Differential effects of radiant and mechanically applied thermal stimuli on human C-tactile afferent firing patterns.

C-tactile (CT) afferents respond to gentle tactile stimulation, but only a handful of studies in humans and animals have investigated whether their firing is modified by temperature. We describe the effects of radiant thermal stimuli, and of stationary and very slowly moving mechanothermal stimuli, on CT afferent responses. We find that CT afferents are primarily mechanoreceptors, as they fired little during radiant thermal stimuli, but they exhibited different patterns of firing during combined mechano-cool stimulation compared with warming. CTs fired optimally to gentle, very slowly moving, or stationary mechanothermal stimuli delivered at neutral temperature (~32°C, normal skin temperature), but they responded with fewer spikes (median 67% decrease) and at significantly lower rates (47% decrease) during warm (~42°C) tactile stimuli. During cool tactile stimuli (~18°C), their mean instantaneous firing frequency significantly decreased by 35%, but they often fired a barrage of afterdischarge spikes at a low frequency (~5 Hz) that outlasted the mechanical stimulus. These effects were observed under a variety of stimulus conditions, including during stationary and slowly moving touch (0.1 cm/s), and we complemented these tactile approaches using a combined electrical-thermal stimulation experiment where we found a suppression of spiking during warming. Overall, CT afferents are exquisitely sensitive to tactile events, and we show that their firing is modulated with touch temperatures above and below neutral skin temperature. Warm touch consistently decreased their propensity to fire, whereas cool touch produced lower firing rates but afterdischarge spiking. NEW & NOTEWORTHY C-tactile (CT) afferents are thought to underpin pleasant touch, and previous work has shown that they respond optimally to a slow caress delivered at typical (neutral) skin temperature. Here, we show that, although CTs are primarily mechanoreceptive afferents, they are modified by temperature: warm touch decreases their firing, whereas cool touch produces lower firing rates but long-lasting spiking, frequently seen as afterdischarges. This has implications for the encoding of affective sensory events in human skin.

Microneurography: how it started and how it works.

In the first section, this historical review describes endeavors to develop the method for recording normal nerve impulse traffic in humans, designated microneurography. The method was developed at the Department of Clinical Neurophysiology of the Academic Hospital in Uppsala, Sweden. Microneurography involves the impalement of a peripheral nerve with a tungsten needle electrode. Electrode position is adjusted by hand until the activity of interest is discriminated. Nothing similar had previously been tried in animal preparations, and thus the large number of preceding studies that recorded afferent activity in other mammals did not offer pertinent methodological guidance. For 2 years, the two scientists involved in the research impaled their own nerves with electrodes to test various kinds of needles and explore different neural systems, all the while carefully watching for signs of nerve damage. Temporary paresthesiae were common, whereas enduring sequelae never followed. Single-unit impulse trains could be discriminated, even those originating from unmyelinated fibers. An explanation for the discrimination of unitary impulses using a coarse electrode is inferred based on the electrical characteristics of the electrode placed in the flesh and the impulse shapes, as discussed in the second section of this paper. Microneurography and the microstimulation of single afferents, combined with psychophysical methods and behavioral tests, have generated new knowledge particularly regarding four neural systems, namely the proprioceptive system, the cutaneous mechanoreceptive system, the cutaneous nociceptive system, and the sympathetic efferent system to skin structures and muscular blood vessels. Examples of achievements based on microneurography are presented in the final section.

The neurophysiology of unmyelinated tactile afferents.

CT (C tactile) afferents are a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and other mammals. Evidence from patients lacking myelinated tactile afferents indicates that signaling in these fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch. CT fiber activation may also have a role in pain inhibition. This review outlines the growing evidence for unique properties and pathways of CT afferents.

Somatotopic organization of gentle touch processing in the posterior insular cortex.

