Ingvars Birznieks

First spikes in ensembles of human tactile afferents code complex spatial fingertip events

It is generally assumed that primary sensory neurons transmit information by their firing rates. However, during natural object manipulations, tactile information from the fingertips is used faster than can be readily explained by rate codes. Here we show that the relative timing of the first impulses elicited in individual units of ensembles of afferents reliably conveys information about the direction of fingertip force and the shape of the surface contacting the fingertip. The sequence in which different afferents initially discharge in response to mechanical fingertip events provides information about these events faster than the fastest possible rate code and fast enough to account for the use of tactile signals in natural manipulation.

Effects of deep and superficial experimentally induced acute pain on muscle sympathetic nerve activity in human subjects

Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 ± 0.8 (s.e.m.) on a 0–10 visual analog scale (VAS) and lasting on average 358 ± 32 s, caused significant increases in MSNA (43.9 ± 10.0%), BP (5.4 ± 1.1%) and HR (7.0 ± 2.0%) – not the expected decreases. Skin pain, rated at 4.9 ± 0.6 and lasting 464 ± 54 s, also caused significant increases in MSNA (38.2 ± 12.8%), BP (5.1 ± 2.1%) and HR (5.6 ± 2.0%). The high‐frequency (HF) to low‐frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 ± 0.25 to 2.90 ± 0.45 for muscle pain and 2.80 ± 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well‐localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF : HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.

Slowly Adapting Mechanoreceptors in the Borders of the Human Fingernail Encode Fingertip Forces

There are clusters of slowly adapting (SA) mechanoreceptors in the skin folds bordering the nail. These “SA-IInail” afferents, which constitute nearly one fifth of the tactile afferents innervating the fingertip, possess the general discharge characteristics of slowly adapting type II (SA-II) tactile afferents located elsewhere in the glabrous skin of the human hand. Little is known about the signals in the SA-IInail afferents when the fingertips interact with objects. Here we show that SA-IInail afferents reliably respond to fingertip forces comparable to those arising in everyday manipulations. Using a flat stimulus surface, we applied forces to the finger pad while recording impulse activity in 17 SA-IInail afferents. Ramp-and-hold forces (amplitude 4 N, rate 10 N/s) were applied normal to the skin, and at 10, 20, or 30° from the normal in eight radial directions with reference to the primary site of contact (25 force directions in total). All afferents responded to the force stimuli, and the responsiveness of all but one afferents was broadly tuned to a preferred direction of force. The preferred directions among afferents were distributed all around the angular space, suggesting that the population of SA-IInail afferents could encode force direction. We conclude that signals in the population of SA-IInail afferents terminating in the nail walls contain vectorial information about fingertip forces. The particular tactile features of contacted surfaces would less influence force-related signals in SA-IInail afferents than force-related signals present in afferents terminating in the volar skin areas that directly contact objects.

Individual differences in the cardiovascular responses to tonic muscle pain: parallel increases or decreases in muscle sympathetic nerve activity, blood pressure and heart rate

We recently showed that acute muscle pain, induced by bolus intramuscular injection of hypertonic saline, causes a sustained increase in muscle sympathetic nerve activity (MSNA) and a modest increase in blood pressure and heart rate. However, it is not known whether long‐lasting (tonic) pain, which more closely resembles chronic pain, causes a sustained increase in MSNA and blood pressure. We tested this hypothesis by recording MSNA in 12 healthy subjects. Tonic pain was induced for ∼60 min by slow intramuscular infusion of hypertonic saline (7%) into the ipsilateral tibialis anterior muscle. Pain was sustained at a tolerable level (5/10 to 6/10 on a visual analog scale). Seven subjects showed progressive increases in mean MSNA amplitude during tonic pain, increasing to 154 ± 17% (SEM) at 45 min and remaining essentially constant for the duration of the infusion. In these subjects, blood pressure and heart rate also increased. Conversely, for the other five subjects MSNA showed a progressive decline, with a peak fall of 67 ± 11% at 40 min; blood pressure and heart rate also fell in these subjects. We conclude that tonic muscle pain has long‐lasting effects on the sympathetic control of blood pressure, causing a sustained increase in some subjects yet a sustained decrease in others. This may have implications for individual differences in the cardiovascular consequences of chronic pain.

