Sensory Systems · Unit 2: Touch

Hairy Skin, Stroking and Affective Touch

What detects a slow stroke across hairy skin, and what is known about why it can feel good? This lesson reads the human C-tactile evidence (microneurography, pleasantness ratings, a deafferented patient, cordotomy patients), sets it beside mouse work on C-LTMRs, MrgprB4 neurons and Aβ field-LTMRs, and follows the mouse experiments that tie gentle touch to place preference, sexual receptivity, accumbens dopamine and oxytocin neurons. You will be able to read a velocity-tuning fit, keep mouse and human outcomes apart, and design a test of whether an adult afferent class is needed for rewarding touch.

Watch first A Match Between Two Curves · 2:51

Stroke the hairy skin of a human forearm with a soft brush at a few centimetres per second, and one class of slow, unmyelinated nerve fibre fires harder than it does for slower or faster strokes. Ask people to rate the same strokes, and they call those middle speeds the most pleasant.

The core lesson on touch and pain noted that some C fibres are low-threshold touch afferents rather than nociceptors, and the low-threshold mechanoreceptors placed C-LTMRs and Aδ endings on mouse hair follicles. This lesson asks two narrower questions. What detects a slow stroke? And what is known, and not known, about why it can feel good? The short answers: more than one afferent class, and much less than popular accounts suggest.

The idea: a slow brush is tuned like a stimulus feature

A C-tactile (CT) afferent is a human low-threshold mechanoreceptor with an unmyelinated axon. It is the human counterpart of what mouse papers call a C-LTMR (C-fibre low-threshold mechanoreceptor), although whether the two terms name the same cells is a question this lesson ends on. Unmyelinated touch afferents had been recorded in human hairy skin before 2009 (Johansson 1988, Nordin 1990, Vallbo 1999), but what they were for was still a hypothesis.

Löken, Wessberg, Morrison, McGlone and Olausson (Nature Neuroscience, 2009) treated stroke velocity as a stimulus feature, the way sensory coding treats orientation or frequency. Microneurography is a fine electrode passed through the skin into a peripheral nerve to record single axons in an awake person. They recorded single CT afferents from the forearm of healthy volunteers while a soft brush crossed the receptive field at a range of controlled velocities. CT firing traced an inverted U, highest for strokes between about 1 and 10 cm/s.

In separate sessions, a separate group of volunteers rated how pleasant the same strokes felt. Their ratings traced the same inverted U. Think of two thermometers in different rooms that both read highest at noon: they agree, but neither shows that one causes the other. The 2009 result is a correspondence between two tuning curves measured in different people. It does not show that CT firing is needed for pleasantness, or that it is the only input to it.

Stroking is not one receptor: field-LTMRs and C fibres in mouse

In mouse hairy skin, at least three afferent populations are candidates for detecting a stroke, and they are not the same cells.

TH-positive C-LTMRs. Li and colleagues in the Ginty laboratory (Cell, 2011) used an ex vivo preparation of skin, nerve, dorsal root ganglion and spinal cord from mice aged 2 to 3 months, recorded from sensory neurons and then identified them. Neurons marked by tyrosine hydroxylase (TH) were C-LTMRs, with a mean conduction velocity of 0.58 ± 0.02 m/s in that preparation. Their endings were lanceolate: nerve terminals that run lengthwise along a hair follicle, parallel to the hair shaft. They sat on zigzag and awl/auchene follicles (two of the mouse hair types). The TH-positive population did not express MrgprB4. LTMRs innervating the same or neighbouring follicles sent central projections into narrow dorsal horn columns, which the authors read as support for local integration, the topic of the dorsal horn lesson.

MrgprB4 neurons. Liu and colleagues in David Anderson’s laboratory (Nature Neuroscience, 2007) used a genetic tracer to follow sensory neurons expressing the receptor MrgprB4. The fibres were unmyelinated and nonpeptidergic and innervated hairy skin only. That paper was anatomy. Its link to tactile C fibres was a suggestion, not a recording.

