Role of central command in carotid baroreflex resetting in humans during static exercise

The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure ( P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure ( P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves ( P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.     

The role of the menstrual cycle phase in pain perception before and after an isometric fatiguing contraction

The purpose of this study was to compare exercise-induced analgesia in young women after a fatiguing isometric contraction during different phases of the menstrual cycle. Twenty female subjects performed a submaximal (25% maximal voluntary contraction) isometric contraction until task failure during both the mid-follicular and mid-luteal phases of their menstrual cycle. Pain perception (i.e., pain threshold and pain ratings) was measured before and after the isometric fatiguing contraction. Other measures included mean arterial pressure, heart rate, and anxiety levels. Time to task failure of the fatiguing contraction was similar for the two phases of the menstrual cycle. Following the performance of the isometric contraction: (1) pain thresholds increased and pain ratings decreased; (2) anxiety levels increased; and (3) mean arterial pressure and heart rate increased. These changes were not dependent on the phase of the menstrual cycle. Thus, the menstrual cycle phase does not influence the magnitude of exercise-induced analgesia.     

Central modulation of exercise-induced muscle pain in humans

The purpose of the current study was to determine if exercise-induced muscle pain is modulated by central neural mechanisms (i.e. higher brain systems). Ratings of muscle pain perception (MPP) and perceived exertion (RPE), muscle sympathetic nerve activity (MSNA), arterial pressure, and heart rate were measured during fatiguing isometric handgrip (IHG) at 30% maximum voluntary contraction and postexercise muscle ischaemia (PEMI). The exercise trial was performed twice, before and after administration of naloxone (16 mg intravenous; n = 9) and codeine (60 mg oral; n = 7). All measured variables increased with exercise duration. During the control trial in all subjects ( n = 16), MPP significantly increased during PEMI above ratings reported during IHG (6.6 ± 0.8 to 9.5 ± 1.0; P < 0.01). However, MSNA did not significantly change compared with IHG (7 ± 1 to 7 ± 1 bursts (15 s)⁻¹), whereas mean arterial blood pressure was slightly reduced (104 ± 4 to 100 ± 3 mmHg; P < 0.05) and heart rate returned to baseline values during PEMI (83 ± 3 to 67 ± 2 beats min⁻¹; P < 0.01). These responses were not significantly altered by the administration of naloxone or codeine. There was no significant relation between arterial blood pressure and MSNA with MPP during either IHG or PEMI. A second study ( n = 8) compared MPP during ischaemic IHG to MPP during PEMI. MPP was greater during PEMI as compared with ischaemic IHG. These findings suggest that central command modulates the perception of muscle pain during exercise. Furthermore, endogenous opioids, arterial blood pressure and MSNA do not appear to modulate acute exercise-induced muscle pain.     

Human investigations into the arterial and cardiopulmonary baroreflexes during exercise

After considerable debate and key experimental evidence, the importance of the arterial baroreflex in contributing to and maintaining the appropriate neural cardiovascular adjustments to exercise is now well accepted. Indeed, the arterial baroreflex resets during exercise in an intensity-dependent manner to continue to regulate blood pressure as effectively as at rest. Studies have indicated that the exercise resetting of the arterial baroreflex is mediated by both the feedforward mechanism of central command and the feedback mechanism associated with skeletal muscle afferents (the exercise pressor reflex). Another perhaps less appreciated neural mechanism involved in evoking and maintaining neural cardiovascular responses to exercise is the cardiopulmonary baroreflex. The limited information available regarding the cardiopulmonary baroreflex during exercise provides evidence for a role in mediating sympathetic nerve activity and blood pressure responses. In addition, recent investigations have demonstrated an interaction between cardiopulmonary baroreceptors and the arterial baroreflex during dynamic exercise, which contributes to the magnitude of exercise-induced increases in blood pressure as well as the resetting of the arterial baroreflex. Furthermore, neural inputs from the cardiopulmonary baroreceptors appear to play an important role in establishing the operating point of the arterial baroreflex. This symposium review highlights recent studies in these important areas indicating that the interactions of four neural mechanisms (central command, the exercise pressor reflex, the arterial baroreflex and cardiopulmonary baroreflex) are integral in mediating the neural cardiovascular adjustments to exercise.     

