A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine

Unmyelinated tactile (CT) afferents are abundant in arm hairy skin and have been suggested to signal features of social affective touch. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial (n=27), radial (n=8) and peroneal nerves (n=4). Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.

Low mechano-afferent fibers reduce thermal pain but not pain intensity in CRPS

Background Human hairy (not glabrous skin) is equipped with a subgroup of C-fibers, the C-tactile (CT) fibers. Those do not mediate pain but affective aspects of touch. CT-fiber-activation reduces experimental pain if they are intact. In this pilot study we investigated pain modulating capacities of CT-afferents in CRPS. Methods 10 CRPS-patients (mean age 33 years, SEM 3.3) and 11 healthy controls (mean age 43.2 years, SEM 3.9) participated. CT-targeted-touch (brush stroking, velocity: 3 cm/s) was applied on hairy and glabrous skin on the affected and contralateral limb. Patients rated pleasantness of CT-targeted-touch (anchors: 1 “not pleasant”—4 “very pleasant”) twice daily on 10 days. Pain intensity (NRS: 0 “no pain” – 10 “worst pain imaginable”) was assessed before, 0, 30, 60 and 120 min after each CT-stimulation. To assess sensory changes, quantitative-sensory-testing was performed at the beginning and the end of the trial period. Results CT-targeted-touch was felt more pleasant on the healthy compared to the affected limb on hairy (p < 0.001) and glabrous skin (p 0.002), independent of allodynia. In contrast to healthy controls patients felt no difference between stimulating glabrous and hairy skin on the affected limb. Thermal pain thresholds increased after CT-stimulation on the affected limb (cold-pain-threshold: p 0.016; heat-pain-threshold: p 0.033). Conclusions CT-stimulation normalizes thermal pain thresholds but has no effect on the overall pain in CRPS. Therefore, pain modulating properties of CT-fibers might be too weak to alter chronic pain in CRPS. Moreover, CT-fibers appear to lose their ability to mediate pleasant aspects of touch in CRPS.

A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine.

Numerous microneurography studies in the human peroneal nerve have suggested that CT afferents are lacking in the more distal parts of the limbs. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial, radial and peroneal nerves. Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, including a lack of responsiveness to heat, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.

Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder

An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (~3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.

Evidence for sparse C-tactile afferent innervation of glabrous human hand skin

C-tactile (CT) afferents were long-believed to be lacking in humans, but were subsequently shown to densely innervate the face and arm skin, and to a lesser extent the leg. Their firing frequency to stroking touch at different velocities has been correlated with ratings of tactile pleasantness. CT afferents were thought to be absent in human glabrous skin; however, tactile pleasantness can be perceived across the whole body, including glabrous hand skin. We used microneurography to investigate mechanoreceptive afferents in the glabrous skin of the human hand, during median and radial nerve recordings. We describe CTs found in the glabrous skin, with comparable characteristics to those in hairy arm skin, and detail recordings from three such afferents. CTs were infrequently encountered in the glabrous skin and we estimate that the ratio of recorded CTs relative to myelinated mechanoreceptors (1:80) corresponds to an absolute innervation density of around 7 times lower than in hairy skin. This sparse innervation sheds light on discrepancies between psychophysical findings of touch perception on glabrous skin and hairy skin, although the role of these CT afferents in the glabrous skin remains subject to future work.

Pleasantness Only?

When gently stroked with velocities between 0.1 and 30 cm/s, participants typically rate velocities around 3 cm/s as most pleasant, and the ratings follow an inverted u-shape. This pleasantness curve correlates often, but not always, with the firing rate of unmyelinated C-tactile (CT) afferents, leading to the notion that CT afferents code for the hedonic or emotional aspect of gentle touch. However, there is also evidence that CT firing does not necessarily equal pleasantness, and the range of attributes that CT afferents code for is not known. Here, participants were stroked with different velocities assumed to activate CT afferents to a different extent while they rated the touch on several sensory and emotional attributes. We expected an inverted u-shaped rating curve for pleasantness and other emotional attributes, but not for sensory attributes. Inverted u-shaped rating patterns were found for the emotional attributes “pleasant” and “not burdensome,” but also for the sensory attribute “rough.” CT-directed stimulation is thus not only experienced as hedonic. The sensations arising from CTs together with all other types of mechanoreceptors might be centrally integrated into a percept that represents those aspects which are most salient for the stimulation at hand.

