Physiological and pathophysiological firing properties of single postganglionic sympathetic neurons in humans.

It has long been known from microneurographic recordings in human subjects that the activity of postganglionic sympathetic axons occurs as spontaneous bursts, with muscle sympathetic nerve activity (MSNA) exhibiting strong cardiac rhythmicity via the baroreflex and skin sympathetic nerve activity showing much weaker cardiac modulation. Here we review the firing properties of single sympathetic neurons, obtained using highly selective microelectrodes. Individual vasoconstrictor neurons supplying muscle or skin, or sudomotor neurons supplying sweat glands, always discharge with a low firing probability (~30%) and at very low frequencies (~0.5 Hz). Moreover, they usually fire only once per cardiac interval but can fire greater than four times within a burst. Modeling has shown that this pattern can best be explained by individual neurons being driven by, on average, two preganglionic inputs. Unitary recordings of muscle vasoconstrictor neurons have been made in several pathophysiological states, including heart failure, hypertension, obstructive sleep apnea, bronchiectasis, chronic obstructive pulmonary disease, depression, and panic disorder. The augmented MSNA in each of these diseases features an increase in firing probability and discharge frequency of individual muscle vasoconstrictor neurons above that seen in healthy subjects, yet firing rates rarely exceed 1 Hz. However, unlike patients with heart failure, all patients with respiratory disease or panic disorder, and patients with hyperhidrosis, exhibited an increase in multiple within-burst firing, which emphasizes the different modes by which the sympathetic nervous system grades its output in pathophysiological states of high sympathetic nerve activity.

Recording sympathetic nerve activity in conscious humans and other mammals: guidelines and the road to standardization.

Over the past several decades, studies of the sympathetic nervous system in humans, sheep, rabbits, rats, and mice have substantially increased mechanistic understanding of cardiovascular function and dysfunction. Recently, interest in sympathetic neural mechanisms contributing to blood pressure control has grown, in part because of the development of devices or surgical procedures that treat hypertension by manipulating sympathetic outflow. Studies in animal models have provided important insights into physiological and pathophysiological mechanisms that are not accessible in human studies. Across species and among laboratories, various approaches have been developed to record, quantify, analyze, and interpret sympathetic nerve activity (SNA). In general, SNA demonstrates "bursting" behavior, where groups of action potentials are synchronized and linked to the cardiac cycle via the arterial baroreflex. In humans, it is common to quantify SNA as bursts per minute or bursts per 100 heart beats. This type of quantification can be done in other species but is only commonly reported in sheep, which have heart rates similar to humans. In rabbits, rats, and mice, SNA is often recorded relative to a maximal level elicited in the laboratory to control for differences in electrode position among animals or on different study days. SNA in humans can also be presented as total activity, where normalization to the largest burst is a common approach. The goal of the present paper is to put together a summary of "best practices" in several of the most common experimental models and to discuss opportunities and challenges relative to the optimal measurement of SNA across species.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/guidelines-for-measuring-sympathetic-nerve-activity/.

Neural control of blood pressure in women: differences according to age.

PURPOSE: The blood pressure "error signal" represents the difference between an individual's mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the "T50"). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause. METHODS: We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25 ± 1 years) and 12 postmenopausal women (61 ± 2 years) before and during complete autonomic blockade with trimethaphan camsylate. RESULTS: At baseline, young women had a negative error signal (-8 ± 1 versus 2 ± 1 mmHg, p < 0.001; respectively) and lower muscle sympathetic nerve activity (15 ± 1 versus 33 ± 3 bursts/min, p < 0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r = -0.725, p = 0.008) but not in young women (r = -0.337, p = 0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r = 0.886, p < 0.001; older: r = 0.870, p < 0.001). CONCLUSIONS: Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women.

Sex differences and blood pressure regulation in humans.

NEW FINDINGS: What is the topic of this review? Over the past decade, our team has investigated interindividual variability in human blood pressure regulation. What advances does it highlight? In men, we have found a tight relationship between indices of sympathetic activity and vascular resistance across the age span. This relationship is absent in young women but seen in postmenopausal women. These sex and age differences in vascular resistance are largely a result of changes in the balance of vasodilating and vasoconstricting adrenergic receptor tone. When these changes are considered along with cardiac output, a coherent picture is beginning to emerge of why blood pressure rises more with age in women than men. Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12 years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because ß-adrenergic vasodilator mechanisms offset α-adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, ß-adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age-related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups.

Sympathetic nerve activity and peripheral vasodilator capacity in young and older men.

