It is known that the sudden increases in blood pressure associated with autonomic dysreflexia in people with spinal cord injury (SCI) are due to a spinally mediated reflex activation of sympathetic vasoconstrictor neurons supplying skeletal muscle and the gut. Apart from visceral inputs, such as those originating from a distended bladder, there is a prevailing opinion that autonomic dysreflexia can be triggered by noxious stimulation below the lesion. However, do noxious inputs really cause an increase in blood pressure in SCI? Using microelectrodes inserted into a peripheral nerve to record sympathetic nerve activity we had previously shown that selective stimulation of small-diameter afferents in muscle or skin, induced by bolus injection of hypertonic saline into the tibialis anterior muscle or the overlying skin, evokes a sustained increase in muscle sympathetic nerve activity and blood pressure and a transient increase in skin sympathetic nerve activity and decrease in skin blood flow in able-bodied subjects. We postulated that these sympathetic responses would be exaggerated in SCI, with a purely noxious stimulus causing long-lasting increases in blood pressure and long-lasting decreases in skin blood flow. Surprisingly, though, we found that intramuscular or subcutaneous injection of hypertonic saline into the leg caused negligible changes in these parameters. Conversely, weak electrical stimulation over the abdominal wall, which in able-bodied subjects is not painful and activates large-diameter cutaneous afferents, caused a marked increase in blood pressure in SCI but not in able-bodied subjects. This suggests that it is activation of large-diameter somatic afferents, not small-diameter afferents, that triggers increases in sympathetic outflow in SCI. Whether the responses to activation of large-diameter afferents reflect plastic changes in the spinal cord in SCI is unknown.

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA – but not COPD or BE – the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an increase in firing probability and mean firing rates of individual neurons. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD, and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasize the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurons and recruitment of additional neurons being the dominant mechanisms.

Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor, or sudomotor neurons, discharge with a low firing probability (∼30%), generate low firing rates (∼0.5 Hz) and typically fire only once per cardiac interval. The purpose of the present study was to use modeling of spike trains in an attempt to define the number of preganglionic neurons that drive an individual postganglionic neuron. Artificial spike trains were generated in 1–3 preganglionic neurons converging onto a single postganglionic neuron. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500, or 3000 ms and the SD varied between 0.5×, 1.0×, and 2.0× the mean interval; the discharge frequency of each preganglionic neuron exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neuron could only be explained by it being driven by, on average, two preganglionic neurons firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurons in healthy subjects (0.40 Hz). Likewise, the distribution of the number of spikes per cardiac interval was similar between the modeled and actual data: 0 spikes (69.5 vs 66.6%), 1 spike (25.6 vs 21.2%), 2 spikes (4.3 vs 6.4%), 3 spikes (0.5 vs 1.7%), and 4 spikes (0.1 vs 0.7%). Although some features of the firing patterns could be explained by the postganglionic neuron being driven by a single preganglionic neuron, none of the emulated firing patterns generated by the firing of three preganglionic neurons matched the discharge of the real neurons. These modeling data indicate that, on average, human postganglionic sympathetic neurons are driven by two preganglionic inputs.

The Riley–Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10–30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains their loss of deep tendon reflexes. Moreover, we suggest that their ataxic gait is sensory in origin, due to the loss of functional muscle spindles and hence a compromised sensorimotor control of locomotion.

The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

Arterial pulsations are known to modulate muscle spindle firing; however, the physiological significance of such synchronised modulation has not been investigated. Unitary recordings were made from 75 human muscle spindle afferents innervating the pretibial muscles. The modulation of muscle spindle discharge by arterial pulsations was evaluated by R-wave triggered averaging and power spectral analysis. We describe various effects arterial pulsations may have on muscle spindle afferent discharge. Afferents could be “driven” by arterial pulsations, e.g., showing no other spontaneous activity than spikes generated with cardiac rhythmicity. Among afferents showing ongoing discharge that was not primarily related to cardiac rhythmicity we illustrate several mechanisms by which individual spikes may become phase-locked. However, in the majority of afferents the discharge rate was modulated by the pulse wave without spikes being phase locked. Then we assessed whether these influences changed in two physiological conditions in which a sustained increase in muscle sympathetic nerve activity was observed without activation of fusimotor neurones: a maximal inspiratory breath-hold, which causes a fall in systolic pressure, and acute muscle pain, which causes an increase in systolic pressure. The majority of primary muscle spindle afferents displayed pulse-wave modulation, but neither apnoea nor pain had any significant effect on the strength of this modulation, suggesting that the physiological noise injected by the arterial pulsations is robust and relatively insensitive to fluctuations in blood pressure. Within the afferent population there was a similar number of muscle spindles that were inhibited and that were excited by the arterial pulse wave, indicating that after signal integration at the population level, arterial pulsations of opposite polarity would cancel each other out. We speculate that with close-to-threshold stimuli the arterial pulsations may serve as an endogenous noise source that may synchronise the sporadic discharge within the afferent population and thus facilitate the detection of weak stimuli.