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Journal of Physiology (2002), 544.1, pp. 285-292
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.019596

Inhibition of human muscle sympathetic activity by sensory stimulation

Vincenzo Donadio, Mika Kallio, Tomas Karlsson, Magnus Nordin and B. Gunnar Wallin

	ABSTRACT

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Surprising sensory stimuli causing arousal are known to evoke short-lasting activation of human sympathetic activity in skin but not in muscle nerves; anecdotal observations suggest that there may even be an inhibition of muscle sympathetic nerve activity (MSNA). To test this hypothesis we recorded multiunit MSNA in the peroneal nerve in 19 subjects aged 19-71 years, while sensory stimuli, consisting of either an electrical skin stimulus to a finger or a visual flash, were delivered repeatedly with intervals of approximately 20 s. The stimuli were given either 200 or 400 ms after the R wave of the electrocardiogram. Dummy stimuli, consisting of trigger pulses without sensory stimulation served as controls. Electrical skin resistance reductions were monitored from the palm of a hand as electrodermal signs of arousal-induced cutaneous sympathetic activity. On a group basis both types of sensory stimuli attenuated the amplitude of one or two bursts of MSNA, while no such effects occurred after dummy stimuli. Individually, the inhibition was evoked by at least one stimulus modality or delay in 16 subjects whereas in three subjects no significant inhibition occurred. Skin resistance responses were evoked in all subjects. Some subjects responded to one, others to both stimulus modalities, and electrical stimuli were more effective than visual stimuli in causing MSNA inhibition as well as skin resistance reduction. On the other hand, electrodermal signs of arousal were equally common in subjects with and without inhibitory responses. We suggest that the MSNA inhibition evoked by sensory stimuli is an arousal effect which varies markedly between individuals.

(Received 5 March 2002; accepted after revision19 July 2002; first published online 16 August 2002)
Corresponding author B. G. Wallin: Department of Clinical Neurophysiology, Institute of Clinical Neuroscience, Sahlgren University Hospital, Göteborg S-413 45 , Sweden. Email: gunnar.wallin{at}neuro.gu.se

	INTRODUCTION

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Human muscle sympathetic nerve activity (MSNA) is composed of vasoconstrictor impulses grouped in pulse synchronous bursts which usually occur in sequences, preferentially during transient reductions of blood pressure (Delius et al. 1972). Changes of arterial baroreceptor firing induce opposite changes in the strength of MSNA (Wallin et al. 1975; Wallin & Eckberg, 1982) and in each subject an approximately constant baroreflex latency can be defined, i.e. a given sympathetic burst can always be related to a given cardiac cycle (Delius et al. 1972). Skin sympathetic nerve activity (SSNA), on the other hand, is composed of both vasomotor and sudomotor impulses and arterial baroreflex modulation of the activity is much less pronounced than for MSNA. Another prominent difference between the two types of activity is the difference in responsiveness to arousal: any unexpected stimulus evokes a single distinct discharge in SSNA but not in MSNA (Hagbarth et al. 1972). The difference in arousal-induced responses may be related to the difference in baroreceptor influence on the two types of activity: when afferent baroreceptor activity was unable to influence the spinal sympathetic motoneurones, skin stimuli were found to evoke clear discharges, not only in SSNA but also in MSNA (Fagius et al. 1985; Stjernberg et al. 1986).

