Large-scale functional brain network organization is largely preserved in neuropathic pain despite selective circuit-level adaptations

Neuropathic pain results from damage to the nervous system and causes persistent changes in brain function that contribute to chronic pain. Understanding how these changes evolve over time is essential for identifying the mechanisms that sustain the disease. Here we show how brain-wide communication changes during the development and persistence of neuropathic pain in male mice using resting-state functional ultrasound imaging in awake and anesthetized animals.

Pain onset is associated with transient increases in communication between brain regions involved in sensory, motivational, and emotional processing, whereas the persistent phase shows reduced communication within movement-related networks. Animals that undergo surgery without nerve injury also display lasting changes, revealing brain plasticity independent of neuropathic pain. Despite these network alterations, the overall organization of spontaneous brain activity remains stable.

These findings reveal phase-dependent adaptations in brain circuits while preserving global resting-state brain dynamics. This work was supported by Iconeus (S. Cazzanelli’s PhD fellowship), the ANRT (S.

Cazzanelli’s PhD fellowship), the Agence Nationale de la recherche (Project ‘PINCH’, 18-CE37-0005-01), the Institut National de la Santé et de la Recherche Médicale, CNRS, ESPCI-Paris and PSL University. Authors would like to thank Mrs L. Antoinette for animal husbandry.

Finally, this work was supported by the Inserm ART (Technology Research Accelerator) in “Biomedical Ultrasound”. Physics for Medicine Paris, INSERM, ESPCI Paris, CNRS, PSL Research University, Paris, France Silvia Cazzanelli, Samuel Le Meur-Diebolt, Jérome Baranger, Youenn Travert-Jouanneau, Alexandre Dizeux, Nathalie Ialy-Radio, Thomas Deffieux, Mickael Tanter & Sophie Pezet Silvia Cazzanelli, Samuel Le Meur-Diebolt, Luc Eglin, Adrien Bertolo, Bruno Felix Osmanski & Jeremy Ferrier Institut des Neurosciences Cellulaires et Intégratives, CNRS, University of Strasbourg, Strasbourg, France MT, TD and BFO are co-founders and shareholders of Iconeus company. MT and TD are co-inventor of several patents in the field of neurofunctional ultrasound and ultrafast ultrasound.

MT and TD do not have any other financial conflict of interest, nor any non-financial conflict of interests. SLMED, LE, AB and JF are currently employed by Iconeus. SC’s PhD was partially funded by Iconeus.