Tonic blood pressure modulates the relationship between baroreceptor cardiac reflex sensitivity and cognitive performance

This study explored the effects of tonic blood pressure on the association between baroreceptor cardiac reflex sensitivity and cognitive performance. Sixty female participants completed a mental arithmetic task. Baroreceptor reflex sensitivity was assessed using sequence analysis. An interaction was found, indicating that the relationship between baroreceptor reflex sensitivity and cognitive performance is modulated by blood pressure levels. Reflex sensitivity was inversely associated to performance indices in the subgroup of participants with systolic blood pressure above the mean, whereas the association was positive in participants with systolic values below the mean. These results are in accordance with the findings in the field of pain perception and suggest that tonic blood pressure modulates the inhibitory effects of baroreceptor stimulation on high central nervous functions.     

Blood pressure and the perception of illusive pain

Numerous studies have documented an inverse relationship between blood pressure and sensitivity to experimental nociceptive stimulation. The present study aimed to investigate possible associations between blood pressure and the occurrence and intensity of paradoxical pain induced by the thermal grill paradigm. Thirty‐one healthy subjects were stimulated three times for 1 min with the nonnoxious temperatures of 15°C and 41°C set at the interlaced cold and warm bars of a water bath‐driven thermal grill. Blood pressure and heart rate were recorded concomitantly. On account of previous observations of an association between the sensitivity of the cardiac baroreflex and pain perception, this parameter was additionally obtained. Numerical rating scales were used to quantify subjective pain intensity and pain unpleasantness; subjects were classified as responders and nonresponders to thermal grill stimulation based on pain intensity ratings. Responders exhibited lower systolic and diastolic blood pressure than nonresponders, and inverse linear associations arose between blood pressure and pain intensity and unpleasantness. Baroreflex sensitivity was unrelated to pain ratings. The findings confirmed the hypothesis of a blood pressure dependence of paradoxical pain and support the notion that the cardiovascular and pain regulatory systems interact not only in the processing of pain elicited by noxious input, but also in nonnoxiously generated illusive pain. While this finding is not consistent with the assumption of an involvement of the baroreflex system in mediating the observed interaction, psychological traits and neurochemical factors are alternatively considered.     

Reduced baroreflex cardiac sensitivity predicts increased cognitive performance

Abstract This study evaluated the relationship between baroreceptor reflex sensitivity and cognitive performance. Twenty normal subjects performed the Uchida-Kraepelin test, a serial arithmetic task. Baroreceptor reflex sensitivity during a 5-min Uchida-Kraepelin test was assessed in minute periods by spectral analysis using the maximum-entropy method. During the task, baroreceptor reflex sensitivity was significantly reduced. There was an inverse between-subjects association between baroreceptor reflex sensitivity and the level of performance (number of additions completed) both at different time periods of the Uchida-Kraepelin test and during the whole task (r=-.51). This finding supports the existence of a pathway mediating mutual cardiovascular-central nervous system influences through the baroreceptors, establishing an essential mechanism facilitating adaptive reactions to stressful conditions.     

The relationship between resting blood pressure and acute pain sensitivity: effects of chronic pain and alpha-2 adrenergic blockade

This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure × Participant Type × Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug × Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type × Systolic Blood Pressure interactions (P’s < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.     

The behavioral impact of baroreflex function: A review

The baroreflex consists of a negative feedback loop adjusting heart activity to blood pressure fluctuations. This review is concerned with interactions between baroreflex function and behavior. In addition to changes in baroreflex cardiac control subject to behavioral manipulations, interindividual differences in reflex function predicted psychological and central nervous features. The sensitivity of the reflex was inversely related to cognitive performance, evoked potential amplitudes, experimental pain sensitivity, and the severity of clinical pain. Possible variables moderating the strength of the associations are tonic blood pressure, gender, and psychiatric disease. It is suggested that these observations reflect inhibition of higher brain function by baroreceptor afferents. While in many cases increased baroreflex function implies stronger inhibition, individual and situational factors modulate the behavioral impact of cardiac regulation.     

Effects of cardiopulmonary baroreceptor activation on pain may be moderated by risk for hypertension

Cardiopulmonary baroreceptor stimulation may modulate pain, though the literature is much smaller than research showing that sinoaortic baroreceptor stimulation can buffer pain. To examine the possibility that risk for established high blood pressure may moderate the effects of cardiopulmonary baroreceptor stimulation on pain, 22 borderline hypertensive and 18 normotensive men participated in a laboratory experiment. Group differences in blood pressure were documented by 24-h ambulatory blood pressure recording. Ratings of the intensity of acute heat pain were influenced by both group membership and leg position. Passive elevation of the legs, a technique that stimulates cardiopulmonary baroreceptors, reduced ratings of heat pain though only among borderline hypertensives. Alteration of pain sensitivity may reflect the development of the hypertensive process.     