The anticipation and perception of affective touch in women with and recovered from Anorexia Nervosa

Disruptions in reward processing and anhedonia have long being considered as possible contributors to the aetiology and maintenance of Anorexia nervosa (AN). Recently, interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialized, interoceptive C tactile system originating at the periphery, or a more top-down mechanism in the processing of pleasant tactile stimuli remains debated. Here, we investigated two related hypotheses. First, we examined whether the differences, between patients with AN and healthy controls in the perception of pleasantness of touch stimuli delivered in a CT-optimal manner versus a CT non-optimal manner would also be observed in patients recovered from AN. This is important as tactile anhedonia in acute patients may be the secondary result of prolonged malnutrition, rather than a deficit that contributed to the development of the disorder. Second, we examined whether these three groups would also differ in their top-down, anticipatory beliefs about the perceived pleasantness of different materials touching the skin, and to what degree such top-down beliefs and related impairments in alexithymia and interoceptive sensibility would explain any differences in perceived tactile plesantness. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic stroking touches applied to the forearm of 27 women with AN, 24 women who have recovered and 30 healthy controls using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than healthy controls, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in how CT optimal touch were perceived were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, this study concludes that tactile anhedonia in AN is not the secondary result of malnutrition but persists as a trait even after otherwise successful recovery of AN and also it not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of pleasant tactile experiences.

Affective Touch Dimensions: From Sensitivity to Metacognition

Touch can give rise to different sensations including sensory, emotional and social aspects. Tactile pleasure typically associated with caress-like skin stroking of slow velocities (1-10 cm/s) has been hypothesised to relate to an unmyelinated, slow-conducting C-tactile afferent system (CT system), developed to distinguish affective touch from the ‘‘noise’’ of other tactile information on hairy skin (the so-called ‘social touch hypothesis’). However, to date, there is no psychometric examination of the discriminative and metacognitive processes that contribute to accurate awareness of pleasant touch stimuli. Over two studies (total N= 194), we combined for the first time CT stimulation with signal detection theory and metacognitive measurements to assess the social touch hypothesis on the role of the CT system in affective touch discrimination. Participants’ ability to accurately discriminate pleasantness of tactile stimuli of different velocities, as well as their response bias, was assessed using a force-choice task (high versus low pleasantness response) on two different skin sites: forearm (CT-skin) and palm (non-CT skin). We also examined whether such detection accuracy was related to the confidence in their decision (metacognitive sensitivity). Consistently with the social touch hypothesis, we found higher sensitivity d’ on the forearm versus the palm, indicating that people are better at discriminating between stimuli of high and low tactile pleasantness on a skin site that contains CT afferents. Strikingly, we also found more negative response bias on the forearm versus the palm, indicating a tendency to experience all stimuli on CT-skin as ‘high-pleasant’, with such effects depending on order, likely to be explained by prior touch exposure. Finally, we found that people have greater confidence in their ability to discriminate between affective touch stimuli on CT innervated skin than on non-CT skin, possibly relating to the domain specificity of CT touch hence suggesting a domain-specific, metacognitive hypothesis that can be explored in future studies as an extension of the social touch hypothesis.HighlightsTouch mediated by C-tactile (CT) afferents on hairy skin elicits pleasant sensationsWe combine for the first time CT stimulation with signal detection theoryBetter accuracy to detect pleasantness of tactile stimuli at CT optimal speeds on CT skinHigher confidence in ability to accurately distinguish affective touch on CT skin

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.