Semi-Implantable Micro-Cooler for Dorsal Root Ganglion Enables Targeted, Sustained, and Cumulative Pain Relief

Pain remains a major clinical challenge, with current pharmacological treatments often limited by side effects, tolerance, and variable efficacy. The dorsal root ganglion (DRG) has emerged as a promising target for neuromodulation due to its pivotal role in pain signaling. In this study, we developed a miniaturized, semi-implantable cryo-neuromodulation device capable of delivering localized and reversible cooling to the lumbar DRG in awake, freely moving mice. Using a complete Freund's adjuvant (CFA)-induced inflammatory pain model, we demonstrated that DRG cooling at 29°C-but not 31.5°C-significantly reversed both mechanical and thermal hypersensitivity. The analgesic effect persisted for up to one hour post-cooling and exhibited cumulative improvement over repeated daily sessions, suggesting the induction of neuroplastic changes. Crucially, in a conditioned place preference test, CFA mice spent significantly more time in the chamber paired with DRG cooling, demonstrating that the pain relief is rewarding and motivationally salient. These findings establish DRG-targeted cryo-neuromodulation as a potent, non-pharmacological strategy for pain management, with implications for the development of precision neuromodulation therapies for pain.