Aβ field-LTMRs. Bai, Lehnert and colleagues in the Ginty laboratory (Cell, 2015) used intersectional TrkC and Ret genetics to reach a class whose endings are circumferential: they wrap around the follicle instead of running along it. A field-LTMR is a large myelinated afferent of this type with a broad receptive field. In vivo recordings from the ganglia showed that these neurons did not respond to deflection of a single hair and needed indentation forces in the noxious range, yet they fired to gentle stroking of the skin. One neuron could form as many as 180 circumferential endings. The authors proposed that the neuron sums many weakly sensitive endings, so a stroke that moves many follicles at once reaches threshold when no single hair can. A single hair is a lever; a field-LTMR is a net. The paper did not test pleasantness or reward.

So gentle stroking is not a C-fibre job alone. Any claim that “the stroking receptor” drives a behaviour has to say which of these classes it manipulated.

AI-generated illustration: two skin blocks side by side. On the left a thin unsheathed C-LTMR axon ends in gold terminals running lengthwise along a hair follicle; on the right a thick myelinated Aβ field-LTMR axon ends in gold rings wrapped around a follicle. An inset shows one axon branching to a ring ending on each of five follicles while a broad arrow strokes across the hairs.
TH-positive C-LTMR endings run lengthwise along the follicle, while Aβ field-LTMR endings wrap around it. One field-LTMR can form as many as 180 such endings, and Bai and colleagues proposed that it sums them, so a stroke across many follicles reaches threshold when no single hair can.

From skin to reward in mice

Four groups have manipulated mouse touch afferents or their central targets and measured behaviour. Keep each outcome as measured.

Vrontou and colleagues (Nature, 2013) imaged calcium in the spinal terminals of MrgprB4-positive neurons in anaesthetized mice at least 8 weeks old. The terminals responded to massage-like stroking of hairy skin delivered at about 0.5 to 2 cm/s. That is the protocol’s speed, not an estimate of the mouse optimum, and the human 1 to 10 cm/s band should not be carried across. In a separate experiment with male mice about one month old, a DREADD (a designer receptor activated only by a synthetic ligand) was used to activate MrgprB4 neurons, and the mice developed a conditioned place preference: they spent more time in the chamber paired with activation. The authors read this as positive reinforcement, anxiolysis or both.

AI-generated illustration: three panels of a two-chamber box seen from above. A mouse is first placed in one chamber while its MrgprB4 neurons are activated, then in the other chamber without activation, then left free and found in the chamber paired with activation.
In Vrontou and colleagues' DREADD experiment, male mice about one month old came to spend more time in the chamber paired with MrgprB4 activation. The authors read this as positive reinforcement, anxiolysis or both, not as a report of pleasure.

Elias and colleagues in the Abdus-Saboor laboratory (Cell, 2023) worked with adult female mice and a Cre line that marks the developmental Mrgprb4 lineage, that is, every cell that expressed Mrgprb4 at some point, not only those expressing it in adulthood. Optogenetic activation of these afferents in back skin produced place preference and a dorsiflexion resembling lordosis, the arched posture a receptive female mouse takes during mating. Ablating the lineage reduced sexual receptivity. Stimulating the lineage evoked dopamine release in the brain, and in ablated females a dopamine-sensor signal in the nucleus accumbens, measured by fibre photometry, was reduced during mounting. A dopamine signal is a neuromodulator readout tied to reward prediction and motivation (motivation and reward), not a measure of pleasure.

Yu and colleagues (Neuron, 2022) started from the brain. Touch-like tactile stimulation increased the firing of oxytocin neurons in the paraventricular nucleus of the hypothalamus (PVH), and Tac1-positive neurons in the lateral and ventrolateral periaqueductal gray sent monosynaptic excitatory projections onto them. Reducing Tac1-neuron activity abolished the touch-evoked oxytocin firing. The stimulus promoted social interaction and place preference. The study did not test which peripheral afferents are needed; it is not evidence about Mrgprb4 neurons. Oxytocin’s wider roles belong to the hypothalamus lesson.

