Closed‐Loop Decoding and Intervention of Pain: A Novel BMI Strategy Integrating θ ‐Band Detection and Mechano‐Electro‐Biological Coupled Hydrogels

Neuropathic pain (NP) lacks objective biomarkers and effective therapies. We developed a closed‐loop brain‐machine interface (BMI) using a novel hydrogel electrode for integrated NP management. Clinically, we identified enhanced prefrontal θ‐band (4–8 Hz) activity as a specific NP biomarker. To achieve stable long‐term recording, we engineered a PFAPT hydrogel with superior biocompatibility, anti‐swelling, and low impedance. In rats, it enabled stable electrocorticography (ECoG) acquisition for 28 d, outperforming screw electrodes, and validated θ‐band alterations in NP. Incorporated into a closed‐loop BMI, the hydrogel delivered θ‐triggered cortical stimulation, which increased pain thresholds and alleviated anxiety‐ and depression‐like behaviors in NP rats. Spatial transcriptomics revealed that stimulation bidirectionally regulated inflammation, central sensitization, and affective pathways. This work presents a hydrogel‐based closed‐loop BMI as a precise diagnostic and therapeutic platform for NP.