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-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.