The identification of prognostic and diagnostic biomarkers of spinal cord injury (SCI) and SCI induced pain will
help to assign SCI patients to the correct treatment and rehabilitation regimes. Chronic neuropathic pain (NP) is
a complicated condition after a SCI that often has a lifelong and significant negative impact on life after the injury;
therefore, improved pain management is considered a significant and unmet need. NP mechanisms are hetero-
geneous and the difficulty in determining their individual contribution to specific pain types may contribute to poor
treatment outcomes in this population. The interruption of the spinothalamic pathway to the primary and secondary
sensory cortex or associated projections such as alterations of the anterior cingulate cortex and the medial and orbital
area of prefrontal cortex after SCI may result in permanent structural and functional reorganization of the brain and
spinal cord. Information about NP pathways is critical and can be used as quantitative complementary measures to
self-report qualitative pain assessments. Identifying quantitative human NP phenotypes based on multi-modal
neuroimaging and connectome measures that reflect specific spinal cord or brain mechanisms of NP is an im-
portant goal. Once a pain phenotype can be reliably replicated, its relationship with biomarkers and clinical
treatment outcomes can be analyzed, and thereby facilitate translational research and further the mechanistic
understanding of individual differences in the pain experience and in clinical trial outcomes. It also would aid in
appropriate recruitment of patients into clinical trials. The systematic characterization of structural and functional
alterations of the brain based on advanced neuroimaging techniques in people with NP following SCI has not yet
been established and development of this the long-term goal of our research agenda. Hence, the first aim of this
study is to develop multimodal brain structural and functional connectomes as well as an aggregate pain connectome
neuromatrix in uninjured control participants using advanced neuroimaging paradigms. The second aim of this study will
determine if connectomics phenotypes alter differently in SCI participants with little or mild (less than 3 on numerical
rating scale (NRS)) pain and SCI participants with moderate to severe NP. The identification of changes from the
normal connectivity of pain processing regions of the brain that underlie pain development has the potential to
uncover potential neural targets for future pain reducing therapies. As such, we aim to develop neuroimaging
biomarkers that may diagnose or predict the future development of SCI-induced pain; and finally in aim 3, we will
correlate quantitative structural-functional connectome pain neuromatrix in SCI patients with clinical pain measures.
A sub aim of this work is to unmask the relationship between allodynia, hyperalgesia and psychosocial aspects
of the pain experience after SCI. The progress regarding defining NP phenotypes may lead to more targeted
treatments such as pharmacological interventions and neuromodulation (deep brain stimulation (DBS), spinal
cord stimulation (SCS) and so on) approaches.
