Phospholipase A2 Inhibitor-Loaded Phospholipid Micelles Abolish Neuropathic Pain

Treating persistent neuropathic pain remains a major clinical challenge. Current conventional treatment approaches carry a substantial risk of toxicity and provide only transient pain relief. In this work, we show that the activity and expression of the inflammatory mediator secretory phospholipase-...

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Published inACS nano Vol. 14; no. 7; pp. 8103 - 8115
Main Authors Kartha, Sonia, Yan, Lesan, Ita, Meagan E, Amirshaghaghi, Ahmad, Luo, Lijun, Wei, Yulong, Tsourkas, Andrew, Winkelstein, Beth A, Cheng, Zhiliang
Format Journal Article
LanguageEnglish
Published American Chemical Society 28.07.2020
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Summary:Treating persistent neuropathic pain remains a major clinical challenge. Current conventional treatment approaches carry a substantial risk of toxicity and provide only transient pain relief. In this work, we show that the activity and expression of the inflammatory mediator secretory phospholipase-A2 (sPLA2) enzyme increases in the spinal cord after painful nerve root compression. We then develop phospholipid micelle-based nanoparticles that release their payload in response to sPLA2 activity. Using a rodent model of neuropathic pain, phospholipid micelles loaded with the sPLA2 inhibitor, thioetheramide-PC (TEA-PC), are administered either locally or intravenously at the time of painful injury or 1–2 days afterward. Local micelle administration immediately after compression prevents pain for up to 7 days. Delayed intravenous administration of the micelles attenuates existing pain. These findings suggest that sPLA2 inhibitor-loaded micelles can be a promising anti-inflammatory nanotherapeutic for neuropathic pain treatment.
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S.K. and Z.C. conceived and performed all designs, experiments, and characterization in this study, as well as prepared the manuscript and figures. L.Y. and A.A. prepared and characterized the nanoparticles. M.I. performed in vitro cytotoxicity experiments. L.L. collected blood and determined the circulation time of the nanoparticles. W.Y. performed the organ toxicity study. A.T., B.W., and Z.C. conceived and oversaw all aspects of this study and prepared the manuscript.
Author Contributions
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.0c00999