Sympathetic nervous response to induced fall and rise of arterial blood pressure in anesthetized rabbits

Summary The baroreceptor reflex is thought to counteract both a rise and a fall in arterial blood pressure, but the evidence for this is incomplete. In 19 anesthetized rabbits, the relationship between blood pressure/aortic nerve activity and efferent sympathetic activity in renal and splanchnic nerves was therefore investigated during induced rise and fall of arterial pressure. Baroreceptor activity increased and sympathetic activity decreased with raised pressure. In contrast, reduction of baroreceptor activity during acute hemorrhagic hypotension had little or no effect on activity in the two sympathetic nerves. Following complete barodenervation, however, sympathetic activity rose on average to 238% of control values. We therefore conclude that the baroreceptor reflex mainly counteracts a rise in arterial blood pressure. Reduction of baroreceptor activity in the first few minutes of acute hemorrhagic hypotension does not lead to increased sympathetic activity. The small activity remaining in baroreceptor nerves at low pressures had a very potent sympathetic inhibitory effect.     

Carotid baroreflex sensitivity at rest and during psychological stress in offspring of hypertensives and non-twin sibling pairs

The baroreceptor reflexes of 38 young adult males were mechanically stimulated by negative external cervical pressure during a mental arithmetic task and pre-stress and post-stress relaxation periods. The subjects comprised 19 pairs of non-twin siblings. Baroreflex sensitivity was significantly less pronounced during arithmetic. Using non-invasive techniques, this finding replicates several others indicating a damping of the baroreceptor reflux during stress. More importantly, analyses of sibling similarities also revealed significant familiality of baroreflex sensitivity, independent of age, body mass, pressure applied and baseline heart rate. To examine the relationship between baroreflex sensitivity and parental history of hypertension, 21 young adult males with a parental history and 25 without participated in a second experiment. The two groups were not significantly different in resting baroreflex sensitivity. However, sensitivity was damped to a significantly greater degree during mental arithmetic in offspring of hypertensives, offering one possible explanation for their greater blood pressure reactivity to stress. These results suggest that familial influences may effect baroreflex sensitivity and, possibly as a result, blood pressure reactivity and risk for hypertension.     

Blood pressure and pain sensitivity in children and adolescents

Elevated blood pressure is associated with diminished pain sensitivity. While this finding is well established in adults, it is less clear when the relation between blood pressure and pain sensitivity emerges across the life course. Evidence suggests this phenomenon may exist during childhood. Children (N = 309; 56% boys) aged 10–15 years and their parents participated. Blood pressure readings were taken during a resting baseline. Maximum pain intensity was rated using a visual analogue scale (rated 0–10) in response to a finger prick pain induction. Parent‐measured resting blood pressure was inversely associated with boys' pain ratings only. Cross‐sectionally, lower pain ratings were related to higher SBP, univariately. Longitudinally, pain ratings predicted higher DBP, even after controlling for covariates. Determining when and how the relation between blood pressure and pain sensitivity emerges may elucidate the pathophysiology of hypertension.     

Baroreceptor sensitivity in two-week-old rat pups: effects of nutrient deprivation and sino-aortic denervation

Resting cardiac rates are reduced 40% by nutrient deprivation in two-week-old rats while arterial pressure is maintained at stable levels. Previous evidence implicated arterial baroreceptors and suggested the hypothesis that the cardiac rate changes result from increased baroreceptor sensitivity following nutrient deprivation. In order to test this hypothesis, cardiac reflex responses were elicited by graded doses of phenylephrine and sodium nitroprusside before and after nutrient deprivation. Although cardiac rate decelerations in response to phenylephrine were greater in fed pups (p less than 0.05) and acceleration in response to nitroprusside were greater in the deprived condition (p less than 0.01), these could be attributed to 'ceiling' and 'floor' effects of the resting cardiac rates characteristic of the two nutrient conditions. Sino-aortic denervation eliminated cardiac reflex responses, substantiating their dependence on baroreceptor afferents. Regression analysis of cardiac reflex responses to arterial pressure changes failed to show changes in baroreceptor sensitivity that would support the hypothesis. Alternate mechanisms mediating the nutrient effect on cardiac rate (e.g., involving neural and peptide hormonal pathways) should be pursued.     

