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Impact of deafferentation on descending pain control systems

English title Impact of deafferentation on descending pain control systems
Applicant Curt Armin
Number 169250
Funding scheme Project funding
Research institution Zentrum für Paraplegie Universitätsklinik Balgrist
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2017 - 31.03.2021
Approved amount 429'000.00
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Keywords (6)

dorsal column function; spinothalamic tract; sensori-sensory interactions; spinal cord injury; imaging; sensory plasticity

Lay Summary (German)

Lead
Prof. Dr. Armin Curt
Lay summary

Nach einer Rückenmarksverletzung (RMV) können die afferenten Bahnen, welche Informationen bezüglich der Sensorik von der Peripherie zum Hirn leiten, beschädigt sein. Es gibt auch Hinweise dafür, dass eine RMV Veränderungen in der Verarbeitung von sensorischen Informationen von oberhalb der Läsion zur Folge hat. Diese Veränderungen werden verdächtigt, eine wichtige Rolle in der Entstehung und Aufrechterhaltung von Komplikationen des sensorischen Systems, wie neuropathischem Schmerz, zu spielen. Dieses SNF Projekt wird die durch eine RMV hervorgerufenen Veränderungen in der Verarbeitung von sensorischen Informationen untersuchen. Das Ziel ist es besser zu verstehen, wie solche Veränderungen entstehen und warum gewisse Veränderungen zu neuropathischen Schmerzen führen. Ein fundiertes Wissen bezüglich dieser Veränderungen und den zugrundeliegenden Mechanismen ist essentiell für die Entwicklung neuer Interventionen zur Behandlung dieser Veränderungen im sensorischen System. Es sind drei Projekte geplant, welche neurophysiologische und -radiologische Untersuchungsmethoden umfassen.

In Projekt 1 wird die Sensitivität und Spezifizität der kalt-evozierten Potentiale bei gesunden Kontrollen und Individuen mit einer chronischen RMV evaluiert. Anschliessend wird im Rahmen einer Längsschnittstudie die Reaktionsfähigkeit von kalt- und hitze-evozierten Potentialen bei Individuen mit einer akuten RMV bestimmt.

Das Projekt 2 untersucht die Auswirkungen der Deafferentation auf die supra-spinale und spinale endogene Fähigkeit afferenten Input zu modulieren. Dafür werden Individuen mit chronischen RMV mit gesunden Kontrollprobanden verglichen.

Das Projekt 3 hat die Absicht anhand modernster Bildgebungsverfahren Hirnbereiche zu identifizieren, die in der Modulation von afferentem Input involviert sind. Des Weiteren sollen potenzielle Veränderungen in diesen Bereichen aufgedeckt werden, welche für die veränderte Fähigkeit afferentem Input zu modulieren verantwortlich sind.
Direct link to Lay Summary Last update: 26.10.2016

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Investigation of Cerebral White Matter Changes After Spinal Cord Injury With a Measure of Fiber Density
Huynh Vincent, Staempfli Philipp, Luetolf Robin, Luechinger Roger, Curt Armin, Kollias Spyros, Hubli Michèle, Michels Lars (2021), Investigation of Cerebral White Matter Changes After Spinal Cord Injury With a Measure of Fiber Density, in Frontiers in Neurology, 12, 598336.
The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature
Sirucek Laura, Jutzeler Catherine Ruth, Rosner Jan, Schweinhardt Petra, Curt Armin, Kramer John Lawrence Kipling, Hubli Michèle (2020), The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature, in Pain Medicine, 21(11), 2839-2849.
Pinprick Evoked Potentials—Reliable Acquisition in Healthy Human Volunteers
Rosner Jan, Scheuren Paulina Simonne, Stalder Stephanie Anja, Curt Armin, Hubli Michèle (2020), Pinprick Evoked Potentials—Reliable Acquisition in Healthy Human Volunteers, in Pain Medicine, 21(4), 736-746.
Disentangling the Effects of Spinal Cord Injury and Related Neuropathic Pain on Supraspinal Neuroplasticity: A Systematic Review on Neuroimaging
Huynh Vincent, Rosner Jan, Curt Armin, Kollias Spyros, Hubli Michèle, Michels Lars (2020), Disentangling the Effects of Spinal Cord Injury and Related Neuropathic Pain on Supraspinal Neuroplasticity: A Systematic Review on Neuroimaging, in Frontiers in Neurology, 10, 1413.
Cold evoked potentials: Acquisition from cervical dermatomes
Rosner Jan, Rinert Janosch, Ernst Mario, Curt Armin, Hubli Michèle (2019), Cold evoked potentials: Acquisition from cervical dermatomes, in Neurophysiologie Clinique, 49(1), 49-57.
Not Hot, but Sharp: Dissociation of Pinprick and Heat Perception in Snake Eye Appearance Myelopathy
Rosner Jan, Hubli Michèle, Hostettler Pascal, Jutzeler Catherine R., Kramer John L. K., Curt Armin (2018), Not Hot, but Sharp: Dissociation of Pinprick and Heat Perception in Snake Eye Appearance Myelopathy, in Frontiers in Neurology, 9, 1144.