Recently, transcranial magnetic stimulation of the cerebral cortex was found to have an inhibitory effect on MSNA: a single magnetic stimulus reduced the amplitude of the first or second MSNA burst after the stimulus (Macefield et al. 1998). At the same time, sympathetic effector recordings suggested that the stimulus had an excitatory effect on SSNA, which agrees with recent evidence from microneurographic recordings of SSNA (Silber et al. 2000) The inhibitory effect on MSNA was most prominent if the magnetic stimulus was delivered 200 or 400 ms after the R wave of the ECG, suggesting that the stimulus in some way potentiated the inhibitory effect of the afferent discharge from arterial baroreceptors. The mechanism underlying the inhibition was not studied specifically, but a direct cortical effect was considered to be more likely than an unspecific inhibition due to an arousal reaction. There are, however, anecdotal observations in the literature suggesting that peripheral stimuli may also inhibit one or two MSNA bursts. Thus, Delius et al. (1972) noted that sudden chest compression or electrical skin shocks could have this effect and Stjernberg et al. (1986) reported that MSNA bursts rarely occurred 0.25-1.75 s after an electrical skin stimulus. Against this background, the aim of the present study was to investigate if peripheral sensory stimuli (which are likely to cause arousal) will also inhibit MSNA in a similar way to transcortical magnetic stimulation. To this end we randomly delivered two types of sensory stimuli, either an electrical skin shock or a visual flash, and measured the effects on MSNA.

	METHODS

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The study group consisted of 19 healthy subjects taking no medication, three women and 16 men aged 19-71 years (mean 47 years). Nine subjects were below and 10 subjects were above 50 years of age. The experimental procedures were approved by the Human Ethics Committee at the University of Göteborg and all subjects gave their written, informed consent to the procedures, which conformed to the Declaration of Helsinki.

Measurements

Subjects were semi-reclining in a comfortable chair. ECG was recorded using Ag-AgCl electrodes on the chest. Changes in skin resistance (filter settings 0.3-100 Hz) were measured from the right hand via Ag-AgCl electrodes applied to the thenar eminence and the dorsum of the hand. EMG was recorded with Ag-AgCl electrodes taped to the skin over the left deltoid muscle.

Multiunit recordings of efferent post-ganglionic sympathetic nerve activity were obtained with an insulated tungsten microelectrode with a tip diameter of a few microns inserted into a muscle fascicle of the peroneal nerve, posterior to the fibular head. A low-impedance reference electrode was inserted subcutaneously a few centimetres away. The nerve signal was amplified ( 50 000), filtered (bandpass 700-2000 Hz) and fed through a discriminator for further noise reduction and audio-monitoring. A mean voltage (integrated) display was obtained by passing the original signal through a resistance-capacitance circuit (time constant 0.1 s). When a muscle-nerve fascicle had been identified, small electrode adjustments were made until a site was found in which sympathetic impulses with a good signal-to-noise ratio could be recorded. A recording of MSNA was considered acceptable when it revealed spontaneous, pulse-synchronous bursts of neural activity that fulfilled the criteria for MSNA (Sundlöf & Wallin, 1977). During the experiment, records of neural activity and ECG were monitored on a storage oscilloscope. The filtered and integrated nerve signals were sampled and stored with other signals on a personal computer using a laboratory produced data acquisition system. In addition, all signals were stored on analogue tape.

Stimulation

Two types of real and one dummy stimulus were used. One real stimulus was a single electrical square wave pulse (amplitude 100-150 V, 0.2-2 ms duration) delivered via surface electrodes taped to the left middle finger. The strength of the stimulus was adjusted to be as high as possible without causing pain. The other real stimulus type was a single 1 J flash delivered from a standard EEG photo stimulator, placed approximately 10 cm in front of the eyes (Photo-Stimulator 750, Siemens-Elema, Solna, Sweden). The dummy stimulus was a trigger pulse without subsequent sensory stimulus. All real and dummy stimuli were triggered from the R wave of the ECG via a computer-based stimulus controller that delayed the trigger pulse by 0, 200, 400 and 600 ms. Pilot experiments showed that delays of 200 and 400 ms were most efficient in evoking sympathetic inhibition (cf. Macefield et al. 1998) and therefore only these two delays were used in the study. The trigger pulses were also recorded and stored in the computer and on the tape.

