scholarly journals MrgprC11+ sensory neurons mediate glabrous skin itch

2021 ◽  
Vol 118 (15) ◽  
pp. e2022874118
Author(s):  
Haley R. Steele ◽  
Yanyan Xing ◽  
Yuyan Zhu ◽  
Henry B. Hilley ◽  
Katy Lawson ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Glabrous Skin ◽  
Limited Attention ◽  
Medical Conditions ◽  
Behavioral Assay ◽  
Hairy Skin ◽  
Itch Sensation

Itch arising from glabrous skin (palms and soles) has attracted limited attention within the field due to the lack of methodology. This is despite glabrous itch arising from many medical conditions such as plantar and palmar psoriasis, dyshidrosis, and cholestasis. Therefore, we developed a mouse glabrous skin behavioral assay to investigate the contribution of three previously identified pruriceptive neurons in glabrous skin itch. Our results show that MrgprA3+ and MrgprD+ neurons, although key mediators for hairy skin itch, do not play important roles in glabrous skin itch, demonstrating a mechanistic difference in itch sensation between hairy and glabrous skin. We found that MrgprC11+ neurons are the major mediators for glabrous skin itch. Activation of MrgprC11+ neurons induced glabrous skin itch, while ablation of MrgprC11+ neurons reduced both acute and chronic glabrous skin itch. Our study provides insights into the mechanisms of itch and opens up new avenues for future glabrous skin itch research.

scholarly journals Specialized mechanoreceptor systems in rodent glabrous skin

2018 ◽  
Author(s):  
Jan Walcher ◽  
Julia Ojeda-Alonso ◽  
Julia Haseleu ◽  
Maria K. Oosthuizen ◽  
Ashlee H. Rowe ◽  
...  
Keyword(s):  
Small Group ◽  
Rodent Species ◽  
Glabrous Skin ◽  
Skin Area ◽  
Mechanical Stimuli ◽  
Orientation Sensitivity ◽  
Hairy Skin ◽  
Physiological Properties ◽  
Sensory Fibers ◽  
Very High

AbstractRodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non-existent in the mouse. Here we developed a preparation to record from single sensory fibers of the forepaw and compared anatomical and physiological receptor properties to those of the hind paw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; >3 fold more than hind paw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissner’s corpuscles of the forepaw were several-fold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hind paw glabrous skin. All other mechanoreceptors types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D-hair receptor innervating a small group of hairs in the middle of the hind paw glabrous skin in mice. Glabrous D-hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D-hair receptors. Glabrous D-hair receptors do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration.

scholarly journals Molecular signature of pruriceptive MrgprA3+ neurons

2019 ◽  
Author(s):  
Yanyan Xing ◽  
Junyu Chen ◽  
Henry Hilley ◽  
Haley Steele ◽  
Jingjing Yang ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Molecular Signature ◽  
Neuronal Populations ◽  
Pathological Conditions ◽  
Chronic Itch ◽  
Itch Sensation ◽  
Profile Changes ◽  
Allergic Contact

ABSTRACTItch, initiated by the activation of sensory neurons, is frequently associated with dermatological or systemic diseases and significantly affects patient quality of life. MrgprA3+ sensory neurons have been identified as one of the major itch-sensing neuronal populations. Mounting evidence has demonstrated that peripheral pathological conditions induce physiological regulations of sensory neurons, which is critical for the maintenance of chronic itch sensation. However, the underlying molecular mechanisms are not clear. Here we performed RNA sequencing of genetically labeled MrgprA3+ neurons under both naïve and allergic contact dermatitis condition. Our results revealed the unique molecular signature of itch-sensing neurons and the distinct transcriptional profile changes that result in response to dermatitis. We found enrichment of nine Mrgpr family members and two histamine receptors in MrgprA3+ neurons, suggesting that MrgprA3+ neurons are the main, direct neuronal target for histamine and Mrgprs agonists. In addition, Ptpn6 and Pcdh12 were identified as novel and highly selective markers of MrgprA3+ neurons. We also discovered that MrgprA3+ neurons respond to skin dermatitis in a way that is unique from other sensory neurons by regulating a combination of transcriptional factors, ion channels, and key molecules involved in synaptic transmission. These results significantly increase our knowledge of itch transmission and uncover potentially novel targets for combating itch.

scholarly journals Tiling and somatotopic alignment of mammalian low-threshold mechanoreceptors

