Large-scale functional ultrasound imaging of the spinal cord reveals in-depth spatiotemporal responses of spinal nociceptive circuits in both normal and inflammatory states

Julien Claron (1) , Vincent Hingot (1) , Isabelle Rivals (2, 3) , Line Rahal (1) , Olivier Couture (1) , Thomas Deffieux (1) , Mickael Tanter (1) , Sophie Pezet (1)

1 PhysMed Paris - Physique pour la médecine
2 UMRS 1158 - Neurophysiologie Respiratoire Expérimentale et Clinique
3 ESPCI Paris - Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris

Despite a century of research on the physiology/pathophysiology of the spinal cord in chronic pain condition, the properties of the spinal cord were rarely studied at the large-scale level from a neurovascular point of view. This is mostly due to the limited spatial and/ or temporal resolution of the available techniques. Functional ultrasound imaging (fUS) is an emerging neuroimaging approach that allows, through the measurement of cerebral blood volume, the study of brain functional connectivity or functional activations with excellent spatial (100 mm) and temporal (1 msec) resolutions and a high sensitivity. The aim of this study was to increase our understanding of the spinal cord physiology through the study of the properties of spinal hemodynamic response to the natural or electrical stimulation of afferent fibers. Using a combination of fUS and ultrasound localization microscopy, the first step of this study was the fine description of the vascular structures in the rat spinal cord. Then, using either natural or electrical stimulations of different categories of afferent fibers (Ab, Ad, and C fibers), we could define the characteristics of the typical hemodynamic response of the rat spinal cord experimentally. We showed that the responses are fiber-specific, located ipsilaterally in the dorsal horn, and that they follow the somatotopy of afferent fiber entries in the dorsal horn and that the C-fiber response is an N-methyl-D-aspartate receptordependent mechanism. Finally, fUS imaging of the mesoscopic hemodynamic response induced by natural tactile stimulations revealed a potentiated response in inflammatory condition, suggesting an enhanced response to allodynic stimulations.

Mots clés: Pain fUS Neurovascular Plasticity NMDA; Pain; fUS; Neurovascular; Plasticity; NMDA; Pain fUS Neurovascular Plasticity NMDA

Domaines: Sciences de l'ingénieur [physics]

Julien Claron, Vincent Hingot, Isabelle Rivals, Line Rahal, Olivier Couture, et al.. Large-scale functional ultrasound imaging of the spinal cord reveals in-depth spatiotemporal responses of spinal nociceptive circuits in both normal and inflammatory states. Pain, 2020, 162, pp.1047 - 1059. ⟨10.1097/j.pain.0000000000002078⟩. ⟨hal-04061241⟩