Interindividual variability in sympathetic nerve activity (SNA) has provided insight into integrative mechanisms contributing to blood pressure (BP) regulation in humans. In young people, the influence of high SNA on BP is balanced by lower cardiac output and less adrenergic vasoconstrictor responsiveness. Older people have higher SNA and higher BP. We hypothesized that SNA has a restraining effect on peripheral vasodilator responsiveness in young and older men, such that individuals with higher tonic SNA would show less forearm vasodilatation to exogenous vasodilators. We measured muscle SNA (MSNA; microneurography) and forearm vasodilator responses to intra-arterial infusions of acetylcholine (ACh; endothelium dependent) and sodium nitroprusside (SNP; endothelium independent) in 13 young (age; 27 ± 1 yr) and 16 older (61 ± 2 yr) men. Forearm vascular conductance (FVC) responses to ACh were lower in the older men at the two highest doses (2 and 4 µg·100 ml(-1)·min(-1); Δ395 ± 81 vs. 592 ± 87% and 412 ± 87 vs. 616 ± 132%, P < 0.05), and MSNA was higher (64 ± 4 vs. 41 ± 2 bursts/100 hb; P < 0.05). There was no difference in the FVC response to SNP between young and older men (P > 0.05). In young men, there was an inverse relationship between resting MSNA and FVC responses (%change) to both ACh and SNP (r = -0.83 and r = -0.83, respectively; P < 0.05). In older men, however, this relationship was not observed. Tonic SNA may act to restrain vasodilator responses in young men, whereas in older men a lack of such restraint may be protective against the pressor effects of higher SNA.

Viscerosympathetic reflexes in human spinal cord injury: relationships between detrusor pressure, blood pressure and skin blood flow during bladder distension.

Autonomic dysreflexia, a dangerous and sustained increase in blood pressure brought about by widespread, reflexly generated vasoconstriction, can be induced by visceral or somatic sensory inputs originating below the lesion following spinal cord injury (SCI). We assessed whether cutaneous vasoconstriction below the lesion could serve as a proxy marker of incipient autonomic dysreflexia during bladder distension. Skin blood flow (pulse plethysmography), sweat release, blood pressure, heart rate, bladder and rectal pressures were recorded during routine cystometry (urodynamics) in 16 patients with SCI. Eight urological patients without SCI served as control subjects. In all SCI patients, who had sustained injuries 2 months to 44 years previously at levels C3-T3, bladder filling (mean ± SD, 339 ± 132 ml) induced increases in detrusor (bladder-rectal) pressure (52 ± 25 cmH(2)O) and cutaneous vasoconstriction in the fingers, but no consistent increases in sweat release. This occurred irrespective of whether the spinal lesions were complete [American Spinal Injury Association (ASIA) grade A, n = 6] or incomplete (ASIA B-D; n = 10). Group mean blood pressure for the SCI patients increased by 17 ± 15 mmHg, but in four patients the pressure decreased or did not change. Despite similar bladder volumes (423 ± 126 ml) in the control patients, the increases in detrusor pressure (14 ± 8 cmH(2)O) and blood pressure (9 ± 12 mmHg) were significantly smaller than in the SCI patients; moreover, there were no consistent changes in skin blood flow in the control subjects. In all SCI patients, changes in finger pulse amplitudes were inversely correlated to changes in detrusor pressure (mean r = -0.62 ± 0.17). Changes in finger pulse amplitudes correlated inversely to changes in blood pressure in nine of 15 patients. It is concluded that cystometry in SCI patients is associated with detrusor and cardiovascular reflex effects that are exaggerated compared with those in intact subjects and that measurement of skin blood flow from the fingers in patients with a high spinal lesion provides a supplementary, clinically useful, non-invasive and continuous marker of spinally mediated viscerosympathetic reflex activity below the lesion in such patients.

From MEG to clinical EEG: evaluating a promising non-invasive estimator of defense-related muscle sympathetic nerve inhibition.

