohol)
• Personality factors (Type A behavior)
• Mental disorders (e.g., depression) can
contribute to other diseases
• Stressful events or circumstances can
precipitate or exacerbate diseases
Type A behavior: Obsessive-compulsive, fear loss of control, excessively intrinsically-originating pressure to get
things done, competitiveness, sometimes hostile (Type A hostility is statistically associated with coronary disease)
PSYCHONEUROIMMUNOLOGY
The concept of a stress response: Physical or psychological stress alters the body's
neuroendocrine systems. Responses are attempts to successfully cope with stress. When
stress is severe or chronic, the altered physiology can cause or exacerbate health
problems.
Holmes life stress scale: statistical association between stress and numerous illnesses.
Negative events are more detrimental than positive ones.
Selye's general adaptation syndrome: Endocrine response to acute and chronic stress.
Stress and disease: immune system cells both synthesize and respond to ACTH and betaendorphins.
Ader: Conditioned immunosuppression in rodents; conditioned immunoactivation.
Pairing exposure to immunoactivators or immunosuppressors with smells.
Chronic stress reduces a variety of immune indices in humans. (Glaser & Kiecolt-Glaser)
Chronic stress decreases resistance to infectious diseases in mice (Ader).
80% of Pts with a
total of > 300 in a
year became Ill during
the subsequent year
Thomas Holmes
Social Readjustment
Rating Scale
Journal of Psychosomatic
Research 11:216, 1967
PSYCHONEUROIMMUNOLOGY
The concept of a stress response: Physical or psychological stress alters the body's
neuroendocrine systems. Responses are attempts to successfully cope with stress. When
stress is severe or chronic, the altered physiology can cause or exacerbate health
problems.
Holmes life stress scale: statistical association between stress and numerous illnesses.
Negative events are more detrimental than positive ones.
Selye's general adaptation syndrome: Endocrine response to acute and chronic stress.
Stress and disease: immune system cells both synthesize and respond to ACTH and betaendorphins.
Ader: Conditioned immunosuppression in rodents; conditioned immunoactivation.
Pairing exposure to immunoactivators or immunosuppressors with smells.
Chronic stress reduces a variety of immune indices in humans. (Glaser & Kiecolt-Glaser)
Chronic stress decreases resistance to infectious diseases in mice (Ader).
Prolonged exposure to stage of resistance is chronic stress
Release of glucocorticoids from the adrenal
Cortex is an important part of stress response
Minutes to hours
Hours to indefinite
H. Selye: General Adaptation Syndrome:
Stress reaction has 3 stages, Alarm, Resistance and
Exhaustion. Stress disorders represent reaction to chronic
involvement in stage of resistance, "wearing down."
Selye:
*
Eustress
(+)
e.g., physical exercise
*
Distress
(-)
e.g., environmental pressures
Lazarus emphasized coping vs. vulnerability as a key
dimension as to whether stress resulted in stress disorders.
Stress
v
Neural Activation - Hypothalamus
v
Secretion of Corticotrophin Releasing Factor (CRF)
v
Pituitary Release of Adrenocorticotrophic Hormone
(ACTH)
v
Adrenal Release of Glucocorticoids
v
Metabolic, Immunological, Psychological Responses
Stress Response
Central
Nervous System
Hypothalamus
releases CRF
(Corticotrophin
Releasing Factor)
Activation of
Norepinephrine
Dopamine, Serotonin
Neurons
Pituitary Discharges
other releasing
Factors
Hormones
Pituitary
releases ACTH
(Adrenocorticotrophic
Hormone)
Spinal Cord
Neuronal
Monoaminergic
Pathways
Various
Effects on Brain,
Other Organs
Immune System
Stimulates
Adrenal Cortex
to release
Corticosteroids
Stimulates
Adrenal Medulla
to release
Catecholamines
Prepare the Body for Resistance to Stress:
Increased sweating Gluconeogenesis Pupil dilation
Reduced inflammatory response Increased heart rate
Reduce immune response Increased respiratory rate
Hyperinsulinemia
Increased gastric secretion
Decreased gastrointestinal mobility
Increased blood pressure Lysis of lymphoid tissue
PSYCHONEUROIMMUNOLOGY
The concept of a stress response: Physical or psychological stress alters the body's
neuroendocrine systems. Responses are attempts to successfully cope with stress. When
stress is severe or chronic, the altered physiology can cause or exacerbate health
problems.
