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

Authors

Michael N. Saunders, University of Michigan-Ann Arbor
Kate V. Griffin, University of Michigan-Ann Arbor
Irina Kalashnikova, University of Kentucky
Daniel Kolpek, University of Kentucky
Dominique R. Smith, University of Michigan-Ann Arbor
Eiji Saito, University of Michigan-Ann Arbor
Brian J. Cummings, University of California, Irvine
Aileen J. Anderson, University of California, Irvine
Lonnie D. Shea, University of Michigan-Ann Arbor
Jonghyuck Park, University of KentuckyFollow

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.

Document Type

Article

Publication Date

1-1-2024

Notes/Citation Information

© 2023 International Association for the Study of Pain

Funding Information

This work was supported by the Center for Pharmaceutical Research and Innovation (CPRI, NIH P20 GM130456), the National Center for Advancing Translational Sciences (UL1 TR001998), the University of Kentucky Neuroscience Research Priority Area (NRPA 017), the National Institute of Allergy and Infectious Diseases (R01 AI148076), and the National Institute of Neurological Disorders and Stroke (R01 NS117103). M. N. Saunders is supported by NIH grant T32GM007863. K. V. Griffin is supported by National Science Foundation Graduate Research Fellowship DGE 1256260.

Repository Citation

Saunders, Michael N.; Griffin, Kate V.; Kalashnikova, Irina; Kolpek, Daniel; Smith, Dominique R.; Saito, Eiji; Cummings, Brian J.; Anderson, Aileen J.; Shea, Lonnie D.; and Park, Jonghyuck, "Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury." (2024). Pharmaceutical Sciences Faculty Publications. 209.
https://uknowledge.uky.edu/ps_facpub/209