Baroreceptor Stimulation Alters Pain Sensation Depending on Tonic Blood Pressure

It has been hypothesized that activation of the baroreceptor reflex arc, by its central nervous inhibitory effects, is involved in an operant learning mechanism of blood pressure elevation. The present study investigated the effects of mechanical stimulation of the baroreceptors in the carotid sinus on pain threshold and electrical brain activity in two groups of humans with different tonic blood pressure levels. In normotensives, baroreceptor stimulation lowered pain threshold as compared to a control condition, while borderline hypertensives tolerated more intense electric stimulation when baroreceptors were activated. A marked reduction of the contingent negative variation in anticipation of the aversive stimulation accompanied baroreceptor stimulation, probably a consequence of baroreceptor afferent impulses exerted via brainstem centers to cerebral cortex. The distribution of the potential change across the scalp depended on the tonic blood pressure, indicating differences in brain functioning between normotensives and borderline hypertensives. The present results suggest that the hypothesis of an operantly-conditioned blood pressure elevation under stress may be valid only in subjects with a predisposition for essential hypertension.     

Effects of isometric exercise on pain are mediated by blood pressure

Sensitivity to pain is reduced during exercise. The underlying mechanism has yet to be established. One possibility is that a baroreceptor-related mechanism may contribute to this exercise-induced hypoalgesia phenomenon. Accordingly, this study examined whether increases in arterial blood pressure during graded isometric exercise, which activate baroreceptors in the aortic arch and carotid sinus, could account for any effects of exercise on pain in 24 normotensive young men. Electrocutaneous stimuli were delivered to the sural nerve while participants performed isometric handgrip exercise at 1%, 15%, and 25% of their maximum voluntary contraction (MVC). Participants provided a pain intensity rating immediately following the delivery of each stimulus. Nociceptive flexion reflex (NFR) responses and thresholds were also determined to provide objective physiological correlates of pain. Pain ratings were attenuated by graded isometric exercise in a linear fashion, whereas nociceptive flexion reflex responses and thresholds were unchanged by exercise. Blood pressure increased in proportion to the force of the contraction. Mediational analyses using analyses of covariance indicated that the reduction in pain with exercise was substantially accounted for by the magnitude of the blood pressure response. These findings are consistent with an arterial baroreceptor inhibition mechanism for exercise-induced hypoalgesia.     

The vasomotor component of the carotid sinus baroreceptor reflex in the cat during stimulation of the hypothalamic defence area

1. The effect of moderate intensities of stimulation of the hypothalamic defence area on the baroreceptor reflex has been investigated in the cat by comparing the responses of arterial blood pressure and perfusion pressure of the isolated hind-limb muscle bed perfused at constant volume inflow, when the isolated carotid sinus was subjected to a series of non-pulsatile pressures with and without simultaneous hypothalamic stimulation.2. In the absence of hypothalamic stimulation the characteristic sigmoid curves relating sinus pressure to blood pressure or muscle perfusion pressure were obtained.3. With simultaneous stimulation of the hypothalamus a similar sigmoid relationship was found. There was no evidence of any reduction in the over-all power or maximum sensitivity of the baroreceptor reflex.4. However, in those cats which had been atropinized to abolish the cholinergically mediated muscle vasodilatation, the curves obtained during hypothalamic stimulation were displaced in such a manner as to suggest that, while baroreceptor modulation of vasoconstrictor tone continued during defence area stimulation, the blood pressure regulating mechanism had been ;reset' so that, within the physiological range of sinus pressures, any given level of sinus pressure was associated with a greater vasoconstrictor tone.5. In non-atropinized cats there was little displacement of the curves relating sinus pressure to blood pressure, while the curves relating sinus pressure to muscle perfusion pressure were displaced in the opposite direction so that over-all muscle vascular resistance was less than normal at each level of sinus pressure.     

Does gender affect the relation between blood pressure and pain sensitivity?

High resting blood pressure is associated with decreased pain sensitivity. This study was designed to explore this relation in young, normotensive men and women. Twenty-nine women (mean age 19.1, range 18-29) and 26 men (mean age 19.3, range 18-25) rested for 10 min while systolic, diastolic, and mean arterial blood pressures were measured. They were then asked to complete a 2-min cold pressor task. Participants were asked to fill out the short form of the McGill Pain Questionnaire immediately after the pain task. Hierarchical regression analyses were performed to predict pain sensitivity from resting blood pressure, gender, and the interaction of resting blood pressure and gender. Resting systolic blood pressure was a significant predictor of pain sensitivity. Gender and the interaction between resting blood pressure and gender were not related to pain sensitivity. This suggests that the relation between resting blood pressure and pain sensitivity may be similar in men and women, at least in response to a cold pressor challenge.     

