DataVXAdvanced SciencePaper
journal article·2026-06-26Open access

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

Yun Ji, Tao Li, Guoqiang Lei, Huichun Luo, Xiuqian Guo, Jiao Xiang, Tao Shi, Weitang Liu, Yuxin Zhang, Xiaoyu Liao, Shutao Zhao, Jiayun Wu, Wangao Zhang, Wenhui Liu, Chuanglong He, Shuo Chen, Tao Wu, Ke Ma

Advanced Science
Publisher pageOpen full text
Source abstract

Abstract

ABSTRACT 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.
Source: crossref · Quality: baseline

Research context

PolymersBiomaterials

OpenAlex topics: Pain Mechanisms and Treatments · Neuroscience and Neural Engineering · Neurological disorders and treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pain Medicine Xinhua Hospital Affiliated to Shanghai Jiao Tong University Shanghai China

Department of Orthopedics School of Medicine Xin Hua Hospital Affiliated to Shanghai Jiao Tong University Shanghai China

State Key Laboratory of Advanced Fiber Materials College of Biological Science and Medical Engineering Donghua University Shanghai China

Department of Anesthesiology Renji Hospital Affiliated to Shanghai Jiao Tong University Key Laboratory of Anesthesiology (Shanghai Jiao Tong University) Ministry of Education Shanghai China

Department of Pain The Second Affiliated Hospital of Anhui Medical University Hefei China

Department of Pain The Second Affiliated Hospital of Kunming Medical University Kunming China

Institute of Infectious Disease and Biosecurity Fudan University Shanghai China

Department of Oral Surgery Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University Shanghai China

Department of Rehabilitation Medicine The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Suzhou China

Institute for Developmental and Regenerative Cardiovascular Medicine MOE‐Shanghai Key Laboratory of Children's Environmental Health Xin Hua Hospital Affiliated to Shanghai Jiao Tong University Shanghai China

Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Pain Medicine First Affiliated Hospital of Anhui University of Chinese Medicine Hefei China

People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou China

School of Health Science and Engineering University of Shanghai for Science and Technology Shanghai China

Centre for Collaborative Research Shanghai University of Medicine and Health Sciences Shanghai China

Department of Pain Medicine Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China

Funding

National Natural Science Foundation of China

References (38)

