Project

Back to overview

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 (Div. I-III)
Research institution Paraplegikerzentrum Uniklinik 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
Show all

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

Associated projects

Number Title Start Funding scheme
135558 Sensory plasticity in spinal cord injury 01.10.2011 Project funding (Div. I-III)
135558 Sensory plasticity in spinal cord injury 01.10.2011 Project funding (Div. I-III)
182803 Investigating attention and visual brain processing through neurofeedback intervention 01.06.2019 Project funding (Div. I-III)

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.
-