Collaboration

Group / person Country
Types of collaboration
MR-Center of the Psychiatric University Hospital and the Department of Child and Adolescent Psychiat Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Ass. Prof. John Kramer, ICORD, University of British Columbia (UBC) Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Research of the Department of Chiropractic Medicine at the Balgrist University Hospital and the Univ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SwiSCI Interest Group: Biomedical Perspective Talk given at a conference Multimodal Phenotyping of Central Neuropathic Pain 20.11.2020 Nottwil, Switzerland Lütolf Robin; Curt Armin;
ZNZ Annual Symposium 2020 Poster Endogenous pain modulation efficiency is associated with increased resting connectivity and structure of pain modulatory regions 10.09.2020 Zurich, Switzerland Huynh Vincent;
58th ISCoS Annual Scientific Meeting Talk given at a conference Brain Signature of Neuropathic Pain in Spinal Cord Injury Patients 05.11.2019 Nice, France Michels Lars; Curt Armin; Lütolf Robin; Kollias Spyros S.; Huynh Vincent;
58th ISCoS Annual Scientific Meeting Talk given at a conference Tonic Heat Pain Modulation in Chronic Neuropathic Pain following Spinal Cord Injury 05.11.2019 Nice, France Lütolf Robin; Curt Armin;
11th Congress of the European pain federation EFIC Talk given at a conference Central Sensitization in Neuropathic Pain following Spinal Cord Injury 04.09.2019 Valencia, Spain Curt Armin; Lütolf Robin;
11th Congress of the European Pain Federation (EFIC) Talk given at a conference Facilitatory and inhibitory pain mechanisms in human: methodological advances 04.09.2019 Valencia, Spain Lütolf Robin; Curt Armin;
2019 OHBM ANNUAL MEETING Poster Impact of neuropathic pain on brain connectivity in patients with spinal cord injury 09.06.2019 Rome, Italy Huynh Vincent; Kollias Spyros S.; Lütolf Robin; Michels Lars; Curt Armin;
Advanced neuroscience course - Acute to chronic pain Poster Brain Signature of Neuropathic Pain in Spinal Cord Injury Patients 01.06.2019 Venice, Italy Curt Armin; Huynh Vincent; Kollias Spyros S.; Michels Lars; Lütolf Robin;
63. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN) Talk given at a conference Characterization of spinothalamic tract lesions using multi-modal neurophysiology 28.03.2019 Freiburg, Germany Curt Armin;
CANoP Meeting - Cognitive and Affective Neuroscience of Pain Poster Brain Signature of Neuropathic Pain in Spinal Cord Injury Patients 31.01.2019 Fribourg, Switzerland Michels Lars; Huynh Vincent; Kollias Spyros S.; Lütolf Robin; Curt Armin;
ZNZ Annual Symposium 2018 Poster Conditioned pain modulation is associated with increased resting-state functional connectivity and structure of pain modulatory regions. 13.09.2018 Zurich, Switzerland Huynh Vincent; Michels Lars; Kollias Spyros S.; Curt Armin;
Neuroscience School of Advanced Studies Talk given at a conference Improved pain phenotyping in SCI patients with neuropathic pain 08.09.2018 Venice, Italy Lütolf Robin; Curt Armin;
Neurotrauma Summer School Talk given at a conference Brain Signature of Neuropathic Pain in Spinal Cord Injury Patients 01.07.2018 Glasgow, Great Britain and Northern Ireland Huynh Vincent;


