Open AccessPhospholipase A2 Inhibitor-Loaded Phospholipid Micelles Abolish Neuropathic Pain
Author(s) -
Sonia Kartha,
Lesan Yan,
Meagan E. Ita,
Ahmad Amirshaghaghi,
Lijun Luo,
Yulong Wei,
Andrew Tsourkas,
Beth A. Winkelstein,
Zhiliang Cheng
Publication year - 2020
Publication title -
acs nano
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.554
H-Index - 382
eISSN - 1936-086X
pISSN - 1936-0851
DOI - 10.1021/acsnano.0c00999
Subject(s) - neuropathic pain , micelle , phospholipid , medicine , pharmacology , anesthesia , phospholipase a2 , chemistry , enzyme , biochemistry , membrane , aqueous solution
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-A 2 (sPLA 2 ) 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 sPLA 2 activity. Using a rodent model of neuropathic pain, phospholipid micelles loaded with the sPLA 2 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 sPLA 2 inhibitor-loaded micelles can be a promising anti-inflammatory nanotherapeutic for neuropathic pain treatment.