Procedure

After acquiring a stable recording site, resting MSNA was recorded for 5 min. Bursts were identified by inspection of the mean voltage neurogram, aided by a computer software program developed in the laboratory, and MSNA was expressed as burst incidence (bursts per 100 heart beats) and burst frequency (bursts per minute). After the rest period the subject was informed that the stimulation was about to start at the predetermined intensity. Since the aim of the experiment was to detect putative inhibitory effects on MSNA, the experimenter monitored the integrated neurogram on an oscilloscope screen and, at the start of a sequence of sympathetic bursts, initiated each stimulus by pressing a button. In each experiment two stimulation periods were made; in one the stimuli were delivered 200 ms and in the other 400 ms after the trigger pulse. The order of the delay condition was varied between experiments. Each stimulation period contained all three types of stimuli, each type given 26-30 times. The stimulus order was generated from a list of randomly generated numbers and the same order was used for all subjects. Successive stimuli (real or dummy) were separated by at least 20 s.

Analysis

Sympathetic nerve activity. Sympathetic bursts were identified and measured in the mean voltage neurogram by a custom-manufactured semi-automatic computer analysis program. The amount of activity during the rest period was expressed as burst incidence and burst frequency.

To describe the events associated with the stimulus, the following definitions were adopted (Fig. 1). The electrical stimulus was delivered in a cardiac cycle (between R waves 0 and 1) denoted cardiac interval (CI) 1. A sympathetic burst generated in the central nervous system during this cardiac interval is defined as burst 1 and will arrive at the recording electrode after a delay corresponding to the baroreflex latency (defined as the latency from the R wave of the ECG to the start of the inhibition (equal to the peak) of the appropriate burst in the mean voltage neurogram). When recording in the peroneal nerve at the fibular head, this delay is approximately 1.3 s (Fagius & Wallin, 1980). With this definition and since the duration of the average cardiac interval was shorter than the reflex delay in all subjects, burst -1 was usually contaminated by stimulus artefact (Fig. 1).

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Figure 1. Relationship between sympathetic bursts and ECG Figure 1 shows definitions and terminology for the relationship between mean voltage neurograms and ECG. Here, an electrical stimulus was delivered in cardiac interval 1 (CI 1) with a delay of 200 ms from the R wave (note stimulus artefact in mean voltage neurogram). Baroreflex latency is defined as time from R wave 1 of the ECG (R1) to the peak of burst 1 in the mean voltage neurogram (shown by the vertical dotted line), i.e. burst 1 is terminated by the afferent baroreceptor discharge induced by the systolic pressure wave (not shown) occurring in CI 2.

In the study of Macefield et al. (1998) transcranial magnetic stimulation was found to reduce amplitudes of either bursts 0 or 1 (using the present terminology). Against this background we quantified the effects of the stimulation in individual subjects on the amplitudes of bursts 0 and 1. To this end, all amplitudes of burst 0 or burst 1, respectively, from a given stimulus type and delay condition were compared with corresponding amplitudes from the dummy stimuli. To quantify data from all subjects, mean amplitudes of bursts 0 and 1 were normalised to the mean amplitude of burst -2 in each subject (which was not contaminated by the stimulus artefact), and then corresponding normalised bursts from the dummy and the real stimuli were compared for all subjects. Since the stimuli were delivered by the experimenter at the start of a series of bursts, the maximum averaged burst amplitude usually occurred at burst -2 (cf. Fig. 3).

Skin resistance changes. Counts were made of the number of skin resistance responses occurring within 2 s from a stimulus. To be included as a response, the amplitude had to exceed 5 % of the biggest spontaneous skin resistance deflection occurring during the rest period. For each type of real stimulus and delay condition, the occurrence of responses was expressed as a percentage of the total number of stimuli. The amplitude of a skin resistance response is an unreliable measure of the strength of sympathetic sudomotor activity and can be used only if the level of activity remains constant during the measurement period (Kunimoto et al. 1992). Since in the present study sudomotor activity was highly variable and habituated during the experiment (see Results), no amplitude measurements were made.

Statistics

Data are given as means ± S.E.M. The significance of sympathetic burst amplitude reductions in individual subjects was tested with Student's unpaired t tests, whereas group comparisons were made with paired t tests. When appropriate, Bonferroni corrections for multiple comparisons were made using a nominal level of significance at P = 0.05.