Huzard and colleagues (Science Advances, 2022) deleted the calcium channel CaV3.2 in the Nav1.8 lineage of male mice, a developmental deletion that the authors took to impair C-LTMR function (Nav1.8 is not restricted to C-LTMRs), and the mice showed fewer social and tactile interactions. Transient chemogenetic enhancement of C-LTMR excitability in adults promoted touch seeking. The authors could not tell whether the DREADD activated the neurons directly or only potentiated them.

What human patients and lesions say

Three human studies test the 2009 picture from different angles.

A deafferented patient. Olausson and colleagues (Nature Neuroscience, 2002) studied a person lacking large myelinated afferents. CT stimulation of hairy skin produced a faint, pleasant sensation, and functional MRI showed insular activation with no detectable activity in primary or secondary somatosensory cortex. The authors proposed that CT input may underlie emotional and affiliative responses to caress-like touch. The insular link is one patient and one imaging method; emotion and stress discusses what an insular activation can and cannot mean.

Glabrous skin. Watkins and colleagues (Journal of Neurophysiology, 2021) recorded three CT afferents in human glabrous hand skin, about 1 for every 80 myelinated mechanoreceptors recorded, and estimated CT density there at around seven times lower than in hairy skin. Human CTs are sparse in the palm, not absent.

Cordotomy. An anterolateral cordotomy cuts the anterolateral spinal cord to relieve intractable pain. Marshall and colleagues (eLife, 2019) reported on 19 adults with refractory cancer pain tested before and after the operation (a twentieth recruit could not be tested afterwards). A brush crossed a marked 10 cm path on the dorsal forearm at 0.3, 3 and 30 cm/s, and patients rated pleasantness from -10 to +10. Pain, temperature and itch were markedly disrupted, but pleasantness ratings were not significantly changed. If CT pleasantness travelled only in the anterolateral tract, the cut should have removed it. The result rules out one obligatory route; it does not say which route carries the signal instead.

Worked problem: reading the fit. For the pain-affected side before cordotomy, the authors fitted the group’s ratings with a quadratic in log velocity:

y = -2.07x² + 1.88x + 6.22, where x = log10(v in cm/s), R² = 0.22

  1. Find the peak. dy/dx = -4.14x + 1.88. Set it to zero: x = 1.88 / 4.14 = 0.454. The second derivative is -4.14, so this is a maximum.
  2. Convert to velocity. v = 10^0.454 = 2.85 cm/s.
  3. Peak rating. x² = 0.206, so y = -2.07(0.206) + 1.88(0.454) + 6.22 = -0.427 + 0.854 + 6.22 = 6.65.
  4. Predicted ratings at the tested speeds. At 0.3 cm/s, x = -0.523 and y = -0.566 - 0.983 + 6.22 = 4.67. At 3 cm/s, x = 0.477 and y = -0.471 + 0.897 + 6.22 = 6.65. At 30 cm/s, x = 1.477 and y = -4.517 + 2.777 + 6.22 = 4.48.
  5. Interpret. The fitted peak, 2.85 cm/s, sits inside Löken’s 1 to 10 cm/s band, so the patients’ group curve has the familiar shape. But R² = 0.22 means velocity explains about a fifth of the variance in the ratings; the rest is left unexplained by the fit. And a fit to ratings cannot show that CT afferents are needed. The same study found that pleasantness survived the lesion.
Reading a velocity-tuning fit⚙ original · interactive
Jump to cm/s
x = log10(v)
0.000
Predicted rating y
6.22
Slope dy/dx (points per tenfold change)
1.88

R² = 0.22: velocity explains about a fifth of the variance in the ratings; most of it lies between people and trials.

In this sketch: one published group quadratic, drawn between the lowest and highest tested speeds (0.3 and 30 cm/s); only 0.3, 3 and 30 cm/s were tested, so the curve between them is the fit's interpolation, for the pain-affected side before cordotomy. No individual ratings and no CT firing curve are drawn.

