Phospholipase A2 Inhibitor-Loaded Phospholipid Micelles Abolish Neuropathic Pain

• Published in: ACS 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
• Language: English
• Published: American Chemical Society 28.07.2020
• Subjects: phospholipase; neuropathic pain; inhibitor; phospholipid micelles; inflammation
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.0c00999

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.