| 1. |
- Case, L. K., et al.
(författare)
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Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking A beta fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for A beta afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection. The mechanisms underlying deep pressure sensing are not fully understood. Here the authors demonstrate that while two individuals lacking A beta fibers demonstrate impaired deep pressure sensing, seven individuals with PIEZO2 loss of function mutations display normal deep pressure responses.
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| 2. |
- Nagi, Saad, et al.
(författare)
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An ultrafast system for signaling mechanical pain in human skin
- 2019
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated ("fast" pain) or unmyelinated ("slow" pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMR5) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2.These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.
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| 3. |
- Case, L. K., et al.
(författare)
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Ab-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers
- 2023
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Ingår i: Eneuro. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A prefer-ence for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway. Recently, ablation of the spinotha-lamic pathway-thought to convey all C-fiber sensations-in patients with cancer pain impaired pain, tempera-ture, and itch, but not ratings of pleasant touch. This suggested integration of afferent A and CT fiber input in the spinal cord, or mechanoreceptive A-fiber contributions to computations of touch pleasantness in the brain. However, contribution of mechanoreceptive A-fibers to touch pleasantness, in humans without pain, remains unknown. In the current, single-blinded study, we performed two types of peripheral nerve blocks in healthy adults to temporarily eliminate the contribution of A-fibers to touch perception. Our findings show that when mechanoreceptive A-fiber function is greatly diminished, the perceived intensity and pleasantness of both gen-tle stroking and deep pressure are nearly abolished. These findings demonstrate that explicit perception of the pleasantness of CT-targeted brushing and pressure both critically depend on afferent A-fibers.
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| 4. |
- Liljencrantz, Jaquette, et al.
(författare)
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Altered C-tactile processing in human dynamic tactile allodynia
- 2013
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 154:2, s. 227-234
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Tidskriftsartikel (refereegranskat)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.
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| 5. |
- Liljencrantz, J., et al.
(författare)
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Pain and touch: Roles for c-tactile afferents in pain inhibition and tactile allodynia
- 2016
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Ingår i: Affective Touch and the Neurophysiology of CT Afferents. Olausson H., Wessberg J., Morrison I., McGlone F. (eds.). - New York : Springer. - 9781493964185 ; , s. 409-420
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In humans there is a positive correlation between the pleasantness perception of soft skin stroking and the firing rate of unmyelinated C-low-threshold mechanoreceptive afferents (often abbreviated C-LTMR in animals and C-tactile and CT afferents in humans). CT-targeted touch reduces heat pain in humans suggesting that activation of the CT system modulates pain perception. This finding is supported by animal work which has shown that C-LTMRs inhibit nociceptive signaling at the spinal cord level, release a protein (TAFA4) with analgesic effects, and have positively reinforcing and anxiolytic behavioral effects. However, under pathophysiological conditions, research in mice and humans instead suggests a role for CLTMRs and CTs in tactile allodynia. There is a divergence in results with some studies pointing to CLTMRs/CTs driving tactile allodynia, whereas others suggest a modulatory role. © 2016 Springer Science+Business Media New York.
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