Baroreflex “resetting” by arterial hypoxia in the renal and cardiac sympathetic nerves of the rabbit

1. Renal and cardiac sympathetic baroreflex functions were studied in sodium pentobarbitone anaesthetized rabbits given succinylcholine, during constant artificial ventilation with air and with hypoxic gas mixtures. Mean arterial pressure (MAP) was raised and lowered between values of 40 and 140 mm Hg by means of aortic and vena caval periovascular balloons and integrated sympathetic nerve activity (SNA) was recordered. 2. The relationship between MAP and SNA was sigmoid, with upper and lower plateau levels. The curves were defined by calculating median blood pressure, SNA Range and reflex gain. In both renal and cardiac sympathetics section of the carotid sinus and aortic nerves completely abolished the MAP-related changes in SNA. 3. The renal baroreflex curves were reset from control levels during hypoxia. Median blood pressure increased, as did SNA Range and gain. These effects were due to central interactions between arterial baroreceptor, arterial chemoreceptor and vagal afferent activity. 4. The cardiac sympathetic baroreflex curves were shifted in the opposite direction from control with reduction in median blood pressure, SNA Range and reflex gain. These changes were due to chemoreceptor-arterial baroreceptor interactions. 5. Arterial hypoxia thus evokes a differentiated pattern of baroreflex resetting in the renal and cardiac sympathetic montoneuron pools with differing changes in neural response range and sensitivity to arterial pressure changes.     

Psychophysiology of arterial baroreceptors and the etiology of hypertension.

Arterial baroreceptors are sensitive to blood pressure dependent blood vessel dilation. They play a key role in the short term regulation of blood pressure. Their impact on psychological and psychophysiological aspects is of increasing interest. The review focuses on experimental techniques for the controlled baroreceptor manipulation. Results from the application of these techniques show that baroreceptor activation influences the cardiovascular system as well as central nervous functioning: Behavioral and electrophysiological measures of arousal, low level reflexes and pain responses are modulated through baroreceptor manipulation. The observation of an overall dampening ('barbiturate like') effect of baroreceptor activity led Dworkin et al. formulate the theory of learned hypertension: Subjects might experience blood pressure dependent baroreceptor activation as stress and pain relieving. High blood pressure periods become negatively reinforced. Phasic high blood pressure might develop as a coping strategy. Data from a longitudinal human study supporting this theory are reported.     

Relationship between the baroreceptor reflex and the variability of arterial pressure and of the heart beat period in rats with arterial hypertension

The relationship between depression of the cardiochronotropic component of the baroreceptor reflex and arterial pressure and heart beat variabilities was investigated in normotensive rats and rats with renal hypertension (one kidney — one clamp). In the hypertensive rats, the arterial pressure and heart rate were both increased and more variable, while the cardiochronotropic component of the baroreceptor reflex was depressed. No cause-effect relationship between baroreceptor reflex attenuation and increased variability of hemodynamic parameters was found in this rat model of arterial hypertension. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, No. 5, pp. 474–476, May, 1995 Presented by B. I. Tkachenko, Member of the Russian Academy of Medical Sciences     

Altered cardiovascular/pain regulatory relationships in chronic pain

In healthy individuals, there is an inverse relationship between resting blood pressure (BP) and pain sensitivity. This study examined possible dysregulation of this adaptive relation in chronic pain patients, and tested whether the extent of this dysregulation is a function of pain duration, Continuous resting BP_s were assessed for 5 min after a 5-min rest period in 121 chronic benign pain patients. Unlike the inverse relationship observed previously in normals, mean resting diastolic BP_s during the assessment period were correlated positively with ratings of pain severity. A Pain Duration x Systolic BP i nteraction emerged (p > .05) such that the magnitude of the BP-pain relation was greatest in patients with the longest duration of pain, r(38) = .50, p > .001. A hypothesized progressive alteration in endogenous pain regulatory systems in chronic pain patients was supported. A possible role of endogenous opioid dysfunction in accounting for these alterations is discussed. This investigation was supported by Grant BRSG S07 RR05366-28. awarded to John W. Burns by the Biomedical Research Grant Program, Division of Research Resources, National Institutes of Health. We thank Kathleen Kiselica and Ronald Pawl for allowing access to their patients at the Center for Rehabilitation at Lake Forest Hospital in Lake Forest, IL.