Edith E. Bragdon

High stress responsivity predicts later blood pressure only in combination with positive family history and high life stress.

High cardiovascular responsivity to stressors has not consistently improved prediction of later blood pressure increases beyond the predictive effects of baseline pressure. Animal models suggest that genetic susceptibility to hypertension and frequent stress exposure are important modulating factors in stress-related hypertension. Thus in 103 men originally tested at age 18 to 22 years and reassessed 10 years later, interactive effects of genetic susceptibility (defined as 1 or more hypertensive parents) with high stress responsivity (defined as top 25% on the basis of blood pressure and cardiac responses during both reaction time and cold pressor tasks) were examined in relation to follow-up systolic and diastolic levels and to change in blood pressure status from normal (diastolic<80 mm Hg) to marginally elevated (diastolic 85 to 95 mm Hg). Men with the combination of high stress response and hypertensive parents demonstrated higher systolic (P<0.05) and diastolic levels (P<0.05) at follow-up, and they showed a 7-fold increase (7.5, 95% confidence intervals 2.3, 24.3; P<0.001) in relative risk of change in blood pressure status versus men with no family history and a 3-fold increase (3.8, confidence intervals 1.5, 9.6; P<0.004) versus less stress-responsive men who also had hypertensive parents. In 65 men who also provided ratings of daily stress, family historyxstress responsivityxdaily stress interactions were significant in predicting follow-up systolic and diastolic levels (P<0.006 and 0.03, respectively), with highest pressure levels seen when high life stress was reported by high stress responders and/or men with hypertensive parents. In conclusion, results suggest that stress responsivity as a long-term predictor is modulated by both genetic and environmental factors.

Group differences in pain modulation: pain-free women compared to pain-free men and to women with TMD

&NA; Previously reported differences in sensitivity to experimental pain stimuli between the sexes, as well as between temporomandibular disorder (TMD) patients and healthy control subjects, may be attributable in part to group differences in two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous opioid system. Twenty‐two pain‐free (PF) men, 20 PF women and 20 women with TMD underwent two testing sessions in which heat pain and ischemic arm pain threshold and tolerance were measured during both sessions, but followed relaxation during one session and laboratory stress tasks during the other. Blood pressure (BP) and plasma &bgr;‐endorphin (&bgr;E) concentration were measured during a baseline rest and during the stress or relaxation periods. PF mens threshold and tolerance for heat pain, but not for ischemic pain, exceeded that of PF womens during both sessions. PF women and TMD women did not differ in sensitivity to either pain modality; however, significantly lower ischemic pain threshold (IPTh) was linked to oral contraceptive use in PF women but not TMD patients. In the men alone, higher baseline systolic BP (SBP) was correlated with higher heat pain threshold on both days and heat pain tolerance on the stress day. Conversely, in TMD women, higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on both days; BP and pain sensitivity were not related in PF women. In men, but not in PF or TMD women, stress systolic and diastolic BP were positively correlated with heat pain threshold and tolerance and higher diastolic reactivity to stress were correlated with higher heat pain and IPTh and tolerance. On the stress day, higher baseline &bgr;E level was strongly associated with higher IPTol in PF women but marginally associated with lower IPTol in TMD women. Thus, it appears that a BP‐related analgesic mechanism (probably baroreceptor‐mediated) predominates in PF men, while an endogenous opioid mechanism predominates in PF women. Stress enhances the expression of these central mechanisms. Female TMDs appear unable to effectively engage normal pain‐inhibitory systems; opioid receptor desensitization and/or downregulation are probably implicated, because TMDs production of &bgr;E appears normal.

Relation between systemic hypertension and pain perception.

To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain-controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system.

