Reducing inflammation through delivery of lentivirus encoding for anti-inflammatory cytokines attenuates neuropathic pain after spinal cord injury

Jonghyuck Park, Joseph T. Decker, Dominique R. Smith, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Recently, many clinical trials have challenged the efficacy of current therapeutics for neuropathic pain after spinal cord injury (SCI) due to their life-threatening side-effects including addictions. Growing evidence suggests that persistent inflammatory responses after primary SCI lead to an imbalance between anti-inflammation and pro-inflammation, resulting in pathogenesis and maintenance of neuropathic pain. Conversely, a variety of data suggest that inflammation contributes to regeneration. Herein, we investigated long-term local immunomodulation using anti-inflammatory cytokine IL-10 or IL-4-encoding lentivirus delivered from multichannel bridges. Multichannel bridges provide guidance for axonal outgrowth and act as delivery vehicles. Anti-inflammatory cytokines were hypothesized to modulate the pro-nociceptive inflammatory niche and promote axonal regeneration, leading to neuropathic pain attenuation. Gene expression analyses demonstrated that IL-10 and IL-4 decreased pro-nociceptive genes expression versus control. Moreover, these factors resulted in an increased number of pro-regenerative macrophages and restoration of normal nociceptors expression pattern. Furthermore, the combination of bridges with anti-inflammatory cytokines significantly alleviated both mechanical and thermal hypersensitivity relative to control and promoted axonal regeneration. Collectively, these studies highlight that immunomodulatory strategies target multiple barriers to decrease secondary inflammation and attenuate neuropathic pain after SCI.

Original languageEnglish
Pages (from-to)88-101
Number of pages14
JournalJournal of Controlled Release
Volume290
DOIs
StatePublished - Nov 28 2018

Bibliographical note

Funding Information:
This study was supported by the National Institute of Health (R01EB005678). Authors thank Unit for laboratory Animal Medicine at University of Michigan for animal care and maintenance and Microarray core at University of Michigan for microarray analyses.

Funding Information:
This study was supported by the National Institute of Health ( R01EB005678 ). Authors thank Unit for laboratory Animal Medicine at University of Michigan for animal care and maintenance and Microarray core at University of Michigan for microarray analyses.

Publisher Copyright:
© 2018 Elsevier B.V.

Keywords

  • Anti-inflammatory cytokine
  • Gene delivery
  • Immunoengineering
  • Neuropathic pain
  • Spinal cord injury

ASJC Scopus subject areas

  • Pharmaceutical Science

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