A Nature paper described a gene therapy approach that targets cortical pain circuits to reproduce opioid-like analgesia without addiction in mouse models. Researchers used circuit-specific manipulations and an AI-driven behavioral platform to show that the treatment reversed neuropathic neural dynamics that encode affective pain, reducing pain-motivated behaviors while avoiding opioid-associated reward and addiction pathways. The study—led by investigators at the University of Pennsylvania and published in Nature—provides preclinical proof-of-concept for CNS-targeted gene therapies aimed at disentangling analgesia from addiction. Authors emphasized this as a potential blueprint for non-addictive, circuit-specific pain medicine, noting further work is required before human translation.