Adrenergic Dysregulation and Pain With and Without Acute Beta-blockade in Women with Fibromyalgia and Temporomandibular Disorder

UNLABELLEDnIn patients with fibromyalgia syndrome (FMS) and temporomandibular disorder (TMD), stress and pain may chronically enhance sympathetic activity, altering cardiovascular responses and worsening pain. This study examined cardiovascular, epinephrine (EPI), norepinephrine (NE), cortisol and clinical pain responses in 54 female patients with these disorders and 34 controls. In a subsample of 10 FMS, 10 TMD patients and 16 controls, using a counterbalanced, double-blind, crossover design, the same responses were assessed after intravenous administration of low dose propranolol vs placebo. Testing included baseline, postural, speech and ischemic pain stressors. FMS patients showed lesser heart rate (HR) increases to posture challenge but greater blood pressure (BP) increases to postural and speech tasks than controls, as well as higher overall BP and greater total vascular resistance (TVR) than TMDs or controls. TMDs showed higher overall cardiac output and lower TVR than controls. Both FMS and TMD groups showed lower baseline NE than controls, and TMDs showed lower overall EPI and NE levels. Group differences in HR, EPI and NE were abolished after propranolol although BP, CO and TVR differences persisted. In both FMS and TMD, the number of painful body sites and ratings of total clinical pain obtained 4 times during each session were significantly lower after beta-blockade vs placebo.nnnPERSPECTIVEnThese findings support the hypothesis that both FMS and TMD may frequently involve dysregulation of beta-adrenergic activity that contributes to altered cardiovascular and catecholamine responses and to severity of clinical pain. Acute treatment with low-dose propranolol led to short-term improvement in all these domains.

Aging and pain perception in ischemic heart disease

Age is a recognized risk factor for coronary artery disease, but the relationship between age and silent ischemia is not well understood. We analyzed the data from 35 rest/stress radionuclide ventriculography examinations in patients with documented ischemic coronary artery disease who had experienced 1 mm ST segment depression accompanied by angina during exercise testing. An index of ischemic cardiac pain perception (PPI) was calculated by subtracting the time of onset of 1 mm ST segment depression from the time of onset of angina. The mean value of PPI was -97 +/- 311 seconds. PPI was significantly correlated with age (r = 0.37, p = 0.03). This suggests that as age increases, perception of pain during myocardial ischemic episodes becomes muted. This relationship remained significant when we controlled for the presence of medication and severity of disease (change in ejection fraction from rest to peak exercise). These findings suggest that age is an independent risk factor for a decreased perception of ischemic cardiac pain, and thus for silent myocardial ischemia.

Temporomandibular disorder and optimism: relationships to ischemic pain sensitivity and interleukin-6

&NA; The current study examined patients with temporomandibular disorders (TMD) (n=20) and pain‐free controls (n=28) under stress and relaxation conditions. Interleukin‐6 (IL‐6), norepinephrine and epinephrine (NE and E) were measured both before and during each of two conditions: a non‐stressful relaxation period and a speech stressor. Ischemic pain sensitivity was also assessed after each of these conditions. Optimism (Life Orientation Test (LOT)), which has been associated with better outcomes in relationship to health and disease, was also evaluated in relationship to ischemic pain tolerance and unpleasantness ratings as well as to IL‐6 levels under the two conditions. Regression analysis determined the unique contribution of each predictor and the interaction between Optimism and Group (TMD versus controls) after controlling for gender and blood pressure. During stress, IL‐6 levels appeared to parallel NE with only controls displaying significant increases. After controlling for depressed mood, TMD patients as a whole showed a significantly blunted response in IL‐6 levels produced during stress as compared to controls (&bgr;=0.31*). Although TMD subjects as a whole did not show the expected greater pain sensitivity to the ischemic task, those displaying a less optimistic style did exhibit lower pain tolerance times (&bgr;=−0.61*) and higher pain unpleasantness ratings (&bgr;=0.48*), compared with low optimism controls and high optimism TMD patients. Less optimistic TMD patients also had higher NE and IL‐6 levels during stress than other TMD patients, while optimism was unrelated to responses in controls (*P<0.05).

Beta-endorphin response to exercise and mental stress in patients with ischemic heart disease

UNLABELLEDnWe compared symptomatic, hemodynamic and opioid responses of heart disease patients to exercise testing and a stressful public speaking task. Plasma beta-endorphins were measured at rest and immediately post stress. Nineteen of 50 patients had angina during exercise; 31 had asymptomatic ischemia. No patient had angina during the speech, but two had ECG changes and 39% had radionuclide changes indicating ischemia. Patients with asymptomatic ischemia on exercise had a significantly greater beta-endorphin response than those with angina. Public speaking elicited a significantly larger beta-endorphin increase relative to change in double product (an index of stress) than did exercise.nnnCONCLUSIONSn(1) Patients with silent vs painful ischemia experience a greater beta-endorphin response to exercise. (2) beta-endorphin response to a speech stressor is greater than to exercise when controlled for an index of stress. (3) Increased beta-endorphin response to a speech stressor may partially explain the predominance of silent ischemia during psychological stress.