Sudden, unexpected stimuli can induce a transient inhibition of sympathetic vasoconstriction to skeletal muscle, indicating a link to defense reactions. This phenomenon is relatively stable within, but differs between, individuals. It correlates with blood pressure reactivity which is associated with cardiovascular risk. Inhibition of muscle sympathetic nerve activity (MSNA) is currently characterized through invasive microneurography in peripheral nerves. We recently reported that brain neural oscillatory power in the beta spectrum (beta rebound) recorded with magnetoencephalography (MEG) correlated closely with stimulus-induced MSNA inhibition. Aiming for a clinically more available surrogate variable reflecting MSNA inhibition, we investigated whether a similar approach with electroencephalography (EEG) can accurately gauge stimulus-induced beta rebound. We found that beta rebound shows similar tendencies to correlate with MSNA inhibition, but these EEG data lack the robustness of previous MEG results, although a correlation in the low beta band (13-20 Hz) to MSNA inhibition was found (p = 0.021). The predictive power is summarized in a receiver-operating-characteristics curve. The optimum threshold yielded sensitivity and false-positive rate of 0.74 and 0.33 respectively. A plausible confounder is myogenic noise. A more complicated experimental and/or analysis approach is required for differentiating MSNA-inhibitors from non-inhibitors based on EEG, as compared to MEG.

Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors.

Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7- to 10-fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA-TPR relationship. Recent evidence suggests that ß-adrenergic vasodilatation offsets the vasoconstrictor effects of α-adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective ß-adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women.

Brain structural and functional correlates to defense-related inhibition of muscle sympathetic nerve activity in man.

An individual's blood pressure (BP) reactivity to stress is linked to increased risk of hypertension and cardiovascular disease. However, inter- and intra-individual BP variability makes understanding the coupling between stress, BP reactivity, and long-term outcomes challenging. Previous microneurographic studies of sympathetic signaling to muscle vasculature (i.e. muscle sympathetic nerve activity, MSNA) have established a neural predictor for an individual's BP reactivity during short-lasting stress. Unfortunately, this method is invasive, technically demanding, and time-consuming and thus not optimal for widespread use. Potential central nervous system correlates have not been investigated. We used MagnetoEncephaloGraphy and Magnetic Resonance Imaging to search for neural correlates to sympathetic response profiles within the central autonomic network and sensorimotor (Rolandic) regions in 20 healthy young males. The main correlates include (a) Rolandic beta rebound and an anterior cingulate cortex (ACC) response elicited by sudden stimulation and (b) cortical thickness in the ACC. Our findings highlight the involvement of the ACC in reactions to stress entailing peripheral sympathetic responses to environmental stimuli. The Rolandic response furthermore indicates a surprisingly strong link between somatosensory and autonomic processes. Our results thus demonstrate the potential in using non-invasive neuroimaging-based measures of stress-related MSNA reactions, previously assessed only using invasive microneurography.

Hysteresis in the sympathetic baroreflex: role of baseline nerve activity.

Sympathetic baroreflex sensitivity (BRS) is greater during decreasing compared to increasing diastolic blood pressure (DBP) in young men and women. In older men and women there is no difference in sympathetic BRS to increasing and decreasing DBP. We investigated whether the sensitivity of the central nervous system to increasing and decreasing DBP is dependent upon baseline muscle sympathetic nerve activity (MSNA). We hypothesised that the difference in sympathetic BRS between falling and rising segments of DBP would be positively related to baseline MSNA in 30 young men, 21 young women, 14 older men and 14 postmenopausal women. MSNA was measured using peroneal microneurography and BRS was measured using the spontaneous baroreflex threshold technique. On average, sympathetic BRS was greater during decreasing compared to increasing DBP in young men (P <0.05) and women (P <0.05). In older men and women, mean sympathetic BRS was similar in response to increasing and decreasing DBP. The difference (delta) between the falling and rising BRS correlated with baseline MSNA in young (r =0.58, P <0.05) and older men (r =0.66, P <0.05) and postmenopausal women (r =0.74, P <0.05). Thus, all men, and older women, with higher BRS to falling DBP had lower baseline MSNA. This relationship was not observed in young women (r =0.14, P >0.05). In summary, baseline MSNA plays a role in determining sympathetic BRS to falling and rising DBP in young and older men and postmenopausal women, but not in young women. This relationship is consistent with a decreased potential for sympathoexcitation in people with higher resting MSNA. Furthermore, the lack of relationship in young women suggests important contributions of sex hormones to differential responses of MSNA to falling and rising pressures.

Sex and ageing differences in resting arterial pressure regulation: the role of the ß-adrenergic receptors.

