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Endogenous opiate peptides can regulate neuroendocrine and circulatory responses to behavioral stress and may be important in the pathogenic effects of sympathoadrenal reactivity. We tested this hypothesis by examining the effect of the opiate antagonist naloxone on blood pressure responses to behavioral stress in young adults with high, medium, or low casual blood pressures. Naloxone increased mean arterial pressure responses to stress in subjects with low casual pressure, but had no significant effect on responses in subjects with high casual pressure. These results suggest opioidergic inhibition of sympathetic nervous system responses may be deficient in persons at risk for essential hypertension.

Eleven patients with Raynaud's syndrome accompanied by monospecific IgG ANA, nine patients with Raynaud's syndrome in the absence of ANA, and nine normal volunteers were exposed to an ambient cold challenge during which time venous blood was continuously sampled. ANA negative patients were shown to have significantly higher levels of cortisol during a cold challenge than either ANA positive patients or normal controls, and exhibited significantly lower levels of plasma norepinephrine compared with normal controls. ANA positive patients did not differ significantly from normals in their neuroendocrine response to cold. It is suggested that the high plasma cortisol found in Raynaud's syndrome in the absence of ANA may be responsible for the vasospasticity in this group of patients.

Studies dealing with the application of frontalis EMG feedback to the treatment of a variety of disorders are reveiwed. Successful applications of frontalis EMG feedback training have been reported in the treatment of muscle contraction headaches, asthma, essential hypertension, insomnia, chronic anxiety, phobias, and cerebral palsy. While available evidence does suggest that frontalis EMG feedback training may be helpful in the treatment of these disorders, these effects are equivalent but not superior to those that can be obtained using more conventional and less costly treatment techniques such as relaxation training. In addition, there appears to be a lack of clear rationale for the use of frontalis as a training site in treatment of these disorders. It is concluded that claims made about the clinical advantages of frontalis EMG biofeedback as compared to other methods of relaxation are not scientifically justified.

Prazosin and Autogenic Training had an additive effect in attenuating vasomotor tone during an ambient cold challenge in patients with Raynaud's phenomenon. The combination of these two treatments significantly elevated finger temperature during a 16 deg C ambient exposure, while neither treatment alone was found to produce this effect. This suggests that Autogenic Training and prazosin had an additive effect on reducing peripheral vasomotor activity.

Endogenous opioid regulation of blood pressure is altered during stress in young adults at risk for hypertension. We studied the effects of the opioid antagonist naloxone on the secretion of corticotropin and beta-endorphin during psychological stress in young adults with mildly elevated casual arterial pressures. Naloxone-induced secretion of both corticotropin and beta-endorphin was significantly diminished in persons at enhanced risk for hypertension compared with the low blood pressure control group. Results suggest that opioidergic inhibition of anterior pituitary function is altered in hypertension development.

Many investigators have begun to speculate that the sympathetic nervous system is involved in the pathophysiology of type II (noninsulin-dependent) diabetes mellitus (1–4). Recalling the early observations of Claude Bernard, who found that hyperglycemia could be produced in normal rabbits by lesioning the area of the hypothalamus, several groups have noted that hyperglycemia can be produced by chemical stimulation of the brain with morphine as well as with a variety of endogenous neuropeptides and can be abolished by bilateral adrenalectomy (1,5). Similarly, hyperglycemia has been shown to result from slow intravenous infusion of epinephrine (6) as well as from certain forms of stress that produce prolonged sympathetic discharge (7).

The obese (C57BL/6J ob/ob) mouse is a commonly used animal model of non-insulin-dependent diabetes mellitus. Recent experiments have shown that stress hyperglycemia can be classically conditioned in the obese but not in the lean mouse. In the present study, classical conditioning of insulin secretion was attempted in C57BL/6J obese and lean animals. For 21 days, obese and lean mice were exposed to a conditioned olfactory stimulus prior to and during eating. On the 22nd day, blood was sampled for all animals following presentation of the conditioned stimulus; testing was repeated 2 weeks later following an additional 4 days of conditioning. Results indicated an effect of conditioning, with significantly greater plasma insulin for trained than for untrained obese mice. That insulin secretion can be more easily conditioned in the obese mouse suggests that a cholinergic mechanism may be involved in the hyperinsulinemia characteristic of this animal.