A group quadratic from the Marshall 2019 cancer-pain patients tested before cordotomy; the correspondence with CT tuning is between curves measured in different people, and no mouse outcome is shown.

Which mouse neuron is a CT afferent, and what “pleasant” can mean in a mouse

The cross-species match is unsettled. TH-positive C-LTMRs and MrgprB4 neurons are different populations, and Huzard and colleagues described the identity of the mouse population best matching human CTs as controversial. A 2025 study by Du and colleagues (iScience) imaged the Mrgprb4 lineage in mice of both sexes aged 8 to 16 weeks and found responses to both mechanical and thermal stimuli; mice lacking the lineage lost a conditioned preference for mild pressure. A polymodal lineage is a poor fit for a pure “pleasant touch” line. The sensory neuron atlas lesson explains why a transcriptomic class is not yet a function. Settling the match would need human molecular data tied to physiologically identified units, for example markers measured in human ganglion neurons whose responses to slow stroking have been recorded, set against the mouse types.

The second gap is the word itself. In people, “pleasant” is a rating. In a mouse it can only be an outcome: time in a chamber, a posture, a dopamine-sensor signal, contact with cage mates. Each is useful; none is a report of feeling, and none licenses a claim about human health or wellbeing. The forward lessons on touch in autism models and itch return to these afferents from other angles, and circuit experiment design sets out the logic of necessity and sufficiency used below.

Design problem

Elias and colleagues used a developmental Mrgprb4 lineage. Design experiments to test whether Mrgprb4-expressing afferents in adult mice are needed for rewarding touch, and say what each result would and would not show.

One way to do it

Access in adults. Use an inducible driver for Mrgprb4, such as a CreER line if a validated one exists (otherwise it must be built and validated first), and give tamoxifen to adult mice, so that only cells expressing the marker then are targeted. Confirm recombination in the ganglia with a reporter and check which cells are labelled, since the lineage and the adult population may differ. Include tamoxifen-treated mice lacking the driver.

Two separate arms. Sufficiency: activate the adult population (optogenetically or chemogenetically) and measure place preference. Necessity: ablate or silence it in adults (diphtheria toxin receptor, or an inhibitory DREADD), then measure receptivity to a male and the accumbens dopamine-sensor signal during mounting by fibre photometry. Activation alone cannot show need.

Controls for other explanations. Measure locomotion and posture so a motor change is not read as receptivity, and run an anxiety assay so anxiolysis is not read as reward. Test both sexes if the claim is general.

Check the modality. Image the targeted neurons to stroking, pressure and temperature (Du and colleagues found polymodality in the lineage). If they respond to more than touch, call the result “required for this behaviour,” not “a pleasure line.”

Human counterpart. A mouse marker cannot stand in for a human CT afferent. A human claim needs microneurography with pleasantness ratings in the same people and, eventually, molecular identification of the recorded fibre class.

How we measure it

Microneurography with psychophysics

A fine electrode inserted through the skin into a peripheral nerve records single afferent axons in an awake person while a controlled stimulus is applied. Paired with ratings, it lets you compare a fibre's tuning with what people report, though in Löken 2009 the two came from separate groups.

Intersectional and lineage genetics (Cre, CreER, Flp)

Recombinase lines give access to a sensory neuron class for labelling, recording, ablation or activation. A constitutive Cre marks every cell that ever expressed the driver (a lineage); an inducible CreER given tamoxifen in adulthood marks cells expressing it then; combining two drivers narrows the class.

In vivo calcium imaging of afferent terminals

A genetically encoded calcium indicator in a defined afferent population is imaged at its spinal terminals in an anaesthetized mouse while the skin is stroked or poked. It shows which stimuli drive the population, at the level of the terminals imaged.

Fibre photometry with a dopamine sensor

An optical fibre over a brain region collects fluorescence from a genetically encoded dopamine sensor during behaviour. It reports changes in extracellular dopamine signal there, not a feeling.

Finish line

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Next · Lesson 8

Where Touch Is First Processed: Dorsal Horn and Dorsal Column Nuclei

A touch signal that reaches the brainstem has often been through the spinal cord's circuitry first. What does that circuitry do to it?