In men, muscle sympathetic nerve activity (MSNA) is positively related to total peripheral resistance (TPR) and inversely related to cardiac output (CO). However, this relationship was not observed in young women. We aimed to investigate whether simultaneous ß-adrenergic stimulation offsets this balance in young women. Furthermore, we aimed to examine whether the ability of the ß-adrenergic receptors to offset the transduction of MSNA into vasoconstrictor tone was lost in postmenopausal women. We measured MSNA (peroneal microneurography), arterial pressure (brachial line), CO (Modelflow), TPR and changes in forearm vascular conductance (FVC) to increasing doses of noradrenaline (NA; 2, 4 and 8 ng (100 ml)(-1) min(-1)) before and after systemic ß-blockade with propranolol in 17 young men, 17 young women and 15 postmenopausal (PM) women. The percentage and absolute change in FVC to the last two doses of NA were greater during ß-blockade in young women (P < 0.05), whereas the change in FVC was similar before and during ß-blockade in young men and PM women (P > 0.05). Before ß-blockade there was no relationship of MSNA to TPR or mean arterial pressure (MAP) in young women. Following ß-blockade, MSNA became positively related to TPR (r = 0.59, P < 0.05) and MAP (r = 0.58, P < 0.05). In the PM women and young men, MSNA was positively associated with TPR. ß-Blockade had no effect on this relationship. Our data suggest that the ß-adrenergic receptors offset α-adrenergic vasoconstriction in young women but not young men or PM women. These findings may explain in part the tendency for blood pressure to rise after menopause in women.

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.

Baroreflex control of muscle sympathetic nerve activity: a nonpharmacological measure of baroreflex sensitivity.

The sensitivity of baroreflex control of sympathetic nerve activity (SNA) represents the responsiveness of SNA to changes in blood pressure. In a slightly different analysis, the baroreflex threshold measures the probability of whether a sympathetic burst will occur at a given diastolic blood pressure. We hypothesized that baroreflex threshold analysis could be used to estimate the sensitivity of the sympathetic baroreflex measured by the pharmacological modified Oxford test. We compared four measures of sympathetic baroreflex sensitivity in 25 young healthy participants: the "gold standard" modified Oxford analysis (nitroprusside and phenylephrine), nonbinned spontaneous baroreflex analysis, binned spontaneous baroreflex analysis, and threshold analysis. The latter three were performed during a quiet baseline period before pharmacological intervention. The modified Oxford baroreflex sensitivity was significantly related to the threshold slope (r = 0.71, P < 0.05) but not to the binned (1 mmHg bins) and the nonbinned spontaneous baroreflex sensitivity (r = 0.22 and 0.36, respectively, P > 0.05), which included burst area. The threshold analysis was also performed during the modified Oxford manipulation. Interestingly, we found that the threshold analysis results were not altered by the vasoactive drugs infused for the modified Oxford. We conclude that the noninvasive threshold analysis technique can be used as an indicator of muscle SNA baroreflex sensitivity as assessed by the modified Oxford technique. Furthermore, the modified Oxford method does not appear to alter the properties of the baroreflex.

Chronic pain has a small influence and mood has no influence on vibrotactile perception thresholds among working women.

In chronic diffuse upper limb pain physical abnormalities are usually absent. The aims of our study were to investigate: (1) the function of somatosensory pathways and (2) the influence of mood on vibration perception. Measurements were made of: (i) vibrotactile perception thresholds (VPTs) and nerve conduction in working women with (n = 35) and without (n = 65) chronic diffuse upper limb pain, and (ii) perceived stress and energy using a two-dimensional mood adjective checklist. The groups did not differ in any nerve conduction measurements. Women with chronic pain had raised VPTs in the radial and ulnar nerve areas, but not in the median nerve area. Neither perceived stress nor energy appeared to influence the VPT. Increases of VPTs in chronic diffuse upper limb pain may be due to peripheral nerve affliction, but our findings support the idea that they may also be secondary to pain and may be related to a central nervous mechanism.

Sex differences in alpha-adrenergic support of blood pressure.

We tested whether the inter-individual variability in alpha-adrenergic support of blood pressure plays a critical role in the sex differences in tonic support of blood pressure by the autonomic nervous system. Blockade of the alpha-adrenergic receptors was achieved via phentolamine and showed a smaller (P < 0.05) decrease in blood pressure in women compared to men, implying that alpha-adrenergic support of blood pressure is less in women than in men.

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.

Arousal elicits exaggerated inhibition of sympathetic nerve activity in phobic syncope patients.

