India Morrison

Coding of pleasant touch by unmyelinated afferents in humans

Pleasant touch sensations may begin with neural coding in the periphery by specific afferents. We found that during soft brush stroking, low-threshold unmyelinated mechanoreceptors (C-tactile), but not myelinated afferents, responded most vigorously at intermediate brushing velocities (1−10 cm s−1), which were perceived by subjects as being the most pleasant. Our results indicate that C-tactile afferents constitute a privileged peripheral pathway for pleasant tactile stimulation that is likely to signal affiliative social body contact.

Vicarious responses to pain in anterior cingulate cortex: is empathy a multisensory issue?

Results obtained with functional magnetic resonance imaging show that both feeling a moderately painful pinprick stimulus to the fingertips and witnessing another person’s hand undergo similar stimulation are associated with common activity in a pain-related area in the right dorsal anterior cingulate cortex (ACC). Common activity in response to noxious tactile and visual stimulation was restricted to the right inferior Brodmann’s area 24b. These results suggest a shared neural substrate for felt and seen pain for aversive ecological events happening to strangers and in the absence of overt symbolic cues. In contrast to ACC 24b, the primary somatosensory cortex showed significant activations in response to both noxious and innocuous tactile, but not visual, stimuli. The different response patterns in the two areas are consistent with the ACC’s role in coding the motivational-affective dimension of pain, which is associated with the preparation of behavioral responses to aversive events.

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.

The skin as a social organ

In general, social neuroscience research tends to focus on visual and auditory channels as routes for social information. However, because the skin is the site of events and processes crucial to the way we think about, feel about, and interact with one another, touch can mediate social perceptions in various ways. This review situates cutaneous perception within a social neuroscience framework by discussing evidence for considering touch (and to some extent pain) as a channel for social information. Social information conveys features of individuals or their interactions that have potential bearing on future interactions, and attendant mental and emotional states. Here, we discuss evidence for an affective dimension of touch and explore its wider implications for the exchange of social information. We consider three important roles for this affective dimension of the cutaneous senses in the transmission and processing of social information: first, through affiliative behavior and communication; second, via affective processing in skin–brain pathways; and third, as a basis for intersubjective representation.

Feeling good: on the role of C fiber mediated touch in interoception

The human skin is innervated by a network of thin, slow-conducting afferent (C and Aδ) fibers, transmitting a diverse range of information. Classically, these fibers are described as thermo-, noci- or chemoreceptive, whereas mechanoreception is attributed exclusively to thick, fast-conducting (Aβ) afferents. A growing body of evidence, however, supports the notion that C tactile afferents comprise a second anatomically and functionally distinct system signaling touch in humans. This review discusses established as well as recent findings which highlight fundamental differences in peripheral and central information coding and processing between Aβ and C mechanoreception. We conclude that from the skin through the brain, C touch shares more characteristics with interoceptive modalities (e.g. pain, temperature, and itch) than exteroceptive Aβ touch, vision or hearing. In this light, we discuss the motivational-affective role of C touch as an integral part of a thin-fiber afferent homeostatic network for the maintenance of physical and social well-being.

Altered C-tactile processing in human dynamic tactile allodynia

Summary Psychophysical and fMRI findings suggest reduced C‐tactile mediated hedonic processing in tactile allodynia. However, Aβ signaling is required for the perception of allodynic pain. ABSTRACT Human unmyelinated (C) tactile afferents signal the pleasantness of gentle skin stroking on hairy (nonglabrous) skin. After neuronal injury, that same type of touch can elicit unpleasant sensations: tactile allodynia. The prevailing pathophysiological explanation is a spinal cord sensitization, triggered by nerve injury, which enables Aβ afferents to access pain pathways. However, a recent mouse knockout study demonstrates that C‐tactile afferents are necessary for allodynia to develop, suggesting a role for not only Aβ but also C‐tactile afferent signaling. To examine the contribution of C‐tactile afferents to the allodynic condition in humans, we applied the heat/capsaicin model of tactile allodynia in 43 healthy subjects and in 2 sensory neuronopathy patients lacking Aβ afferents. Healthy subjects reported tactile‐evoked pain, whereas the patients did not. Instead, patients reported their C‐touch percept (faint sensation of pleasant touch) to be significantly weaker in the allodynic zone compared to untreated skin. Functional magnetic resonance imaging in 18 healthy subjects and in 1 scanned patient indicated that stroking in the allodynic and control zones evoked different responses in the primary cortical receiving area for thin fiber signaling, the posterior insular cortex. In addition, reduced activation in the medial prefrontal cortices, key areas for C‐tactile hedonic processing, was identified. These findings suggest that dynamic tactile allodynia is associated with reduced C‐tactile mediated hedonic touch processing. Nevertheless, because the patients did not develop allodynic pain, this seems dependent on Aβ signaling, at least under these experimental conditions.

