Microstructural plasticity in nociceptive pathways after spinal cord injury

• Type of Material: Article
• Authors: Sreenath P Kyathanahally, University of Zurich; Michela Azzarito, University of Zurich; Jan Rosner, University of Zurich; Vince Calhoun, Emory University; Claudia Blaiotta, University College London; John Ashburner, University College London; Nikolaus Weiskopf, Max-Planck-Institut fur Kognitions- und Neurowissenschaften; Katja Wiech, University of Oxford; Karl Friston, University College London; Gabriel Ziegler, German Center for Neurodegenerative Disease (DZNE); Patrick Freund, University of Zurich
• Language: English
• Date: 2021-08-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jnnp-2020-325580
• Title of Journal or Parent Work: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• Volume: 92
• Issue: 8
• Start Page: 863
• End Page: 871
• Grant/Funding Information: PF reports grants from ERA-NET NEURON (hMRIofSCIno: 32NE30_173678), grants from NISCI supported by the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 681094, and supported by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0137, grants from Wings for life charity (No WFL-CH-007/14), grants from International Foundation for Research (IRP-158).; NW reports grants from European Research Council/ERC grant agreement n° 616905, grants from BMBF (01EW1711AB) in the framework of ERA-NET NEURON, grants from BRAINTRAIN European research network (Collaborative Project) supported by the European Commission (Grant agreement n° 602186), grants from NISCI supported by the European Union’s Horizon 2020 research and innovation programprogramme under the grant agreement No 681094, and supported by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0137, grants from UCL Impact Awards and Siemens Healthcare, during the conduct of the study; and The Wellcome Centre for Human Neuroimaging and Max Planck Institute for Human Cognitive and Brain Sciences have institutional research agreements with Siemens Healthcare.; PF is funded by an SNF Eccellenza Professorial Fellowship grant (PCEFP3_181362/1). VC reports NIH grants R01EB020407 and R01MH118695. KF is funded by a Wellcome Trust Principal Research Fellowship (Ref: 088130/Z/09/Z). Open access of this publication is supported by the Wellcome Trust (091593/Z/10/Z).
• Keywords: Life Sciences & Biomedicine; Psychiatry; NEUROPATHIC PAIN; ANATOMY; Clinical Neurology; Science & Technology; CLASSIFICATION; MODULATION; BRAIN; SOURCE-BASED MORPHOMETRY; Surgery; Neurosciences & Neurology

Abstract

Objective To track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury (SCI). Methods A quantitative neuroimaging approach employing a multiparametric mapping protocol was used, providing indirect measures of myelination (via contrasts such as magnetisation transfer (MT) saturation, longitudinal relaxation (R1)) and iron content (via effective transverse relaxation rate (R2∗)) was used to track microstructural changes within nociceptive pathways. In order to characterise concurrent changes along the entire neuroaxis, a combined brain and spinal cord template embedded in the statistical parametric mapping framework was used. Multivariate source-based morphometry was performed to identify naturally grouped patterns of structural variation between individuals with and without NP after SCI. Results In individuals with NP, lower R1 and MT values are evident in the primary motor cortex and dorsolateral prefrontal cortex, while increases in R2∗ are evident in the cervical cord, periaqueductal grey (PAG), thalamus and anterior cingulate cortex when compared with pain-free individuals. Lower R1 values in the PAG and greater R2∗ values in the cervical cord are associated with NP intensity. Conclusions The degree of microstructural changes across ascending and descending nociceptive pathways is critically implicated in the maintenance of NP. Tracking maladaptive plasticity unravels the intimate relationships between neurodegenerative and compensatory processes in NP states and may facilitate patient monitoring during therapeutic trials related to pain and neuroregeneration.