B. Gunnar Wallin

Sympathetic nerve activity after acupuncture in humans

&NA; The aim of the present study was to determine if acupuncture stimulation inhibits sympathetic nerve activity in humans. Multiunit efferent postganglionic sympathetic activity was recorded with a tungsten microelectrode inserted in a muscle fascicle of the peroneal nerve. Mean arterial pressure, heart rate and skin blood flow were also monitored. Pain thresholds were measured by electrical tooth pain stimulation. After a 30 min rest, acupuncture needles were inserted bilaterally into the Li 11 and the Li 4 acupuncture points, and manipulated until ‘chi’ cramp‐like sensation was reported. Electrical stimulation (2 Hz, 0.6–0.8 ms duration, maximal tolerated stimulation without discomfort) was delivered for 30 min and the physiological recordings were continued for 90 min after the end of acupuncture. In a placebo control experiment, the same procedure was followed, except that acupuncture needles were inserted subcutaneously and no manipulation or stimulation was given. The stimulator delivered pulses to an unconnected channel, hence, the same audiovisual stimuli were experienced as with acupuncture, and care was taken to ask the same questions about sensations in the placebo and the acupuncture groups. Electroacupuncture produced an increase in pain threshold which was paralleled by a transient increase in muscle sympathetic nerve activity. During acupuncture, there was a small increase in heart rate and mean arterial pressure, but there was no post‐acupuncture hypotension. The placebo control procedure did not change pain threshold or sympathetic nerve traffic. The findings suggest that electroacupuncture produces moderate hypoalgesia in humans paralleled by a significant increase in muscle sympathetic nerve activity.

Comparison of Sympathetic Nerve Activity in Normotensive and Hypertensive Subjects

A microneurographic technique was used to record multiunit sympathetic activity in skin and muscle nerves of 24 healthy subjects and 21 hypertensive subjects. In both groups, the sympathetic activity recorded during rest appeared in bursts following one of two highly different temporal patterns—one characteristic for muscle nerves and the other characteristic for skin nerves. Muscle nerve sympathetic activity probably consisting of vasoconstrictor impulses, occurred in bursts that followed the pulse rhythm and waxed and waned in inverse relation to spontaneous blood pressure fluctuations. Transient random elevations of blood pressure above a certain level caused total suppression of the sympathetic bursts. This inhibitory blood pressure level was higher in hypertensive subjects than it was in normotensive subjects, suggesting an elevated baroreflex working range in hypertension. No other important differences in muscle nerve sympathetic activity were noted between the two groups. Skin nerve sympathetic activity, probably consisting of both vasoconstrictor and sudomotor impulses, had a similar temporal pattern in normotensive and hypertensive subjects at rest: bursts of variable duration occurred randomly or were loosely related to the respiratory rhythm. In both groups of subjects, the strength of this activity increased in response to arousal stimuli, mental stress, and body cooling. These findings emphasize the necessity of having highly standardized experimental conditions in future studies aimed at a quantitative comparison of the absolute strength of sympathetic activity in normotensive and hypertensive subjects.

Functional role of unmyelinated tactile afferents in human hairy skin: sympathetic response and perceptual localization

In addition to A-beta fibres the human hairy skin has unmyelinated (C) fibres responsive to light touch. Previous functional magnetic resonance imaging (fMRI) studies in a subject with a neuronopathy who specifically lacks A-beta afferents indicated that tactile C afferents (CT) activate insular cortex, whereas no response was seen in somatosensory areas 1 and 2. Psychophysical tests suggested that CT afferents give rise to an inconsistent perception of weak and pleasant touch. By examining two neuronopathy subjects as well as control subjects we have now demonstrated that CT stimulation can elicit a sympathetic skin response. Further, the neuronopathy subjects’ ability to localize stimuli which activate CT afferents was very poor but above chance level. The findings support the interpretation that the CT system is well suited to underpin affective rather than discriminative functions of tactile sensations.

Following One's Heart: Cardiac Rhythms Gate Central Initiation of Sympathetic Reflexes

Central nervous processing of environmental stimuli requires integration of sensory information with ongoing autonomic control of cardiovascular function. Rhythmic feedback of cardiac and baroreceptor activity contributes dynamically to homeostatic autonomic control. We examined how the processing of brief somatosensory stimuli is altered across the cardiac cycle to evoke differential changes in bodily state. Using functional magnetic resonance imaging of brain and noninvasive beat-to-beat cardiovascular monitoring, we show that stimuli presented before and during early cardiac systole elicited differential changes in neural activity within amygdala, anterior insula and pons, and engendered different effects on blood pressure. Stimulation delivered during early systole inhibited blood pressure increases. Individual differences in heart rate variability predicted magnitude of differential cardiac timing responses within periaqueductal gray, amygdala and insula. Our findings highlight integration of somatosensory and phasic baroreceptor information at cortical, limbic and brainstem levels, with relevance to mechanisms underlying pain control, hypertension and anxiety.