2019 ◽  
Vol 116 (19) ◽  
pp. 9168-9177 ◽  
Author(s):  
Emily D. Kuehn ◽  
Shan Meltzer ◽  
Victoria E. Abraira ◽  
Cheng-Ying Ho ◽  
David D. Ginty
Keyword(s):  
Spinal Cord ◽  
Sensory Neurons ◽  
Hair Follicles ◽  
Mechanical Stimuli ◽  
Central Projections ◽  
Axonal Projections ◽  
Hairy Skin ◽  
Static Indentation ◽  
Innervation Patterns ◽  
Low Threshold

Innocuous mechanical stimuli acting on the skin are detected by sensory neurons, known as low-threshold mechanoreceptors (LTMRs). LTMRs are classified based on their response properties, action potential conduction velocity, rate of adaptation to static indentation of the skin, and terminal anatomy. Here, we report organizational properties of the cutaneous and central axonal projections of the five principal hairy skin LTMR subtypes. We find that axons of neurons within a particular LTMR class are largely nonoverlapping with respect to their cutaneous end organs (e.g., hair follicles), with Aβ rapidly adapting-LTMRs being the sole exception. Individual neurons of each LTMR class are mostly nonoverlapping with respect to their associated hair follicles, with the notable exception of C-LTMRs, which exhibit multiple branches that redundantly innervate individual hair follicles. In the spinal cord, LTMR central projections exhibit rostrocaudal elongation and mediolateral compression, compared with their cutaneous innervation patterns, and these central projections also exhibit a fine degree of homotypic topographic adjacency. These findings thus reveal homotypic tiling of LTMR subtype axonal projections in hairy skin and a remarkable degree of spatial precision of spinal cord axonal termination patterns, suggesting a somatotopically precise tactile encoding capability of the mechanosensory dorsal horn.

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

2020 ◽  
Author(s):  
Roger H Watkins ◽  
Mariama Dione ◽  
Rochelle Ackerley ◽  
Helena Backlund Wasling ◽  
Johan Wessberg ◽  
...  
Keyword(s):  
Firing Frequency ◽  
Glabrous Skin ◽  
Whole Body ◽  
Human Hand ◽  
Hairy Skin ◽  
Ct Afferents ◽  
Touch Perception ◽  
The Face ◽  
Nerve Recordings ◽  
Future Work

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.

scholarly journals Stress-Induced Mast Cell Activation in Glabrous and Hairy Skin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Constantin Căruntu ◽  
Daniel Boda ◽  
Sorin Musat ◽  
Ana Căruntu ◽  
Eugen Mandache
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Prolonged Exposure ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Glabrous Skin ◽  
Stress Exposure ◽  
Hairy Skin ◽  
The Impact

Mast cells play a key role in modulation of stress-induced cutaneous inflammation. In this study we investigate the impact of repeated exposure to stress on mast cell degranulation, in both hairy and glabrous skin. Adult male Wistar rats were randomly divided into four groups: Stress 1 day(n=8), Stress 10 days(n=7), Stress 21 days(n=6), and Control(n=8). Rats in the stress groups were subjected to 2 h/day restraint stress. Subsequently, glabrous and hairy skin samples from animals of all groups were collected to assess mast cell degranulation by histochemistry and transmission electron microscopy. The impact of stress on mast cell degranulation was different depending on the type of skin and duration of stress exposure. Short-term stress exposure induced an amplification of mast cell degranulation in hairy skin that was maintained after prolonged exposure to stress. In glabrous skin, even though acute stress exposure had a profound stimulating effect on mast cell degranulation, it diminished progressively with long-term exposure to stress. The results of our study reinforce the view that mast cells are active players in modulating skin responses to stress and contribute to further understanding of pathophysiological mechanisms involved in stress-induced initiation or exacerbation of cutaneous inflammatory processes.

Vibrotactile Frequency Discrimination in Human Hairy Skin

2006 ◽  
Vol 95 (3) ◽  
pp. 1442-1450 ◽  
Author(s):  
D. A. Mahns ◽  
N. M. Perkins ◽  
V. Sahai ◽  
L. Robinson ◽  
M. J. Rowe
Keyword(s):  
Detection Threshold ◽  
Weber Fraction ◽  
Frequency Discrimination ◽  
Glabrous Skin ◽  
Striking Similarity ◽  
Discriminative Performance ◽  
Detection Thresholds ◽  
Low Frequencies ◽  
Hairy Skin ◽  
Finger Tip