The response of 111 chronic low back pain patients to a comprehensive behavioral treatment program emphasizing relaxation procedures is examined. Over the course of treatment, significant reductions were obtained on measures of subjective tension, EMG activity, and pain. Many patients also decreased their intake of analgesic/narcotic agents and reported an increase in activity level. In order to examine individual differences in pain relief, the 28 patients who had the greatest decreases in pain were compared to those who had the least decreases in pain. Patients who had the best outcome in terms of pain relief were significantly more likely to show improvements in other outcome measures. In addition, these patients rated their pain initially as more severe, had continuous pain for fewer years, and were less likely to be on disability or to have had multiple surgical procedures. These results are discussed in the light of recent data from other behavioral treatment studies with chronic low back pain patients and implications for behavioral assessment and treatment are discussed.

The obese (C57BL/6J ob/ob) mouse is a commonly used animal model of non-insulin-dependent diabetes mellitus. It has recently been demonstrated that this mouse is not consistently hyperglycemic, however, unless it is subjected to environmental stress. In the present study, hyperglycemia in obese mice was induced by classical conditioning. Obese diabetic mice and lean control animals were exposed to shaking stress. All animals developed hyperglycemia in response to shaking. To demonstrate classical conditioning, some obese and lean animals were exposed to a metronome prior to and during the shaking. Other animals were exposed to the metronome and shaking in a noncontingent fashion and one group of animals was exposed to the metronome without any exposure to shaking. All animals received seven exposures to one of the three above conditions over a 3-day period. On the 4th day all animals were exposed to the metronome alone, following which blood samples were drawn. Classical conditioning of stress hyperglycemia was demonstrated in obese, but not in lean, mice.

Thirty borderline essential hypertensives were randomly assigned to a portable constant-cuff blood pressure feedback technique or meditation-relaxation. Each technique was taught in the laboratory, then practiced twice daily at home for four weeks. Subjects mailed daily records of their progress. Seven feedback and ten meditation-relaxation subjects completed the program. Both techniques produced significant systolic and diastolic reductions within practice sessions and diastolic reductions over weeks of training. Neither technique improved reductions nor reduced initial systolic pressure levels over the four weeks. Differences between biofeedback and meditation-relaxation in within-session pressure reductions were not significant.

The genetically obese mouse (C57BL/6J ob/ob) is a commonly used model of non-insulin-dependent diabetes mellitus. However, our studies demonstrate that, while the animal is significantly hyperinsulinemic, it in fact does not show consistent hyperglycemia in the resting state. During stress, both obese animals and their lean littermates become hyperglycemie, but the magnitude of the hyperglycemia is exaggerated in the obese mice. Obese animals also show an exaggerated plasma glucose increase in response to epinephrine injection. This increase in plasma glucose is accompanied by a decrease in plasma insulin in response to both stress and epinephrine. Our findings suggest that environmental stimuli influence the expression of diabetes in the C57BL/6J obese mouse and therefore must be considered in studies of this animal model of diabetes.

This volume is the result of a NATO Symposium on Behavioral Medicine focusing on behavioral treatment of disease. It was part of the NATO Human Factors Conference and Symposia Program of 1981. Eighty-four scientists from ten NATO countries participated. This was the first major international meeting specifically devoted to behavioral treatment of disease. The meeting was intended to summarize the basic scientific and technical knowledge of the area. It more than achieved its goal.