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Line S. Löken

Line S. Löken

First author of the 2009 Nature Neuroscience paper showing that human C-tactile afferents fire most to brush strokes at 1 to 10 cm/s, the same middle range that a separate group of participants rated most pleasant.

By the 2000s, microneurography had shown that human hairy skin contains unmyelinated afferents that respond to light touch, but what they were for was unclear. In the paper published in Nature Neuroscience in 2009, Line Löken, Johan Wessberg, India Morrison, Francis McGlone and Håkan Olausson asked a direct question: does the firing of these fibres follow how pleasant a stroke feels? They moved a soft brush across the forearm at a range of controlled velocities while recording single C-tactile afferents in awake volunteers. In separate sessions, with a separate group of participants, people rated how pleasant the same strokes felt. Both measures traced an inverted U, highest between about 1 and 10 cm/s. The paper did not test whether the fibres are needed for the feeling; it showed a correspondence. What it made possible was a quantitative handle on affective touch: a stimulus range, a fibre class and a rating that other laboratories could test in patients, in development and in animals.

✓ verbatim Löken, Wessberg, Morrison, McGlone & Olausson, Nature Neuroscience (2009), including its author-contributions statement.
Håkan Olausson

Håkan Olausson

First author of the 2002 study of a patient lacking large myelinated afferents who still felt faint, pleasant touch from CT stimulation, with insular but no detectable S1 or S2 activation, and was senior author of the 2009 velocity-tuning paper and an author on the 2019 cordotomy study.

A healthy person cannot feel CT input on its own, because any brush that excites CT afferents also excites large myelinated touch fibres. Olausson and colleagues found a way around that problem in a rare patient. In their 2002 Nature Neuroscience paper they studied a person who had lost large myelinated afferents, so that unmyelinated input from the skin was left largely alone. When the hairy skin was stroked in a way that excites CT afferents, the patient reported a faint, pleasant sensation. Functional MRI showed activation in the insular region and none detectable in primary or secondary somatosensory cortex. The authors proposed that CT input may underlie emotional and affiliative responses to caress-like touch, a hypothesis rather than a demonstration. The case turned CT afferents from a curiosity of nerve recordings into a candidate input for a separate, affective channel of touch, and it framed the cordotomy and velocity studies that followed.

✓ verbatim Olausson et al., Nature Neuroscience (2002); Löken et al., Nature Neuroscience (2009); Marshall et al., eLife (2019), article 51642.
David D. Ginty

David D. Ginty

Final author of Li et al. 2011 (Cell), which identified TH-positive mouse C-LTMRs and their lanceolate endings, and of Bai et al. 2015 (Cell), which described Aβ field-LTMRs that respond to stroking but not to the deflection of a single hair.

The mouse work on hairy skin depends on genetic access: a way to label one class of sensory neuron and then record from it. In the 2011 Cell paper by Li, Rutlin, Abraira and colleagues in the Ginty laboratory, neurons marked by tyrosine hydroxylase (TH) were identified in an ex vivo skin, nerve, ganglion and spinal cord preparation from adult mice as C-LTMRs, with lanceolate endings around particular hair follicles. In 2015 Ling Bai and Brendan Lehnert, sharing first authorship, used intersectional TrkC and Ret genetics to reach a different class whose endings wrap around follicles. In vivo recordings showed that these Aβ field-LTMRs ignored the deflection of a single hair yet responded to gentle stroking of the skin, and one neuron could form up to 180 such endings. These studies replaced the idea of one stroke detector with a set of afferent classes, each with its own anatomy, that can be compared in the same skin.

✓ verbatim Li et al., Cell (2011); Bai et al., Cell (2015).
Ishmail Abdus-Saboor

Ishmail Abdus-Saboor

Final author of Elias et al. 2023 (Cell), which linked a mouse Mrgprb4 lineage of sensory neurons to place preference, a lordosis-like posture, female sexual receptivity and nucleus accumbens dopamine signals.