The human capacity for vibrotactile frequency discrimination has been compared directly for glabrous and hairy skin regions by means of a two-alternative, forced-choice psychophysical procedure in five subjects. Sinusoidal vibratory stimuli, delivered by means of a 4-mm-diam probe, were first used to obtain detection threshold values for the two skin sites, the finger tip and the dorsal forearm, at four standard frequencies, 20, 50, 100, and 200 Hz. Values confirmed previous results showing detection thresholds were markedly higher on hairy skin than on glabrous skin. For the discrimination task, each standard frequency, at an amplitude four times detection threshold, was paired with a series of comparison frequencies, and discrimination capacity then was quantified by deriving from psychometric function curves, measures of the discriminable frequency increment (Δƒ) and the Weber Fraction (Δƒ/ƒ), which, when plotted as a function of the four standard frequencies, revealed similar capacities for frequency discrimination at the two skin sites at the standard frequencies of 20, 100, and 200 Hz but an equivocal difference at 50 Hz. Cutaneous local anesthesia produced a marked impairment in vibrotactile detection and discrimination at the low standard frequencies of 20 and 50 Hz but little effect at higher frequencies. In summary, the results reveal, first, a striking similarity in vibrotactile discriminative performance in hairy and glabrous skin despite marked differences in detection thresholds for the two sites, and, second, the results confirm that vibrotactile detection and discrimination in hairy skin depend on superficial receptors at low frequencies but depend on deep, probably Pacinian corpuscle, receptors for high frequencies.

Receptive Properties of Mouse Sensory Neurons Innervating Hairy Skin

1997 ◽  
Vol 78 (4) ◽  
pp. 1841-1850 ◽  
Author(s):  
Martin Koltzenburg ◽  
Cheryl L. Stucky ◽  
Gary R. Lewin
Keyword(s):  
Sensory Neurons ◽  
Action Potentials ◽  
Hair Follicles ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Stimulus Response ◽  
Myelinated Fibers ◽  
C Fibers ◽  
Hairy Skin ◽  
Afferent Fibers

Koltzenburg, Martin, Cheryl L. Stucky, and Gary R. Lewin. Receptive properties of mouse sensory neurons innervating hairy skin. J. Neurophysiol. 78: 1841–1850, 1997. Using an in vitro nerve skin preparation and controlled mechanical or thermal stimuli, we analyzed the receptive properties of 277 mechanosensitive single primary afferents with myelinated ( n = 251) or unmyelinated ( n = 26) axons innervating the hairy skin in adult or 2-wk-old mice. Afferents were recorded from small filaments of either sural or saphenous nerves in an outbred mice strain or in the inbred Balb/c strain. On the basis of their receptive properties and conduction velocity, several receptor types could be distinguished. In adult animals (>6 wk old), 54% of the large myelinated fibers (Aβ, n = 83) showed rapidly adapting (RA) discharges to constant force stimuli and probably innervated hair follicles, whereas 46% displayed a slowly adapting (SA) response and probably innervated Merkel cells in touch domes. Among thin myelinated fibers (Aδ, n = 91), 34% were sensitive D hair receptors and 66% were high-threshold mechanoreceptors (AM fibers). Unmyelinated fibers had high mechanical thresholds and nociceptive functions. All receptor types had characteristic stimulus-response functions to suprathreshold force stimuli. Noxious heat stimuli (15-s ramp from 32 to 47°C measured at the corium side of the skin) excited 26% (5 of 19) of AM fibers with a threshold of 42.5 ± 1.4°C (mean ± SE) and an average discharge of 15.8 ± 9.7 action potentials and 41% (7 of 17) C fibers with a mean threshold of 37.6 ± 1.9°C and an average discharge of 22.0 ± 6.0 action potentials. Noxious cold stimuli activated 1 of 10 AM fibers and 3 of 10 C fibers. One of 10 C units responded to both heat and cold stimuli. All types of afferent fibers present in adult mice could readily be recognized in mice at postnatal day 14. However, fibers had reduced conduction velocities and the stimulus-response function to mechanical stimuli was more shallow in all fibers except for the D hairs. In juvenile mice, 22% of RA units also displayed an SA response at high stimulus intensities; these units were termed RA/SA units. We conclude that all types of cutaneous afferent fibers are already committed to their phenotype 2 wk after birth but undergo some maturation over the following weeks. This preparation has great potential for the study of transgenic mice with targeted mutations of genes that code factors that are involved in the specification of sensory neuron phenotypes.

scholarly journals Thermosensory micromapping of warm and cold sensitivity across glabrous and hairy skin of male and female hands and feet