Encoding of tangential torque in responses of tactile afferent fibres innervating the fingerpad of the monkey

Torsional loads are ubiquitous during everyday dextrous manipulations. We examined how information about torque is provided to the sensorimotor control system by populations of tactile afferents. Torsional loads of different magnitudes were applied in clockwise and anticlockwise directions to a standard central site on the fingertip. Three different background levels of contact (grip) force were used. The median nerve was exposed in anaesthetized monkeys and single unit responses recorded from 66 slowly adapting type‐I (SA‐I) and 31 fast adapting type‐I (FA‐I) afferents innervating the distal segments of the fingertips. Most afferents were excited by torque but some were suppressed. Responses of the majority of both afferent types were scaled by torque magnitude applied in one or other direction, with the majority of FA‐I afferent responses and about half of SA‐I afferent responses scaled in both directions. Torque direction affected responses in both afferent types, but more so for the SA‐I afferents. Latencies of the first spike in FA‐I afferent responses depended on the parameters of the torque. We used a Parzen window classifier to assess the capacity of the SA‐I and FA‐I afferent populations to discriminate, concurrently and in real‐time, the three stimulus parameters, namely background normal force, torque magnitude and direction. Despite the potentially confounding interactions between stimulus parameters, both the SA‐I and the FA‐I populations could extract torque magnitude accurately. The FA‐I afferents signalled torque magnitude earlier than did the SA‐I afferents, but torque direction was extracted more rapidly and more accurately by the SA‐I afferent population.

The effects of experimental muscle and skin pain on the static stretch sensitivity of human muscle spindles in relaxed leg muscles

Animal studies have shown that noxious inputs onto γ‐motoneurons can cause an increase in the activity of muscle spindles, and it has been proposed that this causes a fusimotor‐driven increase in muscle stiffness that is believed to underlie many chronic pain syndromes. To test whether experimental pain also acts on the fusimotor system in humans, unitary recordings were made from 19 spindle afferents (12 Ia, 7 II) located in the ankle and toe extensors or peronei muscles of awake human subjects. Muscle pain was induced by bolus intramuscular injection of 0.5 ml 5% hypertonic saline into tibialis anterior (TA); skin pain was induced by 0.2 ml injection into the overlying skin. Changes in fusimotor drive to the muscle spindles were inferred from changes in the mean discharge frequency and discharge variability of spindle endings in relaxed muscle. During muscle pain no afferents increased their discharge activity: seven afferents (5 Ia, 2 II) showed a decrease and six (4 Ia, 2 II) afferents were not affected. During skin pain of 13 afferents discharge rate increased in one (Ia) and decreased in two (1 Ia, 1 II). On average, the overall discharge rate decreased during muscle pain by 6.1% (P < 0.05; Wilcoxon), but remained essentially the same during skin pain. There was no detectable correlation between subjective pain level and the small change in discharge rate of muscle spindles. Irrespective of the type of pain, discharge variability parameters were not influenced (P > 0.05; Wilcoxon). We conclude that, contrary to the ‘vicious cycle’ hypothesis, acute activation of muscle or skin nociceptors does not cause a reflex increase in fusimotor drive in humans. Rather, our results are more aligned with the pain adaptation model, based on clinical studies predicting pain‐induced reductions of agonist muscle activity.

Spontaneous fluctuations in the peripheral photoplethysmographic waveform: roles of arterial pressure and muscle sympathetic nerve activity.

Assessment of spontaneous slow waves in the peripheral blood volume using the photoplethysmogram (PPG) has shown potential clinical value, but the physiological correlates of these fluctuations have not been fully elucidated. This study addressed the contribution of arterial pressure and muscle sympathetic nerve activity (MSNA) in beat-to-beat PPG variability in resting humans under spontaneous breathing conditions. Peripheral PPG waveforms were measured from the fingertip, earlobe, and toe in young and healthy individuals (n = 13), together with the arterial pressure waveform, electrocardiogram, respiration, and direct measurement of MSNA by microneurography. Cross-spectral coherence analysis revealed that among the PPG waveforms, low-frequency fluctuations (0.04-0.15 Hz) in the ear PPG had the highest coherence with arterial pressure (0.71 ± 0.15) and MSNA (0.44 ± 0.18, with a peak of 0.71 ± 0.16 at 0.10 ± 0.03 Hz). The normalized midfrequency powers (0.08-0.15 Hz), with an emphasis on the 0.1-Hz region, were positively correlated between MSNA and the ear PPG (r = 0.77, P = 0.002). Finger and toe PPGs had lower coherence with arterial pressure (0.35 ± 0.10 and 0.30 ± 0.11, respectively) and MSNA (0.33 ± 0.10 and 0.26 ± 0.10, respectively) in the LF band but displayed higher coherence between themselves (0.54 ± 0.09) compared with the ear (P < 0.001), which may suggest the dominance of regional vasomotor activities and a common sympathetic influence in the glabrous skin. These findings highlight the differential mechanisms governing PPG waveform fluctuations across different body sites. Spontaneous PPG variability in the ear includes a major contribution from arterial pressure and MSNA, which may provide a rationale for its clinical utility.