We have shown that the C57BL/6J ob/ob (obese) mouse, a commonly used model of type II diabetes mellitus, is not in fact consistently hyperglycemic except when exposed to environmental stress. In an attempt to modify stress hyperglycemia in this animal, we administered either a 5 mg/kg dose of the benzodiazepine alprazolam or vehicle (propylene glycol) intraperitoneally to both obese mice and their lean littermates prior to a rest and a stress period. Alprazolam modified the hyperglycemic effect of stress only in the obese mice. Alprazolam significantly reduced plasma corticosterone in obese animals at rest and following stress. In addition, alprazolam significantly increased plasma insulin in all animals at rest and following stress. These data suggest a possible role for benzodiazepines in the modification of stress hyperglycemia in type II diabetes mellitus.

In 1862 Maurice Raynaud published his now famous thesis in which he first described the syndrome today known as Raynaud’s disease. Three interrelated phenomena were considered part of his new diagnostic category: local syncope or sudden blanching and numbness of the digits; cyanosis, during which time the pallor previously observed evolves into a blue color characteristic of deoxygenated tissue; and reactive hyperemia, characterized by the spread of red oxygenated blood through the upper layers of the epidermis. This last phase is often accompanied by burning and tingling and lasts until the skin returns to its normal pink color. In severe cases, patients experience chronic vasoconstriction or such frequent episodes of cyanosis that gangrene or small nutritive lesions and ulcerations often appear at the distal end of the digits. While vasospasms are usually confined to the digits of the hands and feet, they can occasionally appear on parts of the face as well. Cold stimulation is the most reliable eliciting stimulus, although emotional stress has also been reported to produce these attacks (Spittell, 1972). This is so because the mechanism of peripheral vasoconstriction is mediated by the sympathetic nervous system. Severe manifestations of this condition are not common, but Lewis (1949) has estimated that it affects approximately 20% of most young people in its mildest forms. Clinical Raynaud’s disease is found to occur five times more often in women than in men, the time of onset occurring in the first and second decades of life. When this syndrome results from an identifiable pathological process, it is known as Raynaud’s phenomenon.

Twelve patients with non-insulin-dependent diabetes mellitus were hospitalized on a clinical research ward under identical conditions. A 3-h glucose tolerance test and an intravenous insulin tolerance test were performed on each patient. Half of the patients werethen given 5 days of progressive relaxation training after which all patients were retested while treated patients practiced relaxation. Relaxation was found to significantly improve glucose tolerance without affecting insulin sensitivity or glucosestimulated insulinsecretory activity.

We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high–fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of >240 mg/dl and blood insulin levels of >150 μU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Futhermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.

Recent advances in behavioral psychology have disproved the notion that autonomic responses are involuntary. New techniques based on operant conditioning have shown that when given the proper feedback and motivation, animal and human subjects can learn to control a wide variety of physiological responses. These new data suggest a behavioral alternative to present theories of psychosomatic medicine which rely heavily on psychodynamic formulations for their therapeutic technique. Such a behavioral approach would, like other forms of behavior modification, treat the symptom directly through the use of learning techniques based on operant conditioning. Experimental and clinical examples of these techniques as applied to problems of muscle tension and blood pressure are presented.

Fourteen female subjects suffering from idiopathic Raynaud's Disease were trained during 6 laboratory sessions to raise skin temperature. All subjects were given autogenic instructions and half the subjects were given skin temperature feedback from the middle digit of the dominant hand. Autogenic instructions were found to produce small but reliable increases in skin temperature regardless of whether or not feedback was provided. Following the autogenic instructions all subjects showed decreases in skin temperature. However, these decreases were greater for subjects not receiving feedback than for those receiving feedback. Theoretical implications of these data are discussed.

