Phospholipase A<sub>2</sub> Inhibitor-Loaded Phospholipid Micelles Abolish Neuropathic Pain
Sonia Kartha, Lesan Yan, Meagan E. Ita, Ahmad Amirshaghaghi, Lijun Luo, Yulong Wei, Andrew Tsourkas, Beth A. Winkelstein, Zhiliang Cheng
Abstract
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.