	RESULTS

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Resting levels of MSNA were fairly high: 70 ± 5 (range 37-97) bursts (100 heart beats)^-1 and 45 ± 4 bursts min^-1 (range 26-67), presumably an effect of subjects being in the sitting position. Heart rate was 65 ± 2 (range 48-86) beats min^-1. Subjects in the higher age range had significantly higher levels of MSNA at rest than subjects in the lower range (83 ± 5 vs. 55 ± 5 bursts (100 heart beats)^-1 and 52 ± 4 vs. 36 ± 3 bursts min^-1, P < 0.01 for both) whereas heart rate showed no significant difference (64 ± 4 beats min^-1 in the younger and 62 ± 2 beats min^-1 in the older group).

Stimulation-induced effects on muscle sympathetic activity

Electrical stimuli. On a group basis electrical skin stimulation caused a significant reduction of the averaged mean voltage amplitude of burst 0 (delay 200 ms) and burst 1 (delay 400 ms) (Fig. 2, Table 1). When comparing the younger and older age groups findings were similar in both and there was not a clear relationship to the level of resting activity.

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Figure 2. Group effects of electrical stimuli on MSNA Average changes (means ± S.E.M.) in all subjects (n = 19) of normalised burst amplitude induced by electrical stimuli delivered after delays of 200 (upper tracings) and 400 ms (lower tracings) after the R wave of the ECG. Stimulation induced effects shown by continuous lines and . Control data depicted by dashed lines and . Asterisks indicate P values from paired t tests with Bonferroni correction regarding bursts 0 and 1. ** P < 0.01, * P < 0.05.

On an individual basis, there was a significant reduction of the mean voltage amplitude of either burst 0 or 1 (or both) in 15 of the 19 subjects (Table 2). Due to the normal variability of occurrence of sympathetic bursts, the effect could be illustrated only in averaged records. Figure 3A shows superimposed averaged records (dummy and electrical stimulation) of sympathetic activity and skin resistance from one subject (delay 200 ms). When the stimulus delay relative to the R wave of the ECG was 200 ms, the burst amplitude reduction occurred in 11 subjects, in burst 0 (six subjects), burst 1 (three subjects) or both (two subjects). When the stimulus delay was 400 ms, the reduction also occurred in 11 subjects: burst 0 was affected in one subject, burst 1 in nine cases and both bursts in one subject. In seven subjects burst amplitude reductions occurred both at stimulus delays of 200 and 400 ms whereas in eight subjects they occurred only at one of the delays. The degree of amplitude reduction (compared to the corresponding dummy burst) was similar for both delays (200 ms: 67 ± 5 %, range 38-94 %; 400 ms: 66 ± 4 %, range 44-89 %). There was no evidence for habituation of the MSNA inhibition: the attenuation of burst amplitude was similar in the first- and the second-half of each stimulation period and similarly, there was no tendency for the sympathetic inhibition to be more common in the first stimulation period than in the second.

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Figure 3. Effects of sensory stimuli on MSNA and skin resistance in one subject Examples of the inhibitory effect of electrical (A) and visual (B) stimuli on averaged mean voltage neurograms of MSNA (upper traces) and skin resistance response. In this subject both stimuli attenuated burst 1 (the second burst after the stimulus). Arrows indicate delivery of stimuli.

Visual stimuli. On a group basis there was a significant sympathetic burst amplitude reduction to visual stimuli only at a delay of 400 ms (Fig. 4, Table 1).

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Figure 4. Group effects of visual stimuli on MSNA Average changes (means ± S.E.M.) in all subjects (n = 19) of normalised burst amplitude induced by visual stimuli at stimulus delays of 200 (upper traces) and 400 ms (lower traces) after the R wave of the ECG. Symbols as in Fig. 2.

