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Cortico-striatal neuronal plasticity and processing of pain affect during the transition to chronic pain

English title Cortico-striatal neuronal plasticity and processing of pain affect during the transition to chronic pain
Applicant Nevian Thomas
Number 173486
Funding scheme Bilateral programmes
Research institution Institut für Physiologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.04.2018 - 31.03.2021
Approved amount 250'000.00
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Keywords (5)

striatum; pain; anterior cingulate cortex; depression; chronic pain

Lay Summary (German)

Lead
Chronische Schmerzen sind ein weitverbreitetes Krankheitsbild, das bei etwa 20% der Bevölkerung auftritt. Eine Ursache für chronische Schmerzen kann eine Verletzung des somato-sensorischen Systems sein, wie es z.B. bei peripheren Nervenlesionen oder diabetischer Neuropathie vorkommt. Diese Schmerzen werden als neuropathische Schmerzen bezeichnet.
Lay summary
Chronische Schmerzen beeinflussen den Alltag der betroffenen Patienten massgeblich und gehen häufig  mit einem Antriebsverlust, Rückzug und Depressionen einher. Aus eurobiologischer Sicht entstehen chronische Schmerzen durch langanhaltende plastische Veränderungen von Synapsen, Nervenzellen und neuronalen Netzwerken. Dadurch werden schmerzhafte Reize besser übertragen und als schmerzhafter Wahrgenommen. Gleichzeitig wird die emotionale Schmerzwahrnehmung modifiziert und die Aufmerksamkeit vermehrt auf den Schmerz gerichtet. Es wird vermutet, dass dieses auf Veränderungen des limischen und mesolimbischen Systems beruht. Wir werden bildgebende und elektrophysiologische Methoden sowie Verhaltensexperimente benutzen um einzelne Synapsen, Nervenzellen und neuronale Netzwerke zu untersuchen.
Dieses Projekt untersucht die Veränderung der neuronalen Verbindungen bei der Entstehung chronischer Schmerzen zwischen dem Gyrus Cinguli, einem Hirnareal, das für die emotionale Schmerzverarbeitung wichtig ist und den Basalganglien, die Motivation und Antrieb steuern. Dadurch soll ein besseres Verständnis über den Zusammenhang von chronischen Schmerzen und den Begleitsymptomen, wie Depression gewonnen werden. 


Direct link to Lay Summary Last update: 28.02.2018

Responsible applicant and co-applicants

Project partner

Collaboration

Group / person Country
Types of collaboration
Walter Senn, University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Fernando Kasanetz, University of Buenos Aires Argentina (South America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Matthew Larkum Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
182571 Function and plasticity of afferent inputs to the anterior cingulate cortex in chronic pain 01.09.2019 Project funding (Div. I-III)
159872 Causes and consequences of circuit remodelling by synaptic plasticity on the dynamics of cortical neuronal networks in chronic pain 01.05.2015 Project funding (Div. I-III)

Abstract

Background.Neuropathic pain caused by peripheral nerve injury is a debilitating neurological condition of high clinical relevance. On the cellular level, the elevated pain sensitivity is induced by plasticity of neuronal function along the pain pathway. Chronic neuropathic pain is characterized by unexplainable widespread pain, burning sensation, pain caused by light touch or acute pain in the absence of a noxious stimulus that can last for months. In addition to modifications in the periphery and in the spinal cord, changes in cortical areas important for the cognitive-affective processing of pain contribute to the development of neuropathic pain, including the anterior cingulate cortex (ACC), anterior insula and prefrontal cortex. Furthermore, recent evidences suggest that basal ganglia (BG) structures implicated in the motivational aspects of pain, such as the ventral tegmentral area (VTA) and the striatum may be involved in the transition from acute to chronic pain.During the last years we have investigated how neuropathic pain alters cellular, synaptic and network function of the ACC. Recent preliminary data combining cell-type specific retrograde labelling and c-fos expression suggest an enhanced activation of cortico-striatal ACC neurons after sciatic nerve damage, supporting the idea that the recruitment of the ACC cortico-BG pathway by noxius stimuli may be a key determinant for the chronification of pain.Project outlineWe would like to address the hypothesis that neuropathic pain is associated with an abnormal processing of nociceptive information in the ACC that spreads to the BG through direct cortico-striatal projections. This pathological function may result from abnormal neuronal plasticity on the ACC cortico-striatal system. Altogether, this may mediate some of the emotional consequences of chronic pain, such as exaggerated pain affect, anhedonia, anxiety and depression. To test this, we would like to investigate in detail how nociceptive information is processed in cortico-striatal microcircuits of the ACC and striatum in control conditions and after a neuropathic injury. Furthermore, we would like to study the changes in cellular and synaptic properties on ACC cortico-striatal and striatal neurons. Finally, we would like to set up a miniature portable fluorescent microscope system to image neuronal activity in freely moving animals while performing pain-induced affective-cognitive behavioural tasks. Expected value of the projectUnderstanding the neuronal plasticity mediating chronic pain is of high clinical importance because so far there are no satisfactory treatment strategies for most chronic pain syndromes. The proposed experiments will give fundamental insights into the consequences of neuropathic pain in the cortico-BG system. Also, we will gain novel insight into the brain mechanisms of pain perception.
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