The Effect of Metformin and Insulin on Sympathetic Nerve Activity, Norepinephrine Spillover and Blood Pressure in Obese, Insulin Resistant, Normoglycemic, Hypertensive Men

To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance, sympathetic nerve activity and blood pressure, 6 obese insulin resistant, normoglycemic hypertensive men were investigated (age 49 +/- 2 years, BMI 27.6 +/- 1.2, mean +/- SEM). The study had a placebo controlled, double blind, cross over design with 6 weeks metformin treatment (850 mg b.i.d) vs placebo. Blood pressure was measured weekly. At the end of each treatment period, glucose infusion rate (GIR), muscle sympathetic nerve activity (MSA) and renal and total body norepinephrine (NE) kinetics (radioisotope dilution) were examined during euglycemic hyperinsulinemic clamp. Fasting insulin was 13 +/- 3 and 10 +/- 2 mU/l and fasting glucose 5.3 +/- 0.2 and 5.1 +/- 0.1 mmol/l after placebo and metformin treatment, respectively (ns). GIR during the last hour of the insulin clamp was 3.7 +/- 0.6 vs 3.6 +/- 0.6 mg/kg x min (ns). Resting MSA, total body and right renal NE spillover did not differ significantly after placebo and metformin treatment. Systolic and diastolic blood pressures were 151 +/- 10/95 +/- 5 mmHg after placebo and 146 +/- 5/94 +/- 5 mmHg after metformin treatment (ns). Thus metformin treatment did not have any significant effect on insulin sensitivity, blood pressure or sympathetic activity in this small group of patients. Renal plasma flow and MSA increased significantly during the insulin clamp, whereas renal NE and total body NE spillover remained unchanged, suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia.

Sympathetic nerve traffic correlates with the release of nitric oxide in humans: implications for blood pressure control

1 Resting human sympathetic vasoconstrictor traffic displays large reproducible inter‐individual differences which are similar in nerves to muscle, heart and kidney. In spite of this there is no correlation between levels of blood pressure and sympathetic traffic. To test the hypothesis that the pressor effect of the vasoconstrictor activity is counteracted by a circulating dilating factor we measured muscle nerve sympathetic activity (MSA) and an indicator of nitric oxide release (plasma nitrate) in healthy young males. 2 Sympathetic activity was recorded with the microneurographic technique in the peroneal nerve and a forearm venous plasma sample was obtained in twenty‐one normotensive males aged 21–28 years. Plasma nitrate was analysed by gas chromatography and mass spectrometry. 3 There was a positive linear correlation between the plasma nitrate concentration and the strength of MSA both when the nerve activity was expressed as bursts per minute and bursts per 100 heart beats (r= 0.51, P= 0.02 and r= 0.46, P= 0.04, respectively). 4 The data suggest that the stronger the sympathetic activity the higher the release of the dilating substance, nitric oxide. This would be expected to counteract vasoconstrictor effects of the nerve traffic and thereby contribute to the lack of relationship between resting levels of MSA and blood pressure. We speculate that altered coupling between sympathetic traffic and nitric oxide release may cause abnormal peripheral resistance, e.g. in hypertension.

Autonomic and Thermal Sensory Symptoms and Dysfunction After Stroke

BACKGROUND AND PURPOSEnSymptoms interpreted as unilateral disturbances of autonomic function, such as coldness, dryness, sweating, and trophic changes, are well known but incompletely understood clinical problems after stroke. The present study provides data related to the incidence and mechanisms behind such symptoms.nnnMETHODSnTemperature perception thresholds, skin temperatures, evaporation rates, and skin blood flow responses were measured bilaterally in 37 stroke patients aged 58 +/- 13 years (mean +/- SD) and in a control group of 15 patients aged 64 +/- 15 years with a single transient ischemic attack.nnnRESULTSnOf the 37 stroke patients, 43% reported a sensation of coldness in the contralesional side of the body. Basal skin blood flow and temperature were relatively lower in the contralesional side. There was an excess of evaporation in the contralesional side after brain stem lesions and in the ipsilesional side after hemispheric lesions. Vasomotor reflex asymmetries occurred in 34% of the patients and were due to weak vasodilator or vasoconstrictor reflexes in the ipsilesional side. These abnormalities correlated significantly to sensations of unilateral coldness, hypalgesia, and thermohypesthesia in the contralesional side and anatomically to lesions in spinothalamo-cortical pathways.nnnCONCLUSIONSnFocal central nervous system lesions due to stroke may result in symptoms and measurable evidence of unilateral disturbance of skin sympathetic function. Vasomotor asymmetries are probably due to lesions of vasomotor pathways descending uncrossed. Subjective coldness may be due to disturbed central processing.

