GPR37 and GPR37L1 Agonists for Non-Addictive Pain Resolution in Inflammatory and Neuropathic Pain

Unmet Need

Chronic pain remains a widespread clinical issue, with existing treatments primarily focused on symptom suppression rather than addressing the biological mechanisms driving pain persistence. Opioids and NSAIDs provide temporary relief but fail to promote long-term recovery. There is a need for a non-addictive therapy that enhances pain resolution by targeting neuroimmune pathways.

Technology

Duke inventors have developed a pain treatment strategy targeting GPR37 and GPR37L1 receptors, which play key roles in neuroimmune signaling and pain resolution. This is intended to be a novel, biologically-driven approach for treating inflammatory, neuropathic, and cancer-related pain by modulating immune and neuronal interactions. Specifically, GPR37 activation by agonists such as neuroprotectin D1 (NPD1) and prosaptide TX14 enhances macrophage-driven inflammation resolution, while GPR37L1 activation via maresin 1 (MaR1) and small-molecule ligands restores perineural homeostasis by regulating glial cell activity and potassium channel function. This has been demonstrated in preclinical models, where activation of these receptors led to reduced hyperalgesia, inflammation, and sustained pain resolution.

Other Applications

This technology could also be applied to other neuroimmune and inflammatory diseases, including sepsis, neurodegenerative disorders, and injury-induced neuropathies, where modulating immune-glial interactions may provide therapeutic benefits.

Advantages

• Dual-action approach targeting macrophages (GPR37) and glial cells (GPR37L1) for comprehensive pain relief
• Potential for disease modification, promoting pain resolution rather than temporary symptom relief
• Broad therapeutic potential, with applications extending to neuroimmune disorders beyond pain
• Demonstrated efficacy in preclinical models, showing reductions in hyperalgesia and neuroinflammation