Spinal Cord Injury Pain

1st Edition - October 21, 2021
Editors: Christine N. Sang, Claire E. Hulsebosch
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 6 6 2 - 6
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 6 6 3 - 3

Spinal Cord Injury Pain presents the basis for preclinical and clinical investigations, along with strategies for new approaches in the treatment of central neuropathic pain. Con… Read more

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Spinal Cord Injury Pain presents the basis for preclinical and clinical investigations, along with strategies for new approaches in the treatment of central neuropathic pain. Contributors from the private sector and academia provide a comprehensive review of state-of-the-art research in this challenging space. Topics include Epidemiology of Chronic Pain Following SCI, experimental models and mechanisms of chronic pain in SCI, and new targets and technologies. This book serves as a resource for continued translational research that will result in novel approaches and treatments that improve function and quality of life for individuals with CNP/SCI.

Despite a better understanding of the complexity of mechanisms of CNP/SCI, improved medical and surgical management of SCI, and the subsequent acceleration of the identification of new targets and the development of novel analgesics, there is still a great unmet clinical need in the area of CNP following SCI. Hence, this book is a welcomed addition to current research and developments.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Prologue
Lessons from my central pain
A pain beyond pain
Diagnostic patterns
Eliciting symptoms
Conclusion
References
Part 1: Approaches to the development of new technologies
Chapter 1: Electrophysiological phenotyping of neuropathic pain following spinal cord injury
Abstract
Electrophysiological phenotyping of neuropathic pain following spinal cord injury
Multimodal evoked potentials—Physiological basis and clinical application
Spinothalamic tract integrity and neuropathic pain following SCI
Central sensitization and habituation of pain-related evoked responses
References
Chapter 2: Spinal cord injury pain: A retrospective
Abstract
Introduction
Classification of SCI pain
SCI pain prevalence
Neuropathic SCI pain mechanisms
Treatment of SCI pain
Conclusion
References
Chapter 3: Central neuropathic pain after spinal cord injury: Therapeutic opportunities. A brief history and temporal progression of the pathophysiology from acute trauma to chronic conditions
Abstract
Acknowledgments
Introduction
Pain terminology
Types of neuropathic pain after SCI
Modeling neuropathic pain after spinal cord injury
Pathophysiology of SCI: Contribution to the development of CNP
Future directions in clinical management of CNP after SCI
References
Chapter 4: Mechanisms of pain below the level of spinal cord injury (SCI)
Abstract
Acknowledgments
Measuring and modulating pain
Effects of morphine on a presumed response to pain
Effects of SCI on sensitivity to nociceptive stimulation
A human model of SCI pain development
Anterolateral cordotomy of monkeys
Anterolateral cordotomy of rats and SCI of humans
Spinal gray matter excitotoxicity
Remote effects of at-level spinal injury
Ischemic damage to spinal gray matter
Does at-level pain precede development of below-level pain?
Ablation of output from the superficial dorsal horn
Activation of unmyelinated (C) nocireceptive neurons
Sympathetic effects of SCI
At-level pain, below-level
Cerebral consequences of SCI
SCI, and hyperalgesia and chronic pain
The minimal spinal lesion producing below-level analgesia
Functional redundancy in spinal pathways
Effects of cordotomy on thalamic activity and activation
Below- and above-level effects associated with syringomyelia
Hyperpathic SCI pain
Interactions between afferented and deafferented neurons following SCI
Spinal transection
Spinothalamocortical systems for pain perception
Arousal by and attention to pain
Prefrontal modulation of pain; brain stem modulation of the spastic syndrome
Prospective data collection
Summary and conclusions
References
Chapter 5: Devil’s advocate: Why past and future animal models of neuropathic pain in spinal cord injury are without merit
Abstract
Neuropathic pain in humans vs animals
Neuropathic pain assessments
References
Chapter 6: Counterpoint: Animal models are indispensable for translational pain research in spinal cord injury
Abstract
Measuring pain in animals vs. humans
Animal models and mechanisms of CNP after SCI
Persistent pain vs. changes in peripheral responses
Pathophysiology of SCI that contributes to central neuropathic pain
Analgesics for clinical use discovered in animal models of CNP following SCI
The future of analgesia for CNP after SCI
References
Chapter 7: Behavioral assays of pain in rodent models of spinal cord injury
Abstract
Can pain be measured objectively?
Considerations in measuring “pain” behavior
Measures of pain behavior after SCI
Mechanical nociceptive assessments
Thermal nociceptive assessments
Nonreflexive pain tests