DIFFERENTIAL SENSITIVITY TO SURFACE COMPLIANCE BY TACTILE AFFERENTS IN THE HUMAN FINGER PAD

We undertook a neurophysiological investigation of the responses of low-threshold mechanoreceptors in the human finger pad to surfaces of differing softness. Unitary recordings were made from 26 slowly adapting type I (SAI), 17 fast-adapting type I (FAI), and 9 slowly adapting type II (SAII) afferents via tungsten microelectrodes inserted into the median nerve at the wrist. A servo-controlled stimulator applied ramp-and-hold forces (1, 2, 4 N) at a constant loading and unloading rate (2 N/s) via a flat silicone disc over the center of the finger pad. Nine discs were used, which linearly increased in stiffness across the range. Population responses of the SAI afferents showed the greatest sensitivity to compliance, with a steep monotonic increase in mean firing rate with increasing stiffness (decreasing compliance) of the surface during the loading and plateau (but not unloading) phases. FAI afferents also showed a linear increase in firing during the loading but not unloading phase, although the slope was significantly lower than that of the SAI afferents at all amplitudes. Conversely, SAII afferents were influenced by object compliance only in certain conditions. Given their high density in the finger pads and their linear relationship between firing rate and object compliance during the loading and plateau phases, SAI afferents (together with FAI afferents during the loading phase) are ideally suited to contributing information on surface compliance to the overall estimation of softness, but the SAII afferents appear to play only a minor role.

Tonic muscle pain does not increase fusimotor drive to human leg muscles: implications for chronic muscle pain

•  What is the central question of this study? Based on data obtained from experimental animals, muscle pain is believed to cause a reflex activation of fusimotor neurones and thereby increase the sensitivity of muscle spindles to stretch. Using a model of long‐lasting muscle pain, we asked the question: does tonic muscle pain increase the resting discharge of muscle spindles in human subjects? •  What is the main finding and its importance? Microelectrode recordings from single muscle spindle afferents revealed no net change in the discharge of spontaneously active spindle endings during moderate–strong pain lasting ∼1 h. We conclude that, unlike the situation in anaesthetized animals, muscle pain does not cause a reflex increase in fusimotor drive and spindle discharge.

Muscle spindles in human tibialis anterior encode muscle fascicle length changes

Muscle spindles provide exquisitely sensitive proprioceptive information regarding joint position and movement. Through passively driven length changes in the muscle-tendon unit (MTU), muscle spindles detect joint rotations because of their in-parallel mechanical linkage to muscle fascicles. In human microneurography studies, muscle fascicles are assumed to follow the MTU and, as such, fascicle length is not measured in such studies. However, under certain mechanical conditions, compliant structures can act to decouple the fascicles, and, therefore, the spindles, from the MTU. Such decoupling may reduce the fidelity by which muscle spindles encode joint position and movement. The aim of the present study was to measure, for the first time, both the changes in firing of single muscle spindle afferents and changes in muscle fascicle length in vivo from the tibialis anterior muscle (TA) during passive rotations about the ankle. Unitary recordings were made from 15 muscle spindle afferents supplying TA via a microelectrode inserted into the common peroneal nerve. Ultrasonography was used to measure the length of an individual fascicle of TA. We saw a strong correlation between fascicle length and firing rate during passive ankle rotations of varying rates (0.1-0.5 Hz) and amplitudes (1-9°). In particular, we saw responses observed at relatively small changes in muscle length that highlight the sensitivity of the TA muscle to small length changes. This study is the first to measure spindle firing and fascicle dynamics in vivo and provides an experimental basis for further understanding the link between fascicle length, MTU length, and spindle firing patterns.NEW & NOTEWORTHY Muscle spindles are exquisitely sensitive to changes in muscle length, but recordings from human muscle spindle afferents are usually correlated with joint angle rather than muscle fascicle length. In this study, we monitored both muscle fascicle length and spindle firing from the human tibialis anterior muscle in vivo. Our findings are the first to measure these signals in vivo and provide an experimental basis for exploring this link further.