Neurofeedback Training for Managing Neuropathic Pain–Like Features in Chronic Musculoskeletal Pain: Protocol for an Open-Label Pilot Feasibility Clinical Trial

Background Neuropathic pain (NP) is characterized as pain arising from lesions of the somatosensory nervous system. However, NP-like features have been found in several chronic secondary musculoskeletal (MSK) pain conditions in the absence of detectable lesion or damage to the somatosensory pathways. Emerging evidence has demonstrated associations between NP-like symptoms and altered neural activity within brain regions implicated in sensory perception and affective-emotional processing of pain with consistent findings of abnormal activity in the right insula (RIns) cortex and dorsal anterior cingulate cortex (dACC). Electroencephalography neurofeedback (EEG-NF) is a brain-computer interface biofeedback technique that allows individuals to self-regulate the real-time cortical brain activities of the regions of interest. Objective The primary objective of this study is to investigate the feasibility and safety of a novel EEG-NF intervention designed to simultaneously downtrain activity in the RIns and dACC in individuals with a chronic secondary MSK pain condition exhibiting NP-like features. In addition, this study will conduct secondary exploratory analyses to investigate EEG-derived neuronal changes and their associations with clinical and experimental pain outcomes following the EEG-NF training. Methods We will design a single-arm, open-label, pilot-feasibility trial. We will recruit adults aged 35-75 years with a score of ≥19 using the PainDETECT questionnaire and an average pain score of ≥4 on the 11-point Numeric Pain Rating Scale over the last 3 months, with a minimum pain duration of 3 months, to receive active EEG-NF training. Participants will receive auditory feedback as a reward for achieving a predetermined activity threshold of the RIns and dACC. Primary outcomes will evaluate feasibility, acceptability, and safety using both self-reported questionnaires and monitoring data. Collected data will be summarized descriptively, with mean (SD) reported where appropriate. Secondary outcomes will include EEG parameters, self-reported measures, heart rate variability, and quantitative sensory testing. An exploratory within-group pre-post statistical comparison will be conducted for all secondary outcome measures, and correlation analysis will be performed to explore relationships between EEG measures, self-reported outcomes, heart rate variability, and quantitative sensory testing measures. Results This study has received approval from the Health and Disability Ethics Committee and is registered with the Australian New Zealand Clinical Trials Registry. Participant recruitment began in April 2025 and is ongoing. As of October 2025, data collection has been completed, with a total of 5 participants enrolled, all of whom have completed the study to date. We expect to complete the study in March 2026. This study will generate data on feasibility, safety, acceptability, and preliminary data to inform a fully powered effectiveness clinical trial. Conclusions The results and data generated will inform the design and sample size calculation for a fully powered randomized controlled trial aimed at evaluating the effectiveness of EEG-NF in targeting NP-like features in individuals with chronic MSK pain. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12625000706471; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=389568&isReview=true International Registered Report Identifier (IRRID) DERR1-10.2196/78806