Nonstimulus evoked pain tests
Conclusions
References
Chapter 8: Biomarker signatures for neuropathic pain after SCI
Abstract
Introduction
Candidate biomarkers
Clinical relevance
References
Chapter 9: Decoding nociception in the spinal cord: Computer modeling and machine learning
Abstract
Introduction
Clinical assessment of SCI
Imaging and electrophysiology
Development of a spinal cord computational model for outcome prediction in SCI
Summary
References
Chapter 10: EEG biomarkers of pain and applications of machine learning
Abstract
Background
Central neuropathic pain: Neuroimaging biomarkers based on cohort analysis
Pain neuroimaging biomarkers based on machine learning
Conclusion
References
Chapter 11: Perspectives on preclinical evidence for translation in SCI
Abstract
Systematic scientific pursuits and urgent clinical needs
An early translational experience in spinal cord repair
Syringomyelia, spasticity, and neuropathic pain
Post-SCI pain and translation of cell-based strategies
Considerations for developing a translational pathway for spinal cord injury
Preclinical design for CNP: A proposal
Closing remarks
References
Chapter 12: Screening and treatment of neuropathic pain after SCI
Abstract
Introduction
Screening and diagnosis of pain after SCI
Treatment of neuropathic pain after SCI
Conclusion
References
Part 2: Mechanisms of CNP following SCI
Section 1: Spinal and supraspinal mechanisms
Chapter 13: Spinal GABA mechanism in neuropathic pain after spinal cord injury
Abstract
Introduction
GABA synthesis and reuptake
GABA receptors
GABAergic synapses
GABA and neuropathic pain after SCI
Hypofunctional GABAergic output on SCI pain
Summary
References
Chapter 14: Glial activation and neuropathic pain
Abstract
Introduction
Glial activation after SCI
Glial contribution to altered synaptic structures after SCI
Involvement of tripartite synapses in SCI-induced neuropathic pain
Neuronal-glial signaling modulates synaptic transmission after SCI
Intracellular signaling cascades in the postsynaptic neurons at tripartite synapses after SCI
Conclusion
References
Chapter 15: Mechanisms of CNP following SCI: Chemokines in neuronal-glial cell interaction
Abstract
Spinal cord injury and chronic central pain
Postlesional neuroinflammation—A trigger of CNP development
Neuron-glia interactions after nerve lesion promote and maintain CNP
Inflammatory molecules of secondary lesion cascades are involved in cell communication underlying CNP development
Chemokines and their receptors
Chemokines in neuron-glia interaction underlying neuropathic pain development
CCL2/CCR2-mediated astrocyte-neuron interaction and neuropathic pain development
Potential role of CCL21 neuron-microglia interaction in CNP development after SCI
Potential CCL3-CCR1 microglia-neuron interaction after SCI
Conclusion
References
Section 2: Peripheral mechanisms
Chapter 16: When soft touch hurts: How hugs become painful after spinal cord injury
Abstract
Neuropathic pain occurs with spinal cord injury
Cutaneous nociception
Primary sensory neurons: Detect and relay
Molecular transducers of sensory stimuli
Keratinocytes are required for normal somatosensation
Mechanisms of SCI neuropathic pain
Could skin cells contribute to the neuropathic pain experienced in SCI?
References
Chapter 17: Peripheral mechanisms contributing to central neuropathic pain following SCI
Abstract
Acknowledgments
SCI-induced growth of nociceptor fibers in the spinal cord
SCI-induced hyperactivity in nociceptors
Contribution of nociceptor hyperactivity to persistent SCI-induced pain
Biophysical mechanisms of SCI-induced nociceptor hyperexcitability
Cell signaling mechanisms that maintain SCI-induced nociceptor hyperexcitability
How does SCI induce a persistent hyperactive state in nociceptors?
Why does SCI recruit a persistent hyperactive state in nociceptors?
References
Section 3: Clinical applications of novel targets
Chapter 18: Human neural stem cell transplantation for improved recovery after spinal cord injury
Abstract
Introduction
Neural stem cells
Future work
Conclusion
References
Chapter 19: Cell transplantation for reducing neuropathic pain after SCI
Abstract
Background
Cell transplantation for neuropathic pain: Mini-pumps
Cell transplantation for neuropathic pain: Restoration of inhibitory neural circuitry
Future directions
References
Chapter 20: Gene therapy of neuropathic pain after spinal cord injury
Abstract
Introduction
Gene therapy, vehicle-free
Gene therapy by viral vectors
Gene therapy by nonviral vectors
Gene therapy by cellular vehicle
Summary
Future directions
References
Chapter 21: Exercise as a therapeutic intervention for neuropathic pain after spinal cord injury
Abstract
Introduction
Post-SCI neuropathic pain
Exercise as a therapeutic intervention post-SCI
Acute treatment strategies to prevent the onset of neuropathic pain
Delayed treatment strategies to reduce or eliminate existing neuropathic pain
How might exercise be working to reduce or prevent neuropathic pain?
Human SCI, neuropathic pain and exercise
References
Epilogue
Index

