Project Grant R61NS149953

The National Institute of Neurological Disorders and Stroke awarded Massachusetts General Hospital $1.130557 million on August 20, 2026, under the Drug Use and Addiction Research Programs (CFDA 93.279) to develop a non-viral lipid nanoparticle-delivered gene therapy for acute pain treatment as an alternative to opioids.

The project focuses on creating a focal-delivery, non-opioid therapeutic targeting postsurgical pain as the primary indication, with secondary applications to acute exacerbations of chronic pain. The R61 phase of this translational R61/R33 proposal evaluates lipid nanoparticle formulation components to achieve nociceptor-selective delivery and temporary reduction in nociceptor excitability. Work includes measuring payload delivery specificity, duration, off-target accumulation in liver and other organs, and functional reduction in nociceptor excitability in vivo. Transition to the R33 phase depends on meeting quantitative criteria for nociceptor delivery and reduction in pain signaling. The research addresses a substantial clinical gap: approximately 48 million surgical procedures occur annually in the United States, and six percent of patients who receive opioids for postsurgical pain continue using them six months later. Current systemic pain treatments carry higher adverse effect risk than focal approaches.

Performance occurs at Massachusetts General Hospital's Research Management Division in Charlestown, Massachusetts. The project period runs through July 31, 2028. This is a Project Grant, classified as assistance funding.