Cerebral palsy (CP) is one of the most prevalent and costly pediatric neurologic conditions diagnosed in the United States. Although the brain injuries seen in these children are non-progressive, they often instigate a cascade of structural (i.e., boney malalignments, muscular contractures) and functional (i.e., co-contractions, spasticity) abnormalities within the musculoskeletal system that can become worse throughout development. These secondary changes are presumed to be primarily responsible for the chronic musculoskeletal pain that is seen in a large percentage of children with CP. However, currently there is a major lack of knowledge in this area, especially in regard to the neurophysiological mechanisms of the persistent pain, as most studies to date have focused on quantifying the prevalence of pain symptoms and not the underlying physiology. Without this critical information, the prevention, treatment and evaluation of the chronic musculoskeletal pain will not advance. Our extensive magnetoencephalographic (MEG) brain imaging program has identified that the early brain insults experienced by children with CP result in aberrant processing of the peripheral sensations by the somatosensory cortices. Recently, we have extended these results by showing that children with CP who have more abnormal somatosensory cortical oscillations following peripheral stimulation of the feet, also have higher reported pain. This relationship implies that there might be a fundamental link between the integrity of somatosensory cortical processing and the pain perceptions of children with CP. The goal of this proposal is to test our scientific premise that the disturbed somatosensory neural connections, potentially arising from maladaptive neuroplastic changes following early brain injuries, are altered in children with CP and that this leads to heightened activity in the pain perception network and chronic pain. Our approach is of ?high risk?, but has the potential to be remarkably ?rewarding,? as it may lead to novel insights and a paradigm shift in our understanding of pain perception in children with CP.
The Specific Aims of this proposal will (1) demonstrate that the strength of somatosensory cortical oscillations following peripheral stimulation of the mechano- and nociceptors of the feet and hands will scale with a child?s perceived pain levels, and (2) determine if the strength of somatosensory cortical oscillations following peripheral stimulation are differentially altered in children with CP who have low versus high pain levels, and whether both groups differ from typically-developing (TD) children. Briefly, our study will use MEG, advanced image reconstruction methods, and time series analysis to quantify the strength of somatosensory cortical oscillations following stimulation of peripheral mechano- and nociceptors in TD children, and children who have spastic diplegic CP and different pain levels (i.e., severity). Achieving our Aims will provide substantial insight on the neural basis of chronic pain in children with CP, and may spark a paradigm shift in the mainstream treatment and assessment of musculoskeletal pain in this population.

Public Health Relevance

Despite the alarming number of children with cerebral palsy (CP) that report chronic musculoskeletal pain, it is often overlooked in the clinic because of the uncertainty surrounding its origin, and how to best assess and treat the pain. This proposal will use brain imaging to test our scientific premise that the heightened pain perceptions in children with CP are at least partly a result of maladaptive processing of peripheral information within somatosensory cortices. Support for this hypothesis has the potential to dramatically alter the field?s understanding of pain in children with CP, and ultimately lead to major changes in the treatment and assessment of musculoskeletal pain in children with CP.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD096390-01A1
Application #
9745914
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Marden, Susan F
Project Start
2019-04-01
Project End
2021-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198