miR-338-5p Levels and Cigarette Smoking are Associated With Neuropathic Pain Severity in Individuals With Spinal Cord Injury: Preliminary Findings From a Genome-Wide microRNA Expression Profiling Screen

Jesse L. Kowalski, Nguyen M Nguyen, Ricardo A. Battaglino, Scott P. Falci, Susan Charlifue, Leslie R. Morse

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)738-746
Number of pages9
JournalArchives of Physical Medicine and Rehabilitation
Volume103
Issue number4
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2021 The American Congress of Rehabilitation Medicine

Keywords

  • MicroRNAs
  • Neuralgia
  • Rehabilitation
  • Smoking
  • Spinal cord injuries
  • Tobacco products

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