On an individual basis, visual stimuli led to significant burst amplitude reductions in eight subjects, seven of whom also responded to electrical stimuli (Table 2). An example of averaged sympathetic and skin resistance records is shown in Fig. 3B. At a stimulus delay of 200 ms the effect was present in four subjects: burst 0 was affected in one subject and burst 1 in three subjects. When the delay was 400 ms burst 1 was reduced in amplitude in five subjects. In one subject burst amplitude reductions occurred both at stimulus delays of 200 and 400 ms, whereas in seven subjects they occurred only at one of the delays. The degree of amplitude reduction (compared to the corresponding dummy burst) was similar for both delays (200 ms: 44 ± 4 %, range 36-54 %; 400 ms: 54 ± 6 %, range 35-86 %).

Comparison of effects of electrical and visual stimuli. Three subjects (one female, two males, ages 24, 65 and 70 years, respectively) differed from all others in that they responded neither to electrical nor to visual stimuli. When comparing the quantitative effects of electrical and visual stimuli, the relative burst amplitude reduction evoked by visual stimuli was usually smaller than that evoked by electrical stimuli (P = 0.05 when both delays were included in the comparison).

Stimulation-induced effects on skin resistance

Electrical and visual stimuli evoked transient skin resistance responses in all subjects, which usually were clearly seen in the averaged records (Fig. 3). There were, however, large interindividual variations in the number of responses and in three subjects skin resistance responses did not occur in all periods. Furthermore, the incidence of sympathetic skin responses was significantly greater in the first than in the second stimulation period both for electrical and visual stimuli (P < 0.05 for both). When comparing the incidence of skin resistance responses in all stimulation periods in all subjects (without taking the amplitude of the response or the order of stimulation into account), responses were significantly more common (P < 0.001) after electrical (68 ± 6 %) than after visual (30 ± 3 %) stimuli (Fig. 5). Also the averaged skin resistance amplitude was almost always higher after electrical than after visual stimulation.

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Figure 5. Comparison of skin resistance responses to electrical and visual stimuli Comparison of the occurrence of skin resistance responses to electrical (abscissa) and visual (ordinate) stimuli in all subjects. Each data point shows (as a percentage) the number of stimuli associated with a response in one stimulation sequence.

There was no difference in the occurrence of skin resistance responses between subjects with and without inhibition of muscle sympathetic activity (electrical stimuli: range of occurrence 0-100 % in both groups; visual stimuli: range of occurrence 3-77 % in subjects with neural inhibition and 0-63 % in subjects without neural inhibition).

Stimulation-induced EMG effects

EMG recordings from one deltoid muscle were made in 14 subjects. In 11 subjects 3-39 % (mean 9 %) of the individual electrical stimuli were followed (after a latency of 50-90 ms) by a short lasting burst of EMG activity. In contrast, no EMG discharges were ever seen after visual stimuli. When bursts occurred they were significantly more common in the first compared to the second stimulation period (P = 0.02). There was no significant difference in occurrence between subjects who responded and those who did not respond with MSNA inhibition (P > 0.10).

	DISCUSSION

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The main findings in the present study were: (1) a single cutaneous or visual stimulus may attenuate one or sometimes two sympathetic vasoconstrictor bursts in human muscle nerves while at the same time (judging from skin electrical resistance responses) sympathetic sudomotor fibres are activated and (2) the inhibitory effect on muscle sympathetic activity is not seen in all subjects.

Muscle sympathetic responses

On a group basis we found that a stimulus delivered 200 ms after the R wave of the ECG attenuated the amplitude of burst 0, whereas burst 1 was affected when the delay was 400 ms. In principle, electrical and visual stimuli had similar effects, but at a delay of 200 ms the inhibition evoked by visual stimuli did not reach statistical significance.