Modulation of the human nociceptive flexion reflex across the cardiac cycle

Carotid baroreceptor stimulation has been shown to dampen pain. This study tested, in 40 normotensive adults, the hypothesis that pain is lower during systole when arterial baroreceptor stimulation is maximal than diastole when stimulation is minimal. The sural nerve was stimulated electrocutaneously to obtain a nociceptive flexion reflex (NFR) threshold, and then stimulation was delivered for 28 trials at 100% NFR threshold at seven intervals after the R-wave. Nociceptive responding was indexed by electromyographic (EMG) activity elicited in the biceps femoris. Significant variations in EMG activity occurred across the cardiac cycle, with less activity midcycle, indicating that the NFR response was attenuated during systole compared to diastole. Stimulation of baroreceptors by natural changes in blood pressure during the cardiac cycle dampened nociception, and accordingly, the data support the arterial baroreflex mechanism of hypertensive hypoalgesia.     

The combined effect of the cold pressor test and isometric exercise on heart rate and blood pressure

Summary The purpose of this study was to determine if the cold pressor test during isometric knee extension [15% of maximal voluntary contraction (MVC)] could have an additive effect on cardiovascular responses. Systolic and diastolic blood pressures, heart rate and pressure rate product were measured in eight healthy male subjects. The subjects performed the cold pressor tests and isometric leg extensions singly and in combination. The increases of systolic and diastolic blood pressure during isometric exercise were of almost the same magnitude as those during the cold pressor test. The responses of arterial blood pressure, and heart rate to a combination of the cold pressor test and isometric knee extension were greater than for each test separately. It is suggested that this additional effect of cold immersion of one hand during isometric exercise may have been due to vasoconstriction effects in the contralateral unstressed limb. In summary, the circulatory effects of the local application of cold during static exercise at 15% MVC were additive.     

Effects of opioid blockade on nociceptive flexion reflex thresholds and nociceptive responding in hypertensive and normotensive individuals

Hypertension and risk for hypertension have been associated with reduced pain sensitivity. It has been hypothesised that endogenous opioids contribute to this hypertensive hypoalgesia. The nociceptive flexion reflex can be used as a tool to investigate modulation of nociceptive transmission at spinal level. The current study employed a double-blind placebo-controlled design to compare the effects of naltrexone, an opioid antagonist, and placebo on nociceptive flexion reflex thresholds and nociceptive responding in unmedicated patients with essential hypertension and normotensive individuals. Neither nociceptive flexion reflex thresholds nor nociceptive responding differed between hypertensives and normotensives during placebo or naltrexone. These data provide no support for the hypothesis that essential hypertension is characterised by higher levels of endogenous opioids in the central nervous system and reveal no association between blood pressure status and nociceptive flexion reflex responses.     

Circulatory effects of isometric muscle contractions,performed separately and in combination with dynamic exercise

Studies on central circulation and regional blood flow were performed in healthy male volunteers at rest, during sustained isometric forearm contraction at 20% of MVC, during dynamic leg exercise (100 W) and during combined isometric and dynamic exercise. In 10 subjects pulmonary oxygen uptake, arterio-venous oxygen difference, heart rate, leg blood flow and blood pressures in the pulmonary and subclavian arteries and in the right atrium were measured. In 4 of these subjects the temperature was measured in mixed venous blood and in subcutaneous tissue in an attempt to further analyse the blood flow distribution through central versus peripheral parts of the circulatory system. In 5 other subjects the splanchnic blood flow was estimated by hepatic vein catheterization and dye dilution technique at rest and during isometric forearm contraction. It was found that cardiac output, oxygen uptake, heart rate and arterial blood pressure all increased in response to isometric contraction. Quantitatively the changes in heart rate and cardiac output induced by a sustained contraction were more marked when the contraction was performed separately than when it was added to dynamic exercise. In spite of the increased arterial pressure, the leg blood flow did not increase significantly. Neither did the splanchnic blood flow increase in response to hand-grip contraction. The blood temperature in the pulmonary artery rose during isolated dynamic exercise. Isometric exercise, however, caused a blood temperature fall and a rise in subcutaneous temperature indicating an increased blood flow through the skin. It is concluded that during sustained isometric muscle contraction

1. the blood flow increase is mainly distributed to peripheral circulatory areas,
2. a concomitant dynamic exercise interferes with the circulatory adaptation only to a small extent.