Myocardial ischemia during daily activities the importance of increased myocardial oxygen demand

The role of increased myocardial oxygen demand in the pathophysiology of myocardial ischemia occurring during daily activities was evaluated in 50 patients with coronary artery disease and exercise-induced ST segment depression. Each patient underwent ambulatory electrocardiographic (ECG) monitoring for ST segment shifts during normal daily activities and symptom-limited bicycle exercise testing with continuous ECG monitoring. All 50 patients had ST depression greater than or equal to 0.1 mV during exercise. A total of 241 episodes of ST depression were noted in the ambulatory setting in 31 patients; only 6% of these were accompanied by angina pectoris. Significant (0.1 mV) ST depression during ambulatory monitoring was preceded by a mean increase in heart rate of 27 +/- 12 beats/min. Patients with ischemia during daily activities developed ST depression earlier during exercise (7.9 +/- 4.4 vs. 14.2 +/- 6.4 min, p less than 0.001) and tended to have significant ECG changes at a lower exercise heart rate and rate-pressure product than did those without ST depression during ambulatory monitoring. In the 31 patients with ischemia during daily activities, the mean heart rate associated with ST depression in the ambulatory setting was closely correlated with the heart rate precipitating ECG changes during exercise testing (r = 0.74, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Depression and Type A behavior pattern in patients with coronary artery disease: Relationships to painful versus silent myocardial ischemia and β- endorphin responses during exercise

&NA; A sample of 45 patients with a history of coronary heart disease and documented myocardial ischemia during exercise testing were evaluated in an investigation of the possible relationships between psychological factors (depression and Type A behavior pattern), plasma beta‐endorphin response and pain experience during maximal exercise‐induced ischemia. Depression was assessed using the MMPI‐D subscale, while Type A was evaluated using the Structured Interview. All patients developed ischemia during exercise as defined by ST‐segment depression; however, only 18 patients reported anginal pain. Patients with high depression scores (MMPI‐D greater than or equal to 70; n = 13) showed lesser increases in plasma beta‐endorphin levels, tended more often to report anginal pain and rated pain as more severe during exercise than patients with low depression scores (MMPI‐D less than 60; n = 18). Hemodynamic responses and severity of ischemia (assessed by ejection fraction changes and wall‐motion abnormalities) did not differ between depression groups. Even after adjustment for group differences in exercise duration, depression was significantly associated with a lesser beta‐endorphin response in the sample as a whole and, among patients reporting angina, with earlier pain onset and greater pain duration and severity. In contrast, when Type A versus B/X subgroups were compared, no differences in pain experience, beta‐endorphin response or measures of ischemia were obtained. These findings suggest that in patients with ischemic heart disease, there may be a relationship between depression and anginal pain which may in part involve a blunted or absent beta‐endorphin response.

Stable Pessimistic Attributions Interact with Socioeconomic Status to Influence Blood Pressure and Vulnerability to Hypertension

We investigated the relationship of pessimistic attributional style (specifically, stable attributions for negative events) and socioeconomic status (SES) to cardiovascular and catecholamine profiles in a biracial sample of 37 postmenopausal women (aged 39-64 years) not taking hormone replacement therapy (HRT). Blood pressure (BP) variation in response to the demands of daily life was assessed by 24-hour ambulatory monitoring on a typical workday. Subjects were classified into groups by stable pessimistic attributions (high vs. low pessimism) and by SES (high vs. low). Significant SES x pessimism interactions were found. Low SES/high pessimism women demonstrated higher systolic BP (SBP) during the day, evening, and sleep periods of 24-hour ambulatory monitoring compared with the other three groups. A greater proportion of this group was in the hypertensive range (> or = 140/90 mm Hg) compared with the other groups (57% vs. 8%-29%). Low SES/high pessimism women also reported reduced available social support compared with the other three groups.