Also on an individual basis significant inhibitions were more common to electrical (15/19 subjects) than to visual (8/19 subjects) stimuli and, with only one exception, all subjects who responded to visual also responded to electrical stimuli. Three subjects responded neither to electrical nor to visual stimuli, whereas the subject with the most marked responses had inhibitory effects of 86-94 % compared to the respective control bursts in three of the four stimulation and delay conditions. This suggests that there are marked interindividual differences in the tendency to respond with inhibition of MSNA to peripheral sensory stimuli.

The finding that stimuli delivered with a delay of 200 ms from the R wave of the ECG preferentially attenuated burst 0 whereas a delay of 400 ms usually affected burst 1 is compatible with a mechanism by which stimulus-induced inhibitory effects in some way add to the inhibitory effects of the arterial baroreceptor input (cf. Macefield et al. 1998). As can be deduced from Fig. 1, burst 1 is terminated by the inhibitory effect of the systolic pressure wave of CI 2, and in a corresponding way burst 0 is terminated by the systolic pressure wave of CI 1. It may then seem surprising that a stimulus delivered in cardiac interval 1 could affect burst 0. However, as discussed previously (Fagius & Wallin, 1980), the afferent baroreceptor volley reaches the brainstem after a delay of up to 150 ms from the R wave of the ECG. With a central synaptic delay of several hundred milliseconds in the baroreflex pathway it seems reasonable that a stimulus delivered 200 ms after R wave 1 may interfere with the central processing of either burst 0 or burst 1 (or both). If the delay is longer (e.g. 400 ms) the likelihood increases that only burst 1 will be affected. The variables determining whether burst 0 or 1 will be attenuated are not known, but one factor may be beat-to-beat variations of cardiac interval.

Skin resistance responses

Electrical skin resistance responses evoked by stimuli are usually considered to be part of an arousal reaction and the stronger and more surprising the stimulus is, the higher the incidence of such responses. In addition, such responses tend to adapt and disappear with repetition. We found that skin resistance responses were more common after electrical than after visual stimuli, i.e. electrical stimuli induced stronger arousal than visual stimuli (which agreed with the subjective experience of the subjects). Furthermore, the frequency of occurrences of skin resistance responses (and EMG discharges) was significantly higher in the first than in the second stimulus period, suggesting that the degree of arousal became reduced during the course of the experiment.

Underlying mechanisms

In view of the fact that MSNA inhibition was evoked by either of two sensory stimuli, activating different cortex areas, the effect is most likely to be due to arousal. This possibility is strengthened by the finding that signs of arousal, i.e. skin resistance reductions, were most common after electrical stimuli which evoked the most pronounced inhibition of MSNA. On the other hand, there was no difference in the frequency of occurrences of skin resistance responses between subjects with and without inhibition of muscle sympathetic activity. Furthermore, the MSNA inhibition did not show signs of habituation in the same way as did the skin resistance reductions; both these findings might be seen as evidence against the arousal alternative. Arousal is, however, a complex mechanism and in animal experiments five arousal-associated neuronal populations have been described in the central nervous system (Marrocco et al. 1994). Thus, the possibility exists that the MSNA inhibition and the skin resistance responses reflect two different arousal components.

Several pieces of evidence indicate that arousal may have different effects on MSNA depending on the situation. In subjects with complete spinal cord injury a skin stimulus below the level of the lesion induces an MSNA discharge (Stjernberg et al. 1986), i.e. evokes an excitatory spinal sympathetic reflex in muscle nerves. Normally, this reflex seems to be suppressed by influence from arterial and/or cardiopulmonary baroreceptors since, during temporary baroreceptor deafferentation, arousing sensory stimuli evoke excitatory reflex responses in MSNA (Fagius et al. 1985). Furthermore, during a state of reduced consciousness or attention (stage 2 sleep) arousal-related phenomena (spontaneous or induced K-complexes in the EEG) are associated with MSNA discharges (Hornyak et al. 1991; Okada et al. 1991; Xie et al. 1999). In the present experiments, the state of the subjects was the opposite to sleep: their attention was high and focused on forthcoming sensory stimuli that arrived at irregular intervals. Taken together these findings suggest that the responsiveness to arousal in MSNA is determined both by the strength of the baroreceptor input and by the general level of consciousness or attention: during weak baroreceptor input and/or low level of attention arousal is associated with bursts of MSNA, whereas during strong baroreceptor inputs and/or high levels of consciousness or attention arousal has inhibitory effects on MSNA. The mechanism behind the K-complex-associated bursts during sleep is unclear, they may be regarded as excitatory responses to arousal or alternatively, they may be spontaneous bursts that are prominent because arousal induced MSNA inhibition is minimal.