Holmes life stress scale: statistical association between stress and numerous illnesses.
Negative events are more detrimental than positive ones.
Selye's general adaptation syndrome: Endocrine response to acute and chronic stress.
Stress and disease: immune system cells both synthesize and respond to ACTH and betaendorphins.
Ader: Conditioned immunosuppression in rodents; conditioned immunoactivation.
Pairing exposure to immunoactivators or immunosuppressors with smells.
Chronic stress reduces a variety of immune indices in humans. (Glaser & Kiecolt-Glaser)
Chronic stress decreases resistance to infectious diseases in mice (Ader).
Glucocorticoids from adrenal cortex
Gluconeogenesis (from protein)
Suppressed inflammation
Immunosuppression
decreased lymphocyte response
impaired natural killer cell function
Feedback to brain (esp Hippocampus)
STRESS AND DISEASE - Ia
Peptic Ulcers:
•
For years there was an established relationship
between peptic ulcers (and other GI irritative diseases) and
psychological stress.
•
Marshall and Warren “Unidentified curved bacilli in
the stomach of pts with gastric and peptic ulceration” (Lancet,
1984)
•
Very tight causal relation between Helicobacter pylori
and peptic ulcer and other irritative GI diseases.
•
Diagnosis of infection (serology, IGG for H.p.; or
endoscopy-biopsy), treat with antibiotics (tetracycline,
metronidazole), is eradicating H. pylori infection in much of
US population
So What Happened to the Relationship to Stress?
STRESS AND DISEASE - Ib
Evidence for a Relationship Between Stress and Ulcers:
•
Gastric fluids increase acidity in response to anger, hostility,
resentment, guilt, frustration.
•
Stressful situations (surgery, school exams) increase basal gastric
acid secretion.
•
Alleviation of stress can reverse peptic ulcer condition.
•
Animals exposed to stress develop stomach ulcers.
•
Ulcer occurs in the absence of H. pylori infection.
•
Most people still have H. pylori infection and do not have ulcers.
•
Ulcer patients more likely to exhibit excess stress (Levenstein &
Veylan, J. Clin. Gastroenterol., 1995).
•
Psychological stress impedes ulcer healing.
•
Other factors also important: sex (choose female), blood type (avoid
O), other genetics, cigarettes, coffee, alcohol consumption patterns,
possibly diet. These are not correlated with presence or degree of H.
pylori infection.
•
A “Psychosomatic” etiology is often preferentially discarded as
soon as a “biological” explanation becomes available.
STRESS AND DISEASE - Ic
Aside from Impaired Treatment of Pts and Widespread
Overprescription of Antibiotics, are there Costs? On the
Horizon:
•
Absence of H. pylori infection may be linked to
gastroesophogeal reflux disease (“acid reflux”; Labenz
et al., Gastroenterology, 1997)
•
Reflux disease increases risk for gastric adenocarcinoma,
a serious form of malignancy, which has recently also
been linked by co-occurrence to absence of H. pylori
infection.
•
H. pylori infection is dropping, especially among SES
levels with good medical care.
•
Stay tuned. And don’t throw out good data just because
something more “biological” comes along. Consider the
whole patient, both in theory and in practice.
STRESS AND DISEASE Iia
Coronary Artery Disease (Leading US cause of death; 1,250,000 heart
attacks/year):
• Type A behavior? (Time urgency, competitive achievement orientation, anger
hostility). Controversial, particularly in details, hostility may be most
predictive of CAD.
• Stress can increase serum cholesterol levels.
Sudden Cardiac Death:
• Heart arrhythmias may be associated with chronic stress (animal and human
studies)
• Clear evidence for stress as cause or contributing factor in many human
clinical cases
Learned Helplessness (Seligman):
• Controllable vs. uncontrollable life events; uncontrollable events lead to
feelings of helplessness
• Sense of personal control of one’s life leads to greater self-efficacy,
“hardiness”
• May be a model for depression
STRESS AND DISEASE IIb
Hypertension (incidence: 25-38% of adults); major risk factor for cardiac and
brain disorders:
•
Chronic stress leads to hypertension in animal studies
•
Human studies suggest greater tendency towards hypertension with
stress.