2018 ◽  
Vol 125 (3) ◽  
pp. 723-736 ◽  
Author(s):  
Davide Filingeri ◽  
Hui Zhang ◽  
Edward A. Arens
Keyword(s):  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Protective Clothing ◽  
Glabrous Skin ◽  
Cold Sensitivity ◽  
Men And Women ◽  
Hairy Skin ◽  
Topographical Distribution ◽  
Hands And Feet

The ability of hands and feet to convey skin thermal sensations is an important contributor to our experience of the surrounding world. Surprisingly, the detailed topographical distribution of warm and cold thermosensitivity across hands and feet has not been mapped, although sensitivity maps exist for touch and pain. Using a recently developed quantitative sensory test, we mapped warm and cold thermosensitivity of 103 skin sites over glabrous and hairy skin of hands and feet in male (M; 30.2 ± 5.8 yr) and female (F; 27.7 ± 5.1 yr) adults matched for body surface area (M: 1.77 ± 0.2 m2; F: 1.64 ± 0.1 m2; P = 0.155). Findings indicated that warm and cold thermosensitivity varies by fivefold across glabrous and hairy skin of hands and feet and that hands (warm/cold sensitivity: 1.25/2.14 vote/°C) are twice as sensitive as the feet (warm/cold sensitivity: 0.51/0.99 vote/°C). Opposite to what is known for touch and pain sensitivity, we observed a characteristic distal-to-proximal increase in thermosensitivity over both hairy and glabrous skin (i.e., from fingers and toes to body of hands and feet), and found that hairy skin is more sensitive than glabrous. Finally, we show that body surface area-matched men and women presented small differences in thermosensitivity and that these differences are constrained to glabrous skin only. Our high-density thermosensory micromapping provides the most detailed thermosensitivity maps of hands and feet in young adults available to date. These maps offer a window into peripheral and central mechanisms of thermosensory integration in humans and will help guide future developments in smart skin and sensory neuroprostheses, in wearable, energy-efficient personal comfort systems, and in sport and protective clothing. NEW & NOTEWORTHY We provide the most detailed thermosensitivity maps across glabrous and hairy skin of hands and feet in men and women available to date. Our maps show that thermosensitivity varies by fivefold across hands and feet, distal regions (e.g., fingers, toes) are less sensitive than proximal (e.g., palm, sole), hands are twice as sensitive as feet, and men and women present small thermosensitivity differences. These findings will help guide developments in sensory neuroprostheses, wearable comfort systems, and sport/protective clothing.

scholarly journals A Virtual Reality Application of the Rubber Hand Illusion Induced by Ultrasonic Mid-air Haptic Stimulation

2022 ◽  
Vol 19 (1) ◽  
pp. 1-19
Author(s):  
Anca Salagean ◽  
Jacob Hadnett-Hunter ◽  
Daniel J. Finnegan ◽  
Alexandra A. De Sousa ◽  
Michael J. Proulx
Keyword(s):  
Virtual Reality ◽  
Haptic Feedback ◽  
Dorsal Surface ◽  
Glabrous Skin ◽  
Body Ownership ◽  
Virtual Hand ◽  
Hairy Skin ◽  
Palmar Surface ◽  
Hairless Skin ◽  
Ultrasonic Stimulation

Ultrasonic mid-air haptic technologies, which provide haptic feedback through airwaves produced using ultrasound, could be employed to investigate the sense of body ownership and immersion in virtual reality (VR) by inducing the virtual hand illusion (VHI). Ultrasonic mid-air haptic perception has solely been investigated for glabrous (hairless) skin, which has higher tactile sensitivity than hairy skin. In contrast, the VHI paradigm typically targets hairy skin without comparisons to glabrous skin. The aim of this article was to investigate illusory body ownership, the applicability of ultrasonic mid-air haptics, and perceived immersion in VR using the VHI. Fifty participants viewed a virtual hand being stroked by a feather synchronously and asynchronously with the ultrasonic stimulation applied to the glabrous skin on the palmar surface and the hairy skin on the dorsal surface of their hands. Questionnaire responses revealed that synchronous stimulation induced a stronger VHI than asynchronous stimulation. In synchronous conditions, the VHI was stronger for palmar stimulation than dorsal stimulation. The ultrasonic stimulation was also perceived as more intense on the palmar surface compared to the dorsal surface. Perceived immersion was not related to illusory body ownership per se but was enhanced by the provision of synchronous stimulation.

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