Show source-provided references
1. Neuropathic Pain10.1038/nrdp.2017.2 ↗
2. Mechanisms of Neuropathic Pain10.1016/j.neuron.2006.09.021 ↗
3. The Analgesic Effects and Neural Oscillatory Mechanisms of Virtual Reality Scenes Based on Distraction and Mindfulness Strategies in human Volunteers10.1016/j.bja.2023.09.001 ↗
4. Pharmacotherapy for Neuropathic Pain in Adults: A Systematic Review and Meta‐Analysis10.1016/S1474-4422(14)70251-0 ↗
5. Pharmacotherapy of Neuropathic Pain10.1097/01.j.pain.0000460358.01998.15 ↗
6. The Benefits and Safety of a Virtual Reality Intervention in Patients Suffering from Acute and Chronic Pain: A Pilot Study10.1177/20552076241308703 ↗
7. Brain‐Machine Interfaces: From Basic Science to Neuroprostheses and Neurorehabilitation10.1152/physrev.00027.2016 ↗
8. Exploring Cognition with Brain–Machine Interfaces10.1146/annurev-psych-030221-030214 ↗
9. Discussion on the Composition and Implementation of Diagnosis and Treatment Strategies for Whole Field Pain Management Strategy
10. When Does Pain Matter? Acknowledging the Subjectivity of Clinical Significance10.1016/j.pain.2012.07.033 ↗
11. Neuropathic Pain: From Mechanisms to Treatment10.1152/physrev.00045.2019 ↗
12. Closed‐Loop Stimulation Using a Multiregion Brain‐Machine Interface Has Analgesic Effects in Rodents10.1126/scitranslmed.abm5868 ↗
13. Pain Control by Co‐Adaptive Learning in a Brain‐Machine Interface10.1016/j.cub.2020.07.066 ↗
14. A Prototype Closed‐Loop Brain–Machine Interface for the Study and Treatment of Pain10.1038/s41551-021-00736-7 ↗
15. Chronic Probing of Deep Brain Neuronal Activity Using Nanofibrous Smart Conducting Hydrogel‐Based Brain–Machine Interface Probes10.1002/smsc.202400463 ↗
16. Interfacing with the Brain: How Nanotechnology Can Contribute10.1021/acsnano.4c10525 ↗
17. Flexible Electrodes for Brain–Computer Interface System10.1002/adma.202211012 ↗
18. Electron Conductive and Transparent Hydrogels for Recording Brain Neural Signals and Neuromodulation10.1002/adma.202211159 ↗
19. Bioadhesive and Conductive Hydrogel‐Integrated Brain‐Machine Interfaces for Conformal and Immune‐Evasive Contact with Brain Tissue10.1016/j.matt.2022.01.012 ↗
20. Recent Progress of Hydrogels in Brain‐Machine Interface10.20517/ss.2024.34 ↗
21. An Injectable Rapid‐Adhesion and Anti‐Swelling Adhesive Hydrogel for Hemostasis and Wound Sealing10.1002/adfm.202207741 ↗
22. 10.1016/j.expneurol.2026.11564910.1016/j.expneurol.2026.115649 ↗
23. 10.1093/ijnp/pyaf01710.1093/ijnp/pyaf017 ↗
24. EEG Recordings as Biomarkers of Pain Perception: Where Do We Stand and Where to Go?10.1007/s40122-022-00372-2 ↗
25. Mechanically Robust, Negative‐Swelling, Mussel‐Inspired Tissue Adhesives10.1002/adhm.201200316 ↗
26. Recent Advances in Polysaccharide‐Based Hydrogels for Synthesis and Applications10.1002/agt2.21 ↗
27. Tannic Acid: A Versatile Polyphenol for Design of Biomedical Hydrogels10.1039/D2TB01056A ↗
28. Advances in Electrically Conductive Hydrogels: Performance and Applications10.1002/smtd.202401156 ↗
29. Conducting Hydrogel‐Based Neural Biointerfacing Technologies10.1002/adfm.202422869 ↗
30. Conducting Polymer Dough for Deformable Electronics10.1002/adma.201502947 ↗
31. Solid‐Diffusion Synthesis of Single‐Atom Catalysts Directly from Bulk Metal for Efficient CO2Reduction10.1016/j.joule.2018.11.008 ↗
32. Room‐Temperature‐Formed PEDOT:PSS Hydrogels Enable Injectable, Soft, and Healable Organic Bioelectronics10.1002/adma.201904752 ↗
33. Fatigue‐Resistant Conducting Polymer Hydrogels as Strain Sensor for Underwater Robotics10.1002/adfm.202305705 ↗
34. Solvent‐Free and Skin‐like Supramolecular Ion‐Conductive Elastomers with Versatile Processability for Multifunctional Ionic Tattoos and on‐Skin Bioelectronics10.1002/adma.202304157 ↗
35. A Reusable Hydrogel Biosensor Array with Electrically Responsive Hydrogel Interfaces for Noninvasive Locating of Perforating Arteries10.1126/sciadv.adw6166 ↗
36. Formulation and Characterization of Poloxamine‐Based Hydrogels as Tissue Sealants10.1016/j.actbio.2012.03.003 ↗
37. Electrode Materials for Brain–Machine Interface: A Review10.1002/inf2.12234 ↗
38. Activation of Parabrachial Nucleus ‐ Ventral Tegmental Area Pathway Underlies the Comorbid Depression in Chronic Neuropathic Pain in Mice10.1016/j.celrep.2021.109936 ↗