Stressful occupations: Air traffic controllers have exceptionally high
prevalence of hypertension
Cancer:
•
Rats subjected to stress less likely to reject tumor implants
•
Women who respond poorly to stress: cervical cancer incidence higher;
increased incidence of malignacy in breast biopsies
•
Depressed mood linked to increased cancer risk
STRESS AND THE IMMUNE SYSTEM
Stress and disease: immune system cells both
synthesize and respond to ACTH and beta-endorphins.
Ader: Conditioned immunosuppression in rodents;
conditioned immunoactivation. Pairing exposure to
immunoactivators or immunosuppressors with smells.
Stress Impairs Resistance to Infection in Laboratory
Animals
(Ader)
STRESS AND THE IMMUNE SYSTEM
Evidence that Psychological Stess Affects Human Immune Function
(Kiecolt-Glaser & Glaser, 1987)
*
*
*
*
*
*
*
Men whose wives had died of breast cancer had decreased
immune function
Marital disruption is associated with increased morbidity and
mortality
Divorced people more likely to die from pneumonia than married
people
Women who are separated have 30% more appointments for
physical illness
Patients with mental illness have greater numbers of physical
illnesses
Medical students have reduced immune function (Natural Killer
Cell activity) during final exams
The Holmes life stress scale receives biological validation
STRESS AND PSYCHIATRIC ILLNESS
*
Social stressors often associated with depression
*
Other medical illnesses increase probability of
psychiatric disorders by about 1/3
*
Posttraumatic stress disorder: often see loss of affect,
withdrawal, other signs of depression, some violent
hostile behavior patterns, etc.
*
Kindling theory of depression (like kindled seizures)
*
Up to four-fold increase in incidence of psychiatric
symptoms in people with high stress levels and poor
coping skills vs. people with low stress levels, good
coping skills
STRESS AND THE BRAIN
• Aging memory disorders - non-Alzheimer or other dementias.
Associated with hippocampal neuron loss
• Animal model: Chronic stress or glucocorticoid exposure
• Stress induces:
– Neuron loss in hippocampus (esp. region CA1) (Sapolsky)
– Adrenalectomy induces hippocampal granule cell loss
(Sloviter)
– Individual stress history, indicated by adrenal weight, predicts
hippocampal pyramidal cell loss with aging (Landfield)
STRESS AND THE BRAIN (Continued)
• Mechanism (?) (Sapolsky)
– Glucocorticoids disrupt hippocampal glucose utilization. This
leaves neurons vulnerable to insults.
– Glucocorticoid administration sensitizes the hippocampus to
epilepsy or hypoxia
– Glucose supplements protect the hippocampus
– Likewise, monkeys that died from ulceration had more
hippocampal neuron loss than those that did not.
• Early Handling protects against stress-induced neuron loss
BOTTOM LINE: STRESS AFFECTS THE BRAIN, AND THE
WRONG KIND OF STRESS AFFECTS IT NEGATIVELY. THE
ANSWERS ARE FAR FROM ALL IN, AND AS A PHYSICIAN,
CONTINUING TO EDUCATE YOURSELF ABOUT THIS WILL
BE IMPORTANT.
NEW TOPIC: PAIN
ACUTE PERIPHERAL PAIN (You will get again in Neuro course)
Epidermal Pain: c-fiber activation by intense physical stimulation
Injurious tissue damage --> bradykinin (peptide), which in turn activates
c-fibers
c-fibers: small, unmyelinated somatosensory fibers that innervate
epidermis, striated muscle, joints, etc.
*
most senstive to local anesthetics
*
interact with other sensory input to amplify pain sensation
Opiate systems in spinal cord react to diminish this type of pain within a
few minutes.
This system subserves acute pain.
ACUTE PERIPHERAL PAIN
Anti-opiates such as naloxone may increase pain, revealing
effects of the body’s opiate systems.
Placebo (“sugar pill”) administration may sometimes cause
activation of opiate systems if subjects believe the pills are
painkillers. Naloxone-sensitive pain reduction. Psychological
activation of endogenous opiate systems.