Earlier work had shown that MrgprB4-expressing mouse neurons respond to stroking and that activating them can support place preference. Elias and colleagues, in the laboratory of Ishmail Abdus-Saboor, asked what such input might do in a natural social behaviour. They worked with adult female mice and a Cre line that marks the developmental Mrgprb4 lineage. Optogenetic activation of these afferents in back skin produced a conditioned place preference and a dorsiflexion resembling the lordosis posture of mating. When the lineage was ablated, females were less sexually receptive. Stimulating the lineage evoked dopamine release in the brain, and in ablated females the dopamine-sensor signal in the nucleus accumbens during mounting was reduced. The study, published in Cell in 2023, gave a measurable path from a defined set of skin afferents to a social behaviour and a central neuromodulator, in female mice, and it raised the question of which adult neurons are needed.

✓ verbatim Elias et al., Cell (2023), with Abdus-Saboor as final author.
Test yourself
Question 1 of 8 Score 0 / 0

In Löken and colleagues' 2009 study of human forearm skin, how did C-tactile afferent firing change with brush velocity?
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Every structure, slide, simulation, and clip on this page is listed below with the source it came from. None of the 3D structures is drawn by hand or by AI: each one loads by accession ID from RCSB PDB or PubChem. This panel is generated from the lesson's own data file, so what it lists is what the page loads.

Simulations

  • Brush velocity and pleasantness · Original interactive — Biochemistrypedia (Deppmann Lab).

Scientist profiles & quotes

  • Line S. Löken — Löken, Wessberg, Morrison, McGlone & Olausson, Nature Neuroscience (2009), including its author-contributions statement.
  • Håkan Olausson — Olausson et al., Nature Neuroscience (2002); Löken et al., Nature Neuroscience (2009); Marshall et al., eLife (2019), article 51642.
  • David D. Ginty — Li et al., Cell (2011); Bai et al., Cell (2015).
  • Ishmail Abdus-Saboor — Elias et al., Cell (2023), with Abdus-Saboor as final author.

Quotes are verbatim from the cited source. Profile text is original to this site and was checked against the sources cited.

Animated explainer

A Match Between Two Curves · narration: an AI narrator voice (Gemini, Charon) reading narration written from this lesson's text · animation: AI-generated in code (Manim) by Claude, a schematic with no drawn molecular structures, plots computed from their equations · captions from the narration script.

Images & figures

2 illustrations in this lesson are AI-generated: drawn by an image model from a written spec, then checked by a separate AI judge against the spec and the lesson text. None shows a chemical structure or data.

  • two skin blocks side by side. On the left a thin unsheathed C-LTMR axon ends in gold terminals running lengthwise along a hair follicle; on the right a thick myelinated Aβ field-LTMR axon ends in gold rings wrapped around a follicle. An inset shows one axon branching to a ring ending on each of five follicles while a broad arrow strokes across the hairs.
  • three panels of a two-chamber box seen from above. A mouse is first placed in one chamber while its MrgprB4 neurons are activated, then in the other chamber without activation, then left free and found in the chamber paired with activation.

Every 3D structure is rendered live from an accession ID, and every plot is drawn from its equation in the browser.

integrity Machines check the mechanics. The build confirms that every local file exists, that every question's answer key points at a real choice, and that any AI-generated scientific figure names the person who checked it; a weekly job re-resolves every accession ID against its database. Questions are original; MCAT-style items are written for this site and are not real AAMC questions. Banned sources (the Tymoczko textbook, publisher decks, copyrighted figures) are not used.

