| 1. |
- 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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| 2. |
- Case, Laura K, et al.
(författare)
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Touch Perception Altered by Chronic Pain and by Opioid Blockade.
- 2016
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Ingår i: eNeuro. - 2373-2822. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Touch plays a significant role in human social behavior and social communication, and its rewarding nature has been suggested to involve opioids. Opioid blockade in monkeys leads to increased solicitation and receipt of grooming, suggesting heightened enjoyment of touch. We sought to study the role of endogenous opioids in perception of affective touch in healthy adults and in patients with fibromyalgia, a chronic pain condition shown to involve reduced opioid receptor availability. The pleasantness of touch has been linked to the activation of C-tactile fibers, which respond maximally to slow gentle touch and correlate with ratings of pleasantness. We administered naloxone to patients and healthy controls to directly observe the consequences of µ-opioid blockade on the perceived pleasantness and intensity of touch. We found that at baseline chronic pain patients showed a blunted distinction between slow and fast brushing for both intensity and pleasantness, suggesting reduced C-tactile touch processing. In addition, we found a differential effect of opioid blockade on touch perception in healthy subjects and pain patients. In healthy individuals, opioid blockade showed a trend toward increased ratings of touch pleasantness, while in chronic pain patients it significantly decreased ratings of touch intensity. Further, in healthy individuals, naloxone-induced increase in touch pleasantness was associated with naloxone-induced decreased preference for slow touch, suggesting a possible effect of opioid levels on processing of C-tactile fiber input. These findings suggest a role for endogenous opioids in touch processing, and provide further evidence for altered opioid functioning in chronic pain patients.
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| 3. |
- Perini, Irene, et al.
(författare)
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Mutation Carriers with Reduced C-Afferent Density Reveal Cortical Dynamics of Pain-Action Relationship during Acute Pain
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 30:9, s. 4858-4870
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Tidskriftsartikel (refereegranskat)abstract
- The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain-action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers subjective pain thresholds did not differ from controls, but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain-action integration with increased responses for task-relevant painful stimulation ("signal," requiring button-press execution) over task-irrelevant stimulation ("noise," requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices-but not the AI and mid-ACC regions-during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI-mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.
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