However, acute pain can modify central systems on a longer
term basis. It is now commonly recommended that both
peripheral “local” anesthetization and global anesthetic
administration be used in conjunction with pain-inducing
surgical procedures. Repetitious activation of C fibers builds
up the electrical response of neurons to which they project in
the spinal cord. This resembles LTP, a process thought to be
involved in memory.
According to S. Siegel, an addict can take a dosage of heroin that would
kill a person not used to it. But in fact, if the dosage is administered to the
addict when he is unaware of it, it can kill the addict as well.
Behavioral tolerance (to be described if time allows) suggests that
conditioning affects the response to drugs.
A rat can tolerate a larger dosage of an opiate if it is used to getting the
opiate in a particular setting.
Alternating injections, water and alcohol. Alcohol reduces body
temperature. If all alcohol injections occur in one room and water
injections in another, animals “defend” body temperature against alcohol.
Addictions can also be dependent on context. Leaving an environment
can leave drug addictions behind (e.g., Vietnam veterans). Reinstating
environmental conditions can cause feelings of withdrawal.
S. Siegel et al., Heroin overdose death: contribution of drug-associated environmental cues. Science, 216: 436-7, 1982
CHRONIC PAIN
Chronic Pain: Basis is often much less clear. Incidence: more
than 40% of the population will experience pain at some time in
their lives.
Chronic pain is not merely persistent acute pain. It may occur in
the absence of obvious peripheral or visceral pathology.
All pain has both sensory and affective-evaluative components.
Focusing exclusively on either of these alone is equally
misguided.
With chronic pain there is not a linear relationship between
nociception and pain experience. In chronic pain syndromes,
there are qualitative differences in the affective-evaluative
perception of pain.
Prevalence of chronic pain increases with age
Sources of Chronic Pain
Chronic Benign Pain: Any pain resulting from nonmalignant causes that
is not allieviated by appropriate medical, pharmacotherapy, or surgical
treatment.
Example: Fibromyalgia, widespread aching, local tenderness, absence of
laboratory evidence of inflammation.
American College of Rheumatology defines as involving 3 or more
segments of the body and at least 11 of 18 “tender points.” (e.g.,
trapezius, rib junctions, buttocks, knees)
Steroids and NSAIDS have no more effect than placebo. (Placebos
benefit 50% of patients, at least short-term.) Ketamine (NMDA receptor
antagonist) appears to be effective in 50% of patients.
Some think fibromyalgia is one extreme on a continuum of widespread
chronic pain syndromes. Higher incidence in females.
Opiates remain the most effective medications for managing chronic
pain.
Behavioral Approaches to Chronic Pain Management
It was historically thought that chronic pain patients exaggerated trivial
pain problems--not made of “the right stuff.” This is not therapeutically
helpful. Goal is restoration of functional life.
Chronic pain can have secondary consequences: depressive illness,
marital discord, job problems social withdrawal, sleep disorders.
Biofeedback therapies combine feedback from detectors such as muscle
EMG electrodes with techniques such as muscle relaxation to affect muscle
function.
Biofeedback can be effective for muscle contraction headaches, for
symptoms of chronic stress such as anxiety, and for blood pressure
disorders such as hypertension.
Controlling pain behavior through operant conditioning and other
behavioral approaches has also had success. The approach focuses upon
modifying pain-related behavior separately from the treatment of the pain
itself.
Exercise and conditioning (e.g. stretching) is a very important mitigator of
increased chronic pain with aging. Mild joint and limb pain is very common
in sedentary (inactive) aging people.
Gate Control theory of Pain (Melzack): the interpretation of sensation
as painful depends on the relative amounts of large fiber vs. small
fiber (c-fiber) activity. Propose stimulating large fibers. Works for
some pts, not all.
Chronic treatment with normally addictive drugs such as opiates is
not as addictive as expected if the withdrawal of the opiate
accompanies mitigation of the pain due to recovery or some other
form of treatment. The addictions are often context-dependent and, if
the context, chronic pain, goes away, the addiction may do likewise.
Pain increases in incidence in elderly. Physicians may dismiss as
“just a part of growing old.” This is age discrimination and not
appropriate. Physician should make every attempt to diagnose and
treat the pain.