     

The pressor response to voluntary and electrically evoked isometric contractions in man

Summary Blood pressure and heart rate changes during sustained isometric exercise were studied in 11 healthy male volunteers. The responses were measured during voluntary and involuntary contractions of the biceps brachii at 30% of maximal voluntary contraction (MVC), and the triceps surae at 30% and 50% MVC. Involuntary contractions were evoked by percutaneous electrical stimulation of the muscle.Measurements of the time to peak tension of maximal twitch showed the biceps brachii (67.0±7.9 ms) muscle to be rapidly contracting, and the triceps surae (118.0±10.5 ms) to be slow contracting. The systolic and diastolic blood pressures increased linearly throughout the contractions, and systolic blood pressure increased more rapidly than diastolic. There was no significant difference in response to stimulated or voluntary contractions, nor was there any significant difference between the responses to contractions of the calf or arm muscles at the same relative tension.In contrast the heart rate rose to a higher level (P<0.01) in the biceps brachii than the triceps surae at given % MVC, and during voluntary compared with the electrically evoked contractions in the two muscle groups.It was concluded that the arterial blood pressure response to isometric contractions, unlike heart rate, is primarily due to a reflex arising within the active muscles (cf. Hultman and Sjöholm 1982) which is associated with relative tension but independent of contraction time and muscle mass.     

Examination of the dose-response relationship between pain perception and blood pressure elevations induced by isometric exercise in men and women

The purpose of this study was to examine exercise-induced hypoalgesia (EIH) in men and women, and whether different magnitudes of BP elevations induced by isometric exercise systematically influenced pain perception. Twenty-five men and 25 women performed isometric exercise at 25% MVC for 1-min, 3-min, and 5-min while BP and pain perception were assessed. Results indicated that BP was significantly elevated (p < 0.05) by isometric exercise in a dose-response manner. Pain thresholds were found to be elevated while pain ratings were lower (p < 0.05) immediately following isometric exercise but not in a dose-response manner. It was concluded that isometric exercise produced EIH in men and women, and there was not a dose-response relationship between BP and EIH.     

The human nociceptive flexion reflex threshold is higher during systole than diastole

A baroreflex mechanism may explain hypertensive hypoalgesia. At rest, arterial baroreceptors are stimulated during the systolic upstroke of the pressure pulse wave. This study examined the effects of naturally occurring variations in baroreceptor activity during the cardiac cycle on an objective measure of pain, the nociceptive flexion reflex (NFR). Two interleaved up-down staircase procedures determined separate NFR thresholds during systole and diastole in 36 healthy, normotensive young adults. On odd-numbered trials, the sural nerve was stimulated electrocutaneously at R + 300 ms whereas on even-numbered trials, stimulation was delivered at R + 600 ms. The NFR threshold was higher at R + 300 ms than R + 600 ms. In contrast, stimulus intensity ratings did not differ between R + 300 ms and R + 600 ms. Stimulation of baroreceptors by natural increases in blood pressure during the systolic phase of the cardiac cycle was associated with dampened nociception.     

Heart rate and blood pressure responses to isometric exercise in young and older men

The aim of this study was to examine the isometric endurance response and the heart rate and blood pressure responses to isometric exercise in two muscle groups in ten young (age 23–29 years) and seven older (age 54–59 years) physically active men with similar estimated forearm and thigh muscle masses. Isometric contractions were held until fatigue using the finger flexor muscles (handgrip) and with the quadriceps muscle (one-legged knee extension) at 20%, 40%, and 60% of the maximal voluntary contraction (MVC). Heart rate and arterial pressure were related to the the individual's contraction times. The isometric endurance response was longer with handgrip than with one-legged knee extension, but no significant difference was observed between the age groups. The isometric endurance response averaged 542 (SEM 57), 153 (SEM 14), and 59 (SEM 5) s for the handgrip, and 276 (SEM 35), 94 (SEM 10) and 48 (SEM 5) s for the knee extension at the three MVC levels, respectively. Heart rate and blood pressure became higher during one-legged knee extension than during handgrip, and with increasing level of contraction. The older subjects had a lower heart rate and a higher blood pressure response than their younger counterparts, and the differences were more apparent at a higher force level. The results would indicate that increasing age is associated with an altered heart rate and blood pressure response to isometric exercise although it does not affect isometric endurance.     

Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

Partial blockade of skeletal muscle somatosensory afferents attenuates baroreflex resetting during exercise in humans

During exercise, the carotid baroreflex is reset to operate around the higher arterial pressures evoked by physical exertion. The purpose of this investigation was to evaluate the contribution of somatosensory input from the exercise pressor reflex to this resetting during exercise. Nine subjects performed seven minutes of dynamic cycling at 30 % of maximal work load and three minutes of static one-legged contraction at 25 % maximal voluntary contraction before (control) and after partial blockade of skeletal muscle afferents with epidural anaesthesia. Carotid baroreflex function was assessed by applying rapid pulses of hyper- and hypotensive stimuli to the neck via a customised collar. Using a logistic model, heart rate (HR) and mean arterial pressure (MAP) responses to carotid sinus stimulation were used to develop reflex function stimulus-response curves. Compared with rest, control dynamic and static exercise reset carotid baroreflex-HR and carotid baroreflex-MAP curves vertically upward on the response arm and laterally rightward to higher operating pressures. Inhibition of exercise pressor reflex input by epidural anaesthesia attenuated the bi-directional resetting of the carotid baroreflex-MAP curve during both exercise protocols. In contrast, the effect of epidural anaesthesia on the resetting of the carotid baroreflex-HR curve was negligible during dynamic cycling whereas it relocated the curve in a laterally leftward direction during static contraction. The data suggest that afferent input from skeletal muscle is requisite for the complete resetting of the carotid baroreflex during exercise. However, this neural input appears to modify baroreflex control of blood pressure to a greater extent than heart rate.     

Aversive event unpredictability causes stress‐induced hypoalgesia

Temporal predictability, or knowing when a noxious stimulus will occur, has been implicated in stress‐induced hypoalgesia, but the contribution of event predictability, or knowing what the stimulus will be, remains poorly understood. To address this issue, we examined the effects of event predictability on pain intensity ratings and nociceptive flexion reflex responses. Participants repeatedly experienced five intensities of electrocutaneous stimulation, ranging from nonpainful to extremely painful, delivered either randomly (unpredictability group) or blocked (predictability group) with no cues provided. Unpredictable shocks produced the lowest pain ratings while evoking the highest flexion reflex responses. Moreover, anticipatory heart rate data indicated that unpredictable trials were the most physiologically arousing. Our findings show that uncertainty about the upcoming stimulus intensity is stressful and unpleasant, thereby causing hypoalgesia and reflex potentiation.     

Brief submaximal isometric exercise improves cold pressor pain tolerance

Exercise-induced hypoalgesia (EIH), or the inhibition of pain following physical exercise, has been demonstrated in adults, but its mechanisms have remained unclear due to variations in methodology. This study aimed to address methodological imitations of past studies and contribute to the literature demonstrating the generalizability of EIH to brief submaximal isometric exercise and cold pressor pain. Young adults (n = 134) completed a baseline cold pressor trial, maximal voluntary contraction (hand grip strength) assessment, 10-min rest, and either a 2-min submaximal isometric handgrip exercise or a sham exercise in which no force was exerted, followed by a cold pressor posttest. Results indicated that cold pressor pain tolerance significantly increased during the exercise condition, but not during the sham exercise condition. Exercise did not affect pain intensity and marginally affected pain unpleasantness ratings. These findings suggest that submaximal isometric exercise can improve cold pressor pain tolerance but may have an inconsistent analgesic effect on ratings of cold pressor pain.     

Modulation of the human nociceptive reflex by cyclic movements

During static conditions the nociceptive reflex is known to vary as a function of, for example, the stimulus position, stimulus intensity, and muscle contraction. The aim of the present human study was to investigate whether the reflex and the corresponding perception of pain are modulated by cyclic movements of the limb involved. Reflexes, evoked by nociceptive electric stimulation of the sural nerve, were recorded from the biceps femoris and the rectus femoris muscles in eight volunteers. Four different experiments were performed to compare the nociceptive reflex and pain score elicited during active isometric/dynamic flexion/extension of the knee joint. The amplitudes of the reflexes were largest for the dynamic conditions. The reflexes, evoked during dynamic extension and isometric contraction of the rectus femoris muscle, had the shortest latencies but the recordings from the biceps femoris muscle were larger than from the rectus femoris muscle. Knee joint angle recordings showed that the largest angle variations occurred for the dynamic conditions and were only marginally disturbed for the isometric conditions. A given stimulus intensity evoked the highest pain intensity during isometric contractions. This indicates that there would seem to be no causal relationship between the size of the nociceptive reflex and the pain intensity.     