Associated projects

Number Title Start Funding scheme
135558 Sensory plasticity in spinal cord injury 01.10.2011 Project funding
135558 Sensory plasticity in spinal cord injury 01.10.2011 Project funding
182803 Investigating attention and visual brain processing through neurofeedback intervention 01.06.2019 Project funding

Abstract

Changes within the sensory system following spinal cord injury (SCI) not only affect the individual specific sensory modalities, but also physiological sensori-sensory interactions across the spinal and supra-spinal system. While the previous SNF project focused on the detailed assessment of sensory impairment following SCI and how sensory functions become modulated (i.e., sensitization, habituation, temporal summation) the follow-up projects will specifically address how afferent inputs following SCI will interact with the descending pain control system. This will not be limited to address the potential input on pain (i.e., neuropathic pain) but seeks a broader understanding of the complex modulatory effect of afferent inputs on the perception of sensory stimuli and how this becomes distorted after SCI. We propose three projects focusing on alterations of the sensori-sensory interactions and the descending pain control systems following deafferentation in individuals with SCI using clinical, neurophysiological, and neuro-imaging assessments. The overall aim is to improve our understanding of how the descending control of afferent stimuli is altered in response to deafferenation (i.e., changes in the modulation of innocuous and nociceptive thermal inputs) and the evolution of changes throughout the course of disease. These projects aim at evaluating the relationship between changes in descending control following deafferenation and the development of clinically relevant sensory impairments (e.g., hypoalgesia) and complications (e.g., hyperalgesia, neuropathic pain). Central to the proposed studies is the assessment of differences in sensory modulation following SCI. Consolidated mechanistic understanding of the underlying sensory plasticity (i.e., sensory interactions at spinal and supraspinal levels) is highly relevant in the process of evaluation and design of novel therapeutic interventions in human SCI. In order to achieve this overall objective, three projects are planned that incorporate neurophysiological and neuroimaging techniques applied in healthy controls and individuals with SCI (i.e., acute and chronic stage of disease). In project 1, the specificity and sensitivity of cold-evoked potentials will be assessed in healthy controls and individuals with chronic SCI. Subsequently, in the framework of a longitudinal study in individuals with acute SCI we will investigate the responsiveness of the CEPs and CHEPs. Furthermore, the modulation of cold-evoked potentials (CEPs) by means of thermal conditioning (i.e., cold, warm, and interlaced cold/warm) will be investigate in healthy controls to reveal the impact of concomitant afferent inputs on the sensory processing. Project 2 focuses on the impact of deafferentation on the supra-spinal and spinal endogenous capacity to modulate afferent inputs will be examined in individuals with SCI (i.e., above the level of injury) compared to controls. Employing conditioning pain modulation (CPM) paradigm and the application of large fiber mediated stimulation (i.e., with TENS) will assess the interaction between CPM and non-painful afferent inputs on descending pain control. Importantly, the capacity to modulate afferent inputs following SCI will be a dynamic process that evolves from acute to chronic SCI and is likely influenced (or underlying) by the development of neuropathic pain. Lastly, project 3 intents to identify cerebral areas mediating descending inhibitory action as well as to reveal potential changes in these areas which might be responsible for the altered capacity to modulate afferent input. CPM and large A-beta fiber-mediated pain modulation will be used to engage pain control networks. The combination of structural (gray and white matter properties) with evoked brain responses, resting-state activity, and connectivity multimodal neuroimaging will provide complimentary information for elucidating mechanisms of altered sensory perceptions, which could provide future directions for treatment.
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