Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury

Michael N. Saunders, Kate V. Griffin, Irina Kalashnikova, Daniel Kolpek, Dominique R. Smith, Eiji Saito, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea, Jonghyuck Park

Research output: Contribution to journalArticlepeer-review

Abstract

Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide-co-glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion. Nanoparticles primarily reduce peripheral immune-mediated mechanisms of neuropathic pain, including neuropathic pain-associated gene transcript frequency, transient receptor potential ankyrin 1 nociceptor expression, and MCP-1 (CCL2) chemokine production in the subacute period after injury. Altered central neuropathic pain mechanisms during this period are limited to reduced innate immune cell cytokine expression. However, in the chronic phase of SCI, nanoparticle treatment induces changes in both central and peripheral neuropathic pain signaling, driving reductions in cytokine production and other immune-relevant markers. This research suggests that drug-free PLG nanoparticles reprogram peripheral proalgesic pathways subacutely after SCI to reduce neuropathic pain outcomes and improve chronic central pain signaling.

Original languageEnglish
Pages (from-to)92-101
Number of pages10
JournalPain
Volume165
Issue number1
DOIs
StatePublished - Jan 1 2024

Bibliographical note

Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.

Keywords

  • Biomaterials
  • Immunoengineering
  • Nanoparticles
  • Neuropathic pain
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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