Resting discharge of human muscle spindles is not modulated by increases in sympathetic drive

There is evidence in experimental animals that, in addition to receiving fusimotor drive, muscle spindles are subject to modulation by the sympathetic nervous system. We examined the validity of this idea in human subjects by recording from muscle spindles in the relaxed ankle and toe extensor muscles during a strong and sustained physiological activation of muscle sympathetic outflow. Unitary recordings were made from 20 primary and 17 secondary muscle spindle afferents via a tungsten microelectrode inserted percutaneously into the peroneal nerve in 10 awake, healthy subjects seated with the legs supported in the extended position. ECG, blood pressure, respiration and calf circumference were also recorded. The majority of the muscle spindles were spontaneously active at rest; a background discharge was induced in four silent spindles by vibrating the tendon. A sustained increase in muscle vasoconstrictor activity, an increase in calf volume and a fall in pulse pressure were produced by subjects performing a 30‐40 s maximal inspiratory breath‐hold. Despite this strong increase in muscle sympathetic outflow no significant changes occurred in the discharge of either primary or secondary muscle spindle afferents, measured as a change in mean frequency and variability over sequential 5 s epochs and compared with the preceding period of rest. Strong chemoreceptor‐driven sympathetic bursts during sustained expiratory breath‐holds also failed to modulate the firing of 14 spindle endings. We conclude that a sustained, physiological increase in muscle sympathetic activity causes no detectable change in muscle spindle firing, lending no support to the concept that the sympathetic nervous system can influence the sensitivity of human muscle spindles directly.

Inhibition of muscle sympathetic outflow following transcranial cortical stimulation

The possible contribution of cerebral cortical activity to sympathetic outflow to the muscle vascular bed was assessed in normal human subjects. Muscle sympathetic activity was recorded from motor fascicles of the peroneal nerve in 8 subjects while transcranial magnetic stimulation was applied over the vertex, or unilaterally over the hand area of cortex. By triggering the cortical stimulus from the R-wave of the ECG and introducing delays of 0-600 ms between the trigger and the stimulus, we found that a single cortical stimulus delayed by 200-400 ms caused a pronounced inhibition of one pulse-synchronous sympathetic burst. Stimulation over the vertex was more effective than stimulation over the hand area of cortex. In addition to this inhibition of muscle sympathetic outflow, brain stimulation caused an increase in cutaneous sympathetic activity, both sudomotor (sweating) and vasoconstrictor (decrease in skin blood flow). We suggest that the cerebral cortex may normally suppress muscle sympathetic outflow and speculate that lesions that interrupt this source of inhibition (such as those caused by stroke) may result in an augmented muscle sympathetic outflow.

Bicycle ergometer test to obtain adequate skin temperature when measuring nerve conduction velocity

OBJECTIVEnTo achieve optimal diagnostic accuracy, measurements of nerve conduction velocity require standardised tissue temperatures. To warm an extremity to a desired temperature that remains constant during the measurement may be difficult, especially in subjects with low finger temperatures. The aim of this study was to investigate if a submaximal bicycle ergometer test before the examination would be a useful method of obtaining high and stable finger temperatures during nerve conduction studies in the hand.nnnMETHODSn114 women aged 25-65 (median 44) performed a bicycle ergometer test on an electrically braked bicycle ergometer (Siemens-Elema) before they underwent a nerve conduction test.nnnRESULTSnBefore cycling, the mean finger temperature was 28.1 degrees C (range 20.5-35.4 degrees C) and 15 min after the test 35.1 degrees C (range 30.3-36.9 degrees C). The levels remained almost constant throughout the nerve conduction examination, which had a duration of approximately 25 min.nnnCONCLUSIONSnA bicycle ergometer test proved to be a simple and effective method of raising hand temperature.