Christine N. Sang

Christine Sang, MD, MPH is Associate Professor of Anaesthesia at Harvard Medical School. Dr. Sang served as Associate Medical Director of the Pain Research Clinic at the NIH, Director of the Clinical Trials Program at the Massachusetts General Hospital Pain Center, and is currently the Director of the Translational Pain Research Program at the Brigham and Women's Hospital (BWH). She has served on several committees including the American Pain Society (as director-at-large), American Society of Anesthesiologists (as a member of the chronic pain analgesic guidelines committee), American College of Occupational and Environmental Medicine (as a member of the chronic pain practice guidelines committee), the National Spinal Cord Injury Association/United Spinal Association (as founding chairman of its Medical and Scientific Advisory Committee), North American Clinical Trial Network Neurological Outcomes Assessment Task Force, the Rick Hansen Institute (as director), the Healthcare Institute for National Renewal and Innovation (director), and several local advisory committees including the NIH-funded Harvard University Catalyst, the BWH Clinical Investigation Advisory Committee, the BWH Translational Accelerator Advisory Committee, and the BWH Research Management Task Force. Dr. Sang has specific expertise in the development of innovative clinical trial strategies to accelerate the clinical development of novel analgesics. These include new clinical trial methodologies (in Phase 1a/First-in-Human through to Phase 2a clinical trials) and the discovery of potential clinical biomarkers to to target selective mechanisms of pain by optimizing efficient designs, endpoints (including biomarkers), and execution.

Affiliations and expertise

Associate Professor of Anesthesia, Harvard Medical School, Boston, MA, USA

Claire E. Hulsebosch

Claire E. Hulsebosch, Ph.D. is Professor, Department of Neurobiology and Anatomy, McGovern Medical School, The University of Texas Health Science Center at Houston. She pioneered the concept of nerve cell process reorganization and the formation of new nerve connections (synaptogenesis) in the spinal cord after injury, which formed the basis for the subsequent hypotheses involving spinal cord reorganization resulting in central neuropathic pain. She has numerous publications that demonstrate the ability of nerve cells to reorganize after spinal cord injury. In addition, she has several publications examining the ability of nerve fibers to reorganize after brain injury and stroke. Currently, Dr. Hulsebosch is part of the scientific advisory board for both the Neurological Recovery Network and the North American Clinical Trials Network, which are actively involved in advancing clinical trials in spinal cord injury. She serves as scientific advisor to the National Institute of Health for Neuroscience Initiatives, on study section for National Institute of Neurological Diseases and Stroke, on the Craig Neilsen Foundation, the Christopher and Dana Reeves Foundation, the New Jersey Commission for Spinal Cord Injury Research, The Kentucky Initiative for Brain and Spinal Cord Injury Research, The New York Commission for Spinal Cord injury Research and a variety of editorial and review boards for scientific journals. She was a founder and served as Director of Mission Connect, a multi-institutional research group whose mission is to advance research for recovery after brain and spinal cord injury, from 2005 to 2008.

Affiliations and expertise

Professor, Department of Neurobiology and Anatomy, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA