Abstract

Chronic pain pathologies, which are due to maladaptive changes in the peripheral and/or central nervous systems, are debilitating diseases that affect 20% of the European adult population. A better understanding of the mechanisms underlying this pathogenesis would facilitate the identification of novel therapeutic targets. Functional connectivity (FC) extracted from coherent low-frequency hemodynamic fluctuations among cerebral networks has recently brought light on a powerful approach to study large scale brain networks and their disruptions in neurological/psychiatric disorders. Analysis of FC is classically performed on averaged signals over time, but recently, the analysis of the dynamics of FC has also provided new promising information. Keeping in mind the limitations of animal models of persistent pain but also the powerful tool they represent to improve our understanding of the neurobiological basis of chronic pain pathogenicity, this study aimed at defining the alterations in functional connectivity, in a clinically relevant animal model of sustained inflammatory pain (Adjuvant-induced Arthritis) in rats by using functional ultrasound imaging, a neuroimaging technique with a unique spatiotemporal resolution (100 μm and 2 ms) and sensitivity. Our results show profound alterations of FC in arthritic animals, such as a subpart of the somatomotor (SM) network, occurring several weeks after the beginning of the disease. Also, we demonstrate for the first time that dynamic functional connectivity assessed by ultrasound can provide quantitative and robust information on the dynamic pattern that we define as brain states. While the main state consists of an overall synchrony of hemodynamic fluctuations in the SM network, arthritic animal spend statistically more time in two other states, where the fluctuations of the primary sensory cortex of the inflamed hind paws show asynchrony with the rest of the SM network. Finally, correlating FC changes with pain behavior in individual animals suggest links between FC alterations and either the cognitive or the emotional aspects of pain. Our study introduces fUS as a new translational tool for the enhanced understanding of the dynamic pain connectome and brain plasticity in a major preclinical model of chronic pain.

Details

Title
Ultrafast ultrasound imaging pattern analysis reveals distinctive dynamic brain states and potent sub-network alterations in arthritic animals
Author
Rahal Line 1   VIAFID ORCID Logo  ; Thibaut Miguel 2 ; Rivals Isabelle 3 ; Claron Julien 4 ; Lenkei Zsolt 5 ; Sitt, Jacobo D 6 ; Tanter Mickael 7 ; Pezet Sophie 1   VIAFID ORCID Logo 

 Laboratory of Brain Plasticity, ESPCI Paris, PSL Research University, CNRS UMR 8249, 10 rue Vauquelin, Paris, France (GRID:grid.15736.36) (ISNI:0000 0001 1882 0021); Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Paris, France (GRID:grid.15736.36) 
 Laboratory of Brain Plasticity, ESPCI Paris, PSL Research University, CNRS UMR 8249, 10 rue Vauquelin, Paris, France (GRID:grid.15736.36) (ISNI:0000 0001 1882 0021) 
 Equipe de Statistique Appliquée, ESPCI Paris, PSL Research University, UMRS 1158, 10 rue Vauquelin, Paris, France (GRID:grid.15736.36) (ISNI:0000 0001 1882 0021) 
 Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Paris, France (GRID:grid.15736.36) 
 Laboratory of Brain Plasticity, ESPCI Paris, PSL Research University, CNRS UMR 8249, 10 rue Vauquelin, Paris, France (GRID:grid.15736.36) (ISNI:0000 0001 1882 0021); Center of Psychiatry and Neurosciences, INSERM U894, 102 rue de la Santé, Paris, France (GRID:grid.7429.8) (ISNI:0000000121866389) 
 Institut du Cerveau et de la Moelle, INSERM U1127, CNRS UMR 7225, Sorbonne University, UPMC Univ Paris 06 UMR, Paris, France (GRID:grid.425274.2) (ISNI:0000 0004 0620 5939) 
 Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Paris, France (GRID:grid.425274.2) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2417701502
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.