The influence of straining maneuvers on the pressor response during isometric exercise

Summary Experiments were performed to determine to what extent increments in esophageal and abdominal pressure would have on arterial blood pressure during fatiguing isometric exercise. Arterial blood pressure was measured during handgrip and leg isometric exercise performed with both a free and occluded circulation to active muscles. Handgrip contractions were exerted at 33 and 70% MVC (maximum voluntary contraction) by 4 volunteers in a sitting position and calf muscle contractions at 50 and 70% MVC with the subjects in a kneeling position. Esophageal pressure measured at the peak of inspirations did not change during either handgrip or leg contractions but peak expiratory pressures increased progressively during both handgrip and leg contractions as fatigue occurred. These increments were independent of the tensions of the isometric contractions exerted. Intra-abdominal pressures measured at the peak of either inspiration or expiration did not change during inspiration with handgrip contractions but increased during expiration. During leg exercise, intraabdominal pressures increased during both inspiration and expiration, reaching peak levels at fatigue. The arterial blood pressure also reached peak levels at fatigue, independent of circulatory occlusion and tension exerted, averaging 18.5–20 kPa (140–150 mm Hg) for both handgrip and leg contrations. While blood pressure returned to resting levels following exercise with a free circulation, it declined by only 2.7–3.8 kPa after leg and handgrip exercise, respectively, during circulatory occlusion. These results indicate that straining maneuvers contribute 3.5 to 7.8 kPa to the change in blood pressure depending on body position.     

Effects of microgravity on interstitial muscle receptors affecting heart rate and blood pressure during static exercise

Summary Afferent nerve fibers from receptors situated in the interstitium of skeletal muscles can induce cardiovascular reflexes. It has been shown that these interstitial muscle receptors are also sensitive to the local state of hydration: increased heart rates and blood pressure values were seen during dynamic and static exercise after local dehydration on earth. Since weightlessness leads to a persisting fluid loss in the lower part of the body, we hypothesized that leg exercise in space would augment heart rate and blood pressure responses to a similar extent as during local, interstitial dehydration on earth. Initial measurements during weightlessness were obtained in one subject after 6 days of space flight. Heart rate and blood pressure responses to light static foot plantar flexion (18% of maximal voluntary contraction) were recorded in two sessions. To eliminate the influence of muscle perfusion, exercise was performed during a period of arterial occlusion obtained by means of pneumatic cuffs at mid-thigh level. Identical protocols were used in the pre- and postflight controls, which were performed both in the sitting posture and in a –90° tilted sitting posture assumed 30–40 min before arterial occlusion. During weightlessness the exercise responses of heart rate and systolic and diastolic blood pressure closely followed the tracings obtained with the tilted sitting posture on ground. The response amplitudes in these states of reduced lower limb volumes (about 20/min and 20 mmHg, respectively) exceeded the responses in the supine position by a factor of at least 2. Enhancement of cardiovascular reflexes following local fluid losses of skeletal muscles appears to be a general phenomenon that can also be seen during weightlessness.Abbreviations EMG Electromyogram - LBNP Lower body negative pressure - MVC Maximal voluntary contraction     

The exercise pressor response to sustained handgrip does not augment blood flow in the contracting forearm skeletal muscle

Previous studies have advanced the concept that during sustained handgrip (SHG) reflex increases in blood pressure are able to partially offset increases in tissue pressure and thus effectively maintain increases in muscle blood flow during mild to moderate levels of sustained handgrip. However, this concept is based upon measurements of blood flow to the entire forearm. The aim of this study was to evaluate this concept by simultaneously measuring time-dependent changes in systemic arterial pressure and blood flow in an active muscle during the actual period of exercise. To accomplish this aim, we measured ¹³³Xenon washout from the extensor carpi radialis longus muscle over 3 min of SHG at 15, 30 and 45% of maximal voluntary contraction (MVC). During sustained handgrip at 15% MVC, muscle blood flow increased more than 20 fold from rest to exercise (P < 0.05), even though mean arterial pressure increased by only 12 ± 4 mmHg. This large exercise-induced hyperaemia was abolished during SHG at both 30 and 45% MVC, despite large and progressive increases in mean arterial pressure of 29 ± 3 and 54 ± 5 mmHg, respectively. We conclude that at levels of handgrip above 15% MVC blood pressure ceases to be an important determinant of blood flow in the active skeletal muscle. Importantly, the increases in forearm blood flow that have been reported previously with such levels of static handgrip do not appear to be directed to the most active muscle.