Like I'm five

Your skin has special slow nerves that like a gentle stroke, not too slow and not too fast. When someone strokes your arm at just that speed, those nerves send the most messages. People say that speed feels nicest too. Scientists are still finding out whether those nerves are why it feels nice.
High school

Hairy skin has several kinds of touch nerve. One kind in people, called C-tactile fibres, has thin, unwrapped axons that conduct slowly. Recordings show these fibres fire most when a soft brush moves at about 1 to 10 centimetres per second, and people rate that range as most pleasant. In mice, similar slow fibres respond to stroking, and turning them on can make a mouse prefer a place or change its social behaviour. But a mouse preferring a room is not the same as a person saying something feels good, and other touch fibres respond to stroking too.
College

C-tactile (CT) afferents are human low-threshold unmyelinated mechanoreceptors, most studied in hairy skin. Microneurography shows that their firing peaks for brush strokes at 1 to 10 cm/s, the range a separate cohort rated most pleasant (Löken 2009). A deafferented patient felt faint pleasant touch with insular activation (Olausson 2002), but anterolateral cordotomy left brush pleasantness intact (Marshall 2019), and sparse CTs exist in glabrous hand skin (Watkins 2021). In mice, TH-positive C-LTMRs and MrgprB4 neurons are distinct unmyelinated populations, and Aβ field-LTMRs also respond to stroking. Activating MrgprB4 or Mrgprb4-lineage afferents supports place preference, and lineage loss reduces female sexual receptivity and accumbens dopamine signals (Vrontou 2013; Elias 2023). Each is a mouse outcome, not a measure of pleasure.
Graduate

The human evidence is correlational at the level of tuning (two cohorts in Löken 2009) and lesion-constrained at the level of pathway: cordotomy disrupted pain, temperature and itch in nineteen patients without significantly changing brush pleasantness, which excludes an obligatory anterolateral route for that judgement without locating the surviving one. The group fit in that study (y = -2.07x² + 1.88x + 6.22, x = log10 velocity, R² = 0.22) peaks near 2.8 cm/s but explains little of the rating variance. In mice, causal tests use different populations and readouts: chemogenetic MrgprB4 activation and place preference in juvenile males (reinforcement or anxiolysis), Mrgprb4-lineage optogenetics, ablation, receptivity and dopamine-sensor photometry in adult females, CaV3.2 deletion in the Nav1.8 lineage and social contact in males, and a Tac1 PAG to PVH oxytocin pathway recruited by touch-like stimulation. The open question is identity. TH-positive C-LTMRs do not express MrgprB4, the 2025 Mrgprb4-lineage imaging shows mechanical and thermal responses, and Aβ field-LTMRs integrate stroking across up to 180 follicle endings. Which mouse population, if any, corresponds to the human CT afferent needs human molecular data tied to physiologically identified units.
A patient who felt only the slow fibres

In a healthy arm, a brush that excites CT afferents also excites large myelinated touch fibres, so their contributions cannot be separated by asking the person. Olausson and colleagues studied a patient who lacked large myelinated afferents. Stroking hairy skin in a way that excites CT afferents produced a faint, pleasant sensation. Functional MRI showed activation of the insular region and none detectable in primary or secondary somatosensory cortex. One patient cannot establish a pathway, but the case suggested that CT input reaches awareness as a weak, pleasant feeling rather than as a sharp sense of where and what.

— Olausson et al., Nature Neuroscience (2002).
Three fibres in the palm

CT afferents had long been thought to be absent from glabrous skin. Watkins and colleagues searched for them with microneurography in the glabrous skin of the human hand and reported three. Against the myelinated mechanoreceptors recorded, that is a ratio of about 1 to 80, and the authors estimated CT density there at around seven times lower than in hairy skin. Three units are a small sample, and the estimate carries that limit. The finding turned a categorical rule into a quantitative one: sparse, not absent.

— Watkins et al., Journal of Neurophysiology (2021).
Deaf to one hair, alert to a stroke

Bai, Lehnert and colleagues in the Ginty laboratory recorded from mouse Aβ afferents whose endings wrap around hair follicles. Moving any single hair did nothing. Indenting the skin excited them only at forces in the noxious range. Yet a gentle stroke across the skin made them fire. The anatomy offered an explanation: one neuron could form as many as 180 circumferential endings. The authors proposed that each ending is weakly sensitive and that the neuron sums them across its field, so a stroke that touches many follicles at once reaches threshold when no single hair can.

— Bai, Lehnert et al., Cell (2015).

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