A network of thin (C and A delta) afferents relays various signals related to the physiological condition of the body, including sensations of gentle touch, pain, and temperature changes. Such afferents project to the insular cortex, where a somatotopic organization of responses to noxious and cooling stimuli was recently observed. To explore the possibility of a corresponding body-map topography in relation to gentle touch mediated through C tactile (CT) fibers, we applied soft brush stimuli to the right forearm and thigh of a patient (GL) lacking A beta afferents, and six healthy subjects during functional magnetic resonance imaging (fMRI). For improved fMRI analysis, we used a highly sensitive multivariate voxel clustering approach. A somatotopic organization of the left (contralateral) posterior insular cortex was consistently demonstrated in all subjects, including GL, with forearm projecting anterior to thigh stimulation. Also, despite denying any sense of touch in daily life, GL correctly localized 97% of the stimuli to the forearm or thigh in a forced-choice paradigm. The consistency in activation patterns across GL and the healthy subjects suggests that the identified organization reflects the central projection of CT fibers. Moreover, substantial similarities of the presently observed insular activation with that described for noxious and cooling stimuli solidify the hypothesized sensory-affective role of the CT system in the maintenance of physical well-being as part of a thin-afferent homeostatic network.

Unmyelinated tactile afferents have opposite effects on insular and somatosensory cortical processing.

A previous functional magnetic resonance imaging (fMRI) study of an A-beta deafferented subject (GL) showed that stimulation of tactile C afferents (CT) activates insular cortex whereas no activation was seen in somatosensory cortices. Psychophysical studies suggested that CT afferents contribute to affective but not to discriminative aspects of tactile stimulation. We have now examined cortical processing following CT stimulation in a second similarly deafferented subject (IW), as well as revisited the data from GL. The results in IW showed similar activation of posterior insular cortex following CT stimulation as in GL and so strengthen the view that CT afferents underpin emotional aspects of touch. In addition, CT stimulation evoked significant fMRI deactivation in somatosensory cortex in both subjects supporting the notion that CT is not a system for discriminative touch.

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.

Discriminative touch and emotional touch.

Somatic sensation comprises four main modalities, each relaying tactile, thermal, painful, or pruritic (itch) information to the central nervous system. These input channels can be further classified as subserving a sensory function of spatial and temporal localization, discrimination, and provision of essential information for controlling and guiding exploratory tactile behaviours, and an affective function that is widely recognized as providing the afferent neural input driving the subjective experience of pain, but not so widely recognized as also providing the subjective experience of affiliative or emotional somatic pleasure of touch. The discriminative properties of tactile sensation are mediated by a class of fast-conducting myelinated peripheral nerve fibres--A-beta fibres--whereas the rewarding, emotional properties of touch are hypothesized to be mediated by a class of unmyelinated peripheral nerve fibres--CT afferents (C tactile)--that have biophysical, electrophysiological, neurobiological, and anatomical properties that drive the temporally delayed emotional somatic system. CT afferents have not been found in the glabrous skin of the hand in spite of numerous electrophysiological explorations of this area. Hence, it seems reasonable to conclude that they are lacking in the glabrous skin. A full understanding of the behavioural and affective consequences of the differential innervation of CT afferents awaits a fuller understanding of their function.

Unmyelinated tactile afferents underpin detection of low-force monofilaments.

Human hairy but not glabrous skin has unmyelinated (C) tactile (CT) afferents that project to insular cortex. We studied two subjects with the rare sensory neuronopathy syndrome who lack A-beta fibers but have relatively preserved C-fiber function. Weak monofilaments were detected on hairy skin alone. Hence, the ability to detect light touch does not depend entirely on the A-beta somatosensory system; CT afferents may contribute to the detection of weak monofilaments.

Microneurography: how the technique developed and its role in the investigation of the sympathetic nervous system.

A historical review is given of the development of microneurography and its application for studies of sympathetic nerve activity in humans.

Receptive field properties of unmyelinated tactile afferents in the human skin.

We recorded, with the microneurography technique, single-unit impulses from nine cutaneous mechanoreceptive afferents with conduction velocities in the C range and receptive fields in the hairy skin of the forearm. The units responded with high impulse rates to light touch and had low monofilament thresholds. The geography of receptive fields was explored with a scanning method: a lightweight probe with a small and rounded tip was made to scan the field area in a series of closely adjacent tracks while single-unit activity was recorded. The fields of the nine units varied considerably in size as well as complexity. The individual field consisted of one to nine small responsive spots distributed over an area of 1-35 mm(2) when explored with a moving indentation of 5 mN. The fields were roughly round or oval in shape with no preferred orientation. The size of the response differed between individual sensitive spots in a field, suggesting a highly nonuniform terminal organization. The properties of the fields seem consistent with a role of tactile C afferents to provide information about pleasant touch and skin-to-skin contacts to central structures controlling emotions and affiliative behavior.