In addition to evoking autonomic and motor effects, arousal is known to influence respiration and since there is evidence suggesting that MSNA may be inhibited from pulmonary or chest wall receptors (Seals et al. 1990; Macefield & Wallin, 1995), the possibility exists that arousal-induced respiratory effects may contribute to the MSNA response. Arousal may influence both ongoing and subsequent breaths (Johnson & Lubin, 1967; Badr et al. 1997) but, since the reduction of MSNA lasts less than 2 s, only alterations of an ongoing breath can be relevant for the present findings. An arousal stimulus may interrupt or prolong the ongoing breath, but it is unclear whether this applies to all phases of the respiratory cycle and what the effects are on MSNA.

Although the main effect of afferent baroreceptor traffic is thought to be on sympathetic and vagal neural activities, the baroreceptor input also has inhibitory effects on spinal somatic sensory pathways (Garsik et al. 1983), the Achilles tendon reflex (Dworkin et al. 1994) and pain perception (Dworkin et al. 1979, 1994). It is unclear whether these baroreceptor-induced effects will also be potentiated by surprising sensory stimuli, as found in the present study for the inhibition of MSNA.

In the study by Macefield et al. (1998) the MSNA inhibition following motor cortex activation had similar characteristics as the inhibition evoked by peripheral sensory stimuli in the present study. This does not necessarily mean that the underlying mechanism is the same. For example, Silber et al. (2000) recently concluded that although single bursts of skin sympathetic activity could be evoked both by arousal and transcranial magnetic stimulation of the motor cortex, the underlying mechanisms were different. On the other hand, in the present study many peripheral electrical stimuli led to bursts of EMG in the deltoid muscle after a latency that is compatible with a reflex loop via the motor cortex (Palmer & Ashby, 1992), and therefore, one may speculate that motor cortex activation was the reason for the MSNA inhibition in our experiments also. Arguments against this alternative are: (a) visual stimuli never evoked EMG activity in the deltoid muscle, (b) EMG activation evoked by electrical stimuli was significantly less common in the second stimulation period, which was not the case for the MSNA inhibition, (c) a long latency EMG activation need not engage the motor cortex, as it may be initiated in the brain stem, and (d) recent evidence suggests that the motor cortex excitability is transiently suppressed by an unexpected sensory stimulus (Furubayashi et al. 2000). Furthermore, although there is evidence that under some conditions central motor command may influence MSNA (Victor et al. 1995), the reported effect is an increase in activity which is contrary to the inhibition found here. In view of these findings, it seems unlikely that motor cortex activation is causing the MSNA inhibition. On the other hand, EMG was recorded from only one muscle and, therefore, this alternative cannot be completely ruled out.

In summary, brief somato-sensory or visual stimuli, delivered 200 or 400 ms after the R wave of the ECG, attenuate one or two bursts of MSNA in some, but not all healthy subjects. The inhibition is suggested to be an arousal effect.

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Top Abstract Introduction Methods Results Discussion References

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Acknowledgements

We thank Göran Pegenius for excellent technical assistance. Supported by Swedish Medical Research Council Grants nos 3546 and 12170. V.D. was supported by the Foundation Blanceflor Boncompagni-Ludovisi, née Bildt.

Authors' present addresses

V. Donadio: Department of Neurological Science, Unit of Clinical Neurophysiology, University of Bologna, Italy.

M. Kallio: Department of Clinical Neurophysiology, University of Oulu, Finland.

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