Alerting stimuli causing arousal have been shown to elicit a reproducible transient inhibition of muscle sympathetic nerve activity (MSNA) in healthy subjects. The aim of the present study was to test whether this inhibitory response to arousal is exaggerated in patients with a history of vasovagal syncope. We studied 24 untreated syncope patients, 12 of whom met the DSM-IV-TR diagnostic criteria for blood/injury phobia and 18 age-matched healthy subjects. MSNA was recorded from the peroneal nerve at the fibular head. Arousal was induced by randomly presented trains of five electrical pulses delivered to a finger. The pulses were triggered on five consecutive R waves of the ECG, with a delay of 200 ms. Patients also underwent cardiological and neurological examinations, tilt test and a structured interview to investigate diagnostic criteria for specific phobia. The syncope patients had significantly lower resting MSNA (29 +/- 2 bursts/min) and diastolic blood pressure (BP, 78 +/- 2 mmHg) compared to controls (36 +/- 2 bursts/min and 84 +/- 3 mmHg; P < 0.05), whereas no significant differences were found for resting heart rate and systolic BP. The phobic patient group exhibited prolonged sympathetic inhibitions to arousal stimuli compared to controls and non-phobic patients, whereas no difference was found between tilt-positive and tilt-negative patients or between controls and non-phobic patients. The findings suggest that the degree of inhibition in response to arousal stimuli is related to a subjective factor coupled to fear of blood/injury. The exaggerated inhibition in patients with phobia to blood/injury may be a factor predisposing to syncope in those patients.

Axonal changes in spinal cord injured patients distal to the site of injury.

It is generally assumed that the peripheral nervous system remains intact following a spinal injury. Accordingly, the electrical thresholds of motor axons in a peripheral nerve below the lesion should be similar to those in intact subjects. Yet in attempts to enter the common peroneal nerve with microelectrodes in 24 quadriplegic or paraplegic individuals it was often found that electrical stimulation over or within the nerve failed to elicit contractions in the pre-tibial flexors. To investigate whether consistent changes in axonal physiology occurred distal to the site of injury in patients with spinal cord injury (SCI), motor nerve excitability was formally tested in 15 of these patients. Threshold tracking techniques were used to measure axonal excitability parameters (stimulus-response curves, strength-duration properties, threshold electrotonus, a current-threshold relationship and the recovery cycle) of motor axons in the median and common peroneal nerves. In these patients motor axons were uniformly of high threshold and consequently, stimulus-response curves were shifted to the right. In some SCI patients, axons were completely inexcitable. Amplitudes of compound motor action potentials were reduced, consistent with axonal loss and strength-duration time constant was significantly reduced in SCI patients (SCI 0.13 +/- 0.02 ms, controls 0.43 +/- 0.02 ms, mean +/- SE, P < 0.0001). Excitability changes were more prominent the more clinically severe the injury, with progressive deterioration over time since the original injury. While compression and traction sustained during the original injury or subsequent hospital rehabilitation may contribute in part to some of these changes, it is difficult to attribute these findings solely to such processes. Changes in axonal structure and ion channel function, but perhaps more critically decentralization and consequent inactivity, are likely to underlie the complex changes observed in axonal excitability in SCI patients.

Assessing the integrity of sympathetic pathways in spinal cord injury.

STUDY DESIGN: Measurement of cutaneous sympathetic reflexes and hemodynamic responses to brief electrical stimuli applied above (forehead) and below (abdominal wall) a spinal lesion. OBJECTIVE: To assess the validity of using cutaneous vasoconstriction as a sensitive indicator of increases in sympathetic activity in spinal cord injury. SETTING: Prince of Wales Medical Research Institute, Australia. SUBJECTS: Twenty spinal cord injured subjects with injuries ranging from C3-T11 and nine able-bodied controls. METHOD: Cutaneous electrical stimulation was applied to the forehead and abdominal wall to subjects at unexpected times. Sudomotor and vasomotor responses, as well as continuous arterial pressure, heart rate and respiration were monitored. RESULTS: Sudomotor (electrodermal) responses to forehead stimulation were scarce in spinal cord injured subjects, whereas cutaneous vasoconstrictor responses (photoelectric pulse plethysmography) provided a sensitive indicator of any remaining central control of sympathetic function below the lesion. Electrical stimulation applied to the abdominal wall evoked vasoconstrictor reflexes below the lesion in the majority of spinal cord injured subjects, whereas only a limited number of electrodermal responses were observed. That these cutaneous vasoconstrictor responses could reflect parallel increases in muscle and splanchnic vasoconstrictor activity was indicated by the increases in blood pressure; patients lacking vasoconstrictor responses rarely showed stimulus-induced blood pressure increases. CONCLUSION: Our findings show that skin vasomotor responses to somatosensory stimulation provide a more sensitive tool than electrodermal responses for evaluation of sympathetic function below a spinal cord lesion. STATEMENT OF ETHICS: We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research, and all experiments were conducted with the understanding and consent of each subject.