Where Pain Meets Action in the Human Brain

Pains complex influence on behavior implies that it involves an action component, although little is known about how the human brain adaptively translates painful sensations into actions. The consistent activation of premotor and motor-related regions during pain, including the midcingulate cortex (MCC), raises the question of whether these areas contribute to an action component. In this fMRI experiment, we controlled for voluntary action-related processing during pain by introducing a motor task during painful or nonpainful stimulation. The MCC (particularly the caudal cingulate motor zone [CCZ]), motor cortex, thalamus, and cerebellum responded during action regardless of pain. Crucially, however, these regions did not respond to pain unless an action was performed. Reaction times were fastest during painful stimulation and correlated with CCZ activation. These findings are consistent with the results of an activation likelihood estimate meta-analysis in which activation across experiments involving pain, action execution, or action preparation (with a total of 4929 subjects) converged in a similar network. These findings suggest that specific motor-related areas, including the CCZ, play a vital role in the control and execution of context-sensitive behavioral responses to pain. In contrast, bilateral insular cortex responded to pain stimulation regardless of action.

Pleasant touch moderates the subjective but not objective aspects of body perception

Un-myelinated C tactile afferents (CT afferents) are a key finding in affective touch. These fibers, which activate in response to a caress-like touch to hairy skin (CT afferents are not found in palm skin), may have more in common with interoceptive systems encoding body ownership, than afferent systems processing other tactile stimuli. We tested whether subjective embodiment of a rubber hand (measured through questionnaire items) was increased when tactile stimulation was applied to the back of the hand at a rate optimal for CT afferents (3 cm/s) vs. stimulation of glabrous skin (on the palm of the hand) or at a non-optimal rate (30 cm/s), which should not activate these fibers. We also collected ratings of tactile pleasantness and a measure of perceived limb position, proprioceptive drift, which is mediated by different mechanisms of multisensory integration than those responsible for feelings of ownership. The results of a multiple regression analysis revealed that proprioceptive drift was a significant predictor of subjective strength of the illusion when tactile stimuli were applied to the back of the hand, regardless of stroking speed. This relationship was modified by pleasantness, with higher ratings when stimulation was applied to the back of the hand at the slower vs. faster stroking speed. Pleasantness was also a unique predictor of illusion strength when fast stroking was applied to the palm of the hand. However, there were no conditions under which pleasantness was a significant predictor of drift. Since the illusion was demonstrated at a non-optimal stroking speed an integrative role for CT afferents within the illusion cannot be fully supported. Pleasant touch, however, does moderate the subjective aspects of the rubber hand illusion, which under certain tactile conditions may interact with proprioceptive information about the body or have a unique influence on subjective body perception.

Seeking pleasant touch: neural correlates of behavioral preferences for skin stroking

Affective touch is a dynamic process. In this fMRI study we investigated affective touch by exploring its effects on overt behavior. Arm and palm skin were stroked with a soft brush at five different velocities (0.3, 1, 10, 3, and 30 cm s−1), using a novel feedback-based paradigm. Following stimulation in each trial, participants actively chose whether the caress they would receive in the next trial would be the same speed (“repeat”) or different (“change”). Since preferred stroking speeds should be sought with greater frequency than non-preferred speeds, this paradigm provided a measure of such preferences in the form of active choices. The stimulation velocities were implemented with respect to the differential subjective pleasantness ratings they elicit in healthy subjects, with intermediate velocities (1, 10, and 3 cm s−1) considered more pleasant than very slow or very fast ones. Such pleasantness ratings linearly correlate with changes in mean firing rates of unmyelinated low-threshold C-tactile (CT) afferent nerves in the skin. Here, gentle, dynamic stimulation optimal for activating CT-afferents not only affected behavioral choices, but engaged brain regions involved in reward-related behavior and decision-making. This was the case for both hairy skin of the arm, where CTs are abundant, and glabrous skin of the palm, where CTs are absent. These findings provide insights on central and behavioral mechanisms underlying the perception of affective touch, and indicate that seeking affective touch involves value-based neural processing that is ultimately reflected in behavioral preferences.

Facets and mechanisms of adaptive pain behavior: predictive regulation and action

Neural mechanisms underlying nociception and pain perception are considered to serve the ultimate goal of limiting tissue damage. However, since pain usually occurs in complex environments and situations that call for elaborate control over behavior, simple avoidance is insufficient to explain a range of mammalian pain responses, especially in the presence of competing goals. In this integrative review we propose a Predictive Regulation and Action (PRA) model of acute pain processing. It emphasizes evidence that the nervous system is organized to anticipate potential pain and to adjust behavior before the risk of tissue damage becomes critical. Regulatory processes occur on many levels, and can be dynamically influenced by local interactions or by modulation from other brain areas in the network. The PRA model centers on neural substrates supporting the predictive nature of pain processing, as well as on finely-calibrated yet versatile regulatory processes that ultimately affect behavior. We outline several operational categories of pain behavior, from spinally-mediated reflexes to adaptive voluntary action, situated at various neural levels. An implication is that neural processes that track potential tissue damage in terms of behavioral consequences are an integral part of pain perception.