Abstract
Objective
To identify microRNA biomarkers and clinical factors associated with neuropathic pain
after spinal cord injury.
Design
Cross-sectional, secondary analysis of baseline data collected from ongoing clinical
studies. Using a genome-wide microRNA screening approach, we studied differential
microRNA expression in serum from 43 adults with spinal cord injury enrolled in ongoing
clinical studies. Least squares regression was used to identify associations between
microRNA expression, clinical factors, and neuropathic pain severity.
Setting
Community-dwelling individuals with spinal cord injury.
Participants
Participants (N=43) were at least 18 years old with spinal cord injury, with 28 reporting
neuropathic pain and 15 reporting no neuropathic pain.
Interventions
Not applicable.
Main Outcome Measures
Pain presence, type, and intensity were assessed with the International Spinal Cord
Injury Pain Basic Data Set. Serum microRNA normalized deep sequencing counts were
quantified from blood samples. Participant demographic factors, injury characteristics,
medication use, and health habits were collected via questionnaire.
Results
miR-338-5p expression and history of cigarette smoking were associated with and explained
37% of the variance in neuropathic pain severity (R2=0.37, F2,18=5.31, P=.02) independent of other clinical factors. No association was identified between
miR-338-5p levels and nociceptive pain severity.
Conclusions
Our findings suggest that miR-338-5p and cigarette smoking may both play a role in
the development or maintenance of neuropathic pain after spinal cord injury. While
additional work is needed to confirm these findings, validated target analysis suggests
a neuroprotective role of miR-338-5p in modulating neuroinflammation and neuronal
apoptosis and that its downregulation may result in maladaptive neuroplastic mechanisms
contributing to neuropathic pain after spinal cord injury.
Keywords
List of abbreviations:
AIS (American Spinal Injury Association Impairment Scale), BCL2L11 (Bcl-2-like protein 11), CTGF (connective tissue growth factor), CXCR4 (chemokine (C-X-C motif) receptor 4), IL (interleukin), ISCIPBDS (International Spinal Cord Injury Pain Basic Data Set), miRNA (microRNA), PHQ-9 (Patient Health Questionnaire-9), SCI (spinal cord injury)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: October 27, 2021
Accepted:
September 7,
2021
Received in revised form:
September 2,
2021
Received:
July 26,
2021
Footnotes
Portions of this material were shared in an oral presentation to the American Spinal Injury Assocation, July 7, 2021, St. Louis, MO, and by poster presentation to the Association for Clinical and Translational Science, March 30, 2021, via live webinar with abstract publication in the Journal of Clinical and Translational Science.
Supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (90SI5015-01-00); the Department of Defense (W81XWH-10-1-1043); the National Institutes of Health's National Center for Advancing Translational Sciences (TL1R002493 and UL1TR002494); the University of Minnesota's MnDRIVE (Minnesota's Discovery, Research, and Innovation Economy) Initiative; and a Florence P. Kendall Doctoral Scholarship and Promotion of Doctoral Studies I Scholarship from the Foundation for Physical Therapy Research.
Clinical Trial Registration Nos.: NCT02533713 and NCT02946424.
Disclosures: none
Identification
Copyright
© 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