Raynaud’s Disease is a syndrome of disrupted peripheral bloodflow first described by Maurice Raynaud in 1862. A triphasic color change, usually exhibited in the digits of the hands or feet, is the hallmark of the disorder: sudden blanching and numbness of the affected part, due to localized arteriolar constriction; cyanosis, in which the pallor previously observed evolves into a blue color, characteristic of deoxygenated tissue and attributed to retarded blood flow in dilated capillaries and venules; and reactive hyperemia, characterized by the spread of red oxygenated blood through the upper level of the epidermis. This last phase is often accompanied by burning and tingling and lasts until the skin returns to its normal pink color. Only a minority of patients actually exhibit the classic triphasic color change, however, isolated pallor or cyanosis are much more likely (Porter, Rivers, Anders, & Baur, 1981). Typically, ischemia starts in the fingertips and progresses proximally to a variable degree, but rarely involves the palm. Occasionally, the earlobes, cheeks, and tip of the nose may also be affected (Hoffman, 1980). Attacks may last from minutes to hours and usually involve a local sensation of coldness, a loss of manual dexterity and considerable pain that can result in the interruption of routine activity. In severe cases, patients experience chronic vasoconstriction or such frequent episodes of cyanosis that gangrene or small nutritive lesions and ulcerations can appear at the distal end of the digits. Although cold stimulation is the most reliable eliciting stimulus, emotional stress has also been reported to produce these attacks (e.g., Mittlemann & Wolff, 1939).

This chapter concerns itself with the application of learning techniques to the remediation of disease. Although the idea of teaching people to control their physiology can be traced back to antiquity, learned control of visceral responses and other involuntary functions has only recently come under systematic investigation by psychologists. This research has developed techniques that, for the first time, have enabled therapists to place the physiological activity of the body under the control of environmental contingencies, in much the same way as has been done with other types of behavior. In essence, it now seems feasible to extend the scope of behavior modification into the domain of medicine.

Electromyographic biofeedback is becoming widely used to help patients regain voluntary control of specific muscles affected by neuromuscular disorders. Electromyographic feedback training has been employed in the rehabilitation of patients affected by poliomyelitis, cerebrovascular accident, torticollis, nerve injury, temporomandibular joint syndrome, bruxism, and other disorders. While EMG biofeedback appears to be a promising treatment technique, the research literature on its effectiveness consists mainly of uncontrolled case reports and clinical trials. It is concluded that new studies with more sophisticated designs and more careful control are needed to demonstrate that EMG biofeedback makes a unique contribution to the treatment of neuromuscular disorders. Research is needed to identify relevant patient characteristics predictive of success, specify appropriate muscle groups for the treatment of particular disorders, determine how feedback can be most efficiently combined with more conventional techniques in achieving a therapeutic effect, and establish meaningful criteria of success in the treatment of neuromuscular disorders.

This study examined the efficacy of a simple autogenic and biofeedback treatment package in the management of Raynaud's Phenomenon secondary to diagnosed collagen vascular disease. The patient, diagnosed as suffering from mixed connective tissue disease, had an average of 6.3 vasospastic attacks per day during a 2 week baseline period. The frequency of daily attacks dropped to 4.2 after 10 weeks and 2.5 attacks after 1 yr of training. In addition, the patient displayed a gradual improvement in the ability to maintain digitial skin temperature in the presence of ambient cold stress.

Because essential hypertension affects about 10 percent of the general population, behavioral manipulation of blood pressure has received much attention as a possible clinical tool (Shapiro & Surwit, 1976). Over the past six years, a number of different behavioral techniques have been clinically applied to the control of hypertension. The main purpose of this study was to compare the efficacy of three such methods in the treatment of essential hypertension.

The purpose of this study was to assess to what degree learned control of digital temperature and vasospastic attacks can be retained by Raynaud's patients over a full year period. Subjects were 19 patients suffering from diagnosed idiopathic Raynaud's disease who had undergone behavioral training. These patients had been trained to increase digital temperature using either autogenic training, biofeedback, or a combination of autogenic training and temperature biofeedback. Results indicated that the mean number of vasospastic attacks per day occurring 1 year after training was approximately equal to the number occurring at the end of the initial training (1.2-1.3 per day). Patient satisfaction with the treatment program was above average (3.5 on a 5-point scale). The patients' ability to maintain digital temperature during the cold stress challenge was impaired, however. At 1-year follow-up, digital temperature readings taken in the laboratory were identical to baseline levels.

Interest in the biology of adipose tissue has undergone a revival in recent years with the discovery of a host of genes that contribute to the regulation of satiety and metabolic rate. The catecholamines have long been known to be key modulators of adipose tissue lipolysis and the hydrolysis of triglyceride energy stores. However, more recent efforts to understand the role of Individual adrenergic receptor subtypes expressed in adipocytes and their signal transduction pathways have revealed a complexity not previously appreciated. Combined with this interest in the modulation of adipocyte metabolism is a renewed focus upon brown adipose tissue and the mechanisms of whole body thermogenesis in general. The discovery of novel homologs of the brown fat uncoupling protein (UCP) such as UCP2 and UCP3 has provoked intensive study of these mitochondrial proteins and the role that they play in fuel metabolism. The story of the novel UCPs has proven to be intriguing and still incompletely understood. Here, we review the status of adipose tissue from inert storage depot to endocrine organ, Interesting signal transduction pathways triggered by β-adrenergic receptors in adipocytes, the potential of these receptors for discriminating and coordinated metabolic regulation, and current views on the role of UCP2 and UCP3 based on physiological studies and gene knockout models.

Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased by high fat feeding in adipose tissue of the A/J strain of mice, which is resistant to the development of dietary obesity. More recently, a third UCP (UCP3) was identified, which is expressed largely in skeletal muscle and brown adipose tissue. The UCP2 and UCP3 genes are located adjacent to one another on mouse chromosome 7. Thus, the roles of these UCPs in both metabolic efficiency and the linkage to obesity and diabetes syndromes is unclear. For this reason, we examined the expression of UCP2 and UCP3 in white adipose tissue and interscapular brown adipose tissue and in gastrocnemius/soleus muscle preparations from the obesity-resistant A/J and C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6J (B6) mouse strain. In both KsJ and A/J mice, UCP2 expression in white fat was increased ≈2-fold in response to 2 weeks of a high fat diet, but there was no effect of diet on UCP2 levels in B6 mice. In skeletal muscle and in brown fat, neither UCP2 nor UCP3 expression was affected by diet in A/J, B6, or KsJ mice. However, in brown fat, we observed a 2–3-fold increase in the expression of UCP1 in response to dietary fat challenge, which may be related to diet-induced elevations in plasma leptin levels. Together, these results indicate that the consumption of a high fat diet selectively regulates UCP2 expression in white fat and UCP1 expression in brown fat and that resistance to obesity is correlated with this early, selective induction of UCP1 and UCP2 and is not associated with changes in expression of UCP3.

Amygdaloid lesioned rats were compared to cortically lesioned and normal rats in their level of shock-induced fighting behavior. The resultant fighting scores, as rated on a four point scale, showed no significant difference in aggressive behavior on the part of the amygdalectomized group as compared to the cortical and normal control groups. Theoretical explanations of the results are proposed.

• Twenty-four patients classified as having Raynaud's disease or Raynaud's phenomenon were given bilateral brachial artery injections of reserpine or saline in a double-blind fashion. In the six weeks following injection, there was no indication that reserpine produced clinical improvement or changed vasomotor reactivity in the treated patients. However, intra-arterial reserpine did produce systemic cardiovascular effects lasting up to six weeks. It is concluded that intra-arterial reserpine as used in this study is an ineffective treatment for Raynaud's disease or Raynaud's phenomenon and may have significant adverse effects. (Arch Dermatol1983;119:733-735)

Nineteen patients with Raynaud's phenomenon in conjunction with progressive systemic sclerosis were given either prazosin hydrochloride (1 mg orally three times a day) or a placebo for eight weeks, after which the treatment procedure was reversed for four weeks. Prazosin was shown to be effective in reducing both the frequency and the severity of vasospasm reported by the patients.