Cerebral Mechanism of Tuina on the Descending Pain Inhibitory System in Knee Osteoarthritis: Protocol for a Randomized Controlled Trial
Bibliographic record
Abstract
BACKGROUND: Knee osteoarthritis (KOA) is reputedly the most common musculoskeletal disease of the lower limbs and the main cause of pain and disability among older individuals. Pain is the most significant and widespread symptom of KOA. The descending pain inhibitory system has a cardinal role in normal pain consciousness, and its malfunction may be one of the pathophysiological mechanisms in KOA. Crucially, the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), as important components of the descending pain inhibitory system, directly modulate the activity of the spinal neurons involved in pain transmission. Tuina, a manual therapy, is effective and safe for reducing clinical symptoms of KOA; however, the mechanism that influences pain through the descending pain inhibitory system in KOA is unclear. OBJECTIVE: This study aims to investigate the modulatory implications of Tuina on the RVM and PAG, which have critical roles in the descending pain inhibitory system in patients with KOA. METHODS: This randomized controlled parallel trial will be conducted at the Tuina Clinic of the Third Affiliated Hospital of Henan University of Chinese Medicine (Zhengzhou, China). Patients with KOA will be randomly assigned (1:1) to 6 weeks of health education or Tuina. All patients in both groups will accept a resting-state functional magnetic resonance scan at the beginning and end of the experiment, and the resting-state functional connectivity and the voxel-based morphometry analysis will be performed to detect the RVM and PAG function and structure changes. The clinical outcome assessments will be (1) the pressure pain thresholds, (2) the Numerical Rating Scale, (3) the Hamilton Depression Scale (HAMD), and (4) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Considering that this trial is a study of resting-state functional magnetic resonance imaging technology, resting-state functional connectivity and voxel-based morphometry are the primary outcomes, and clinical outcome assessments are secondary outcomes. Adverse events will be documented and assessed throughout. All main analyses will be carried out on the basis of the intention-to-treat principle. The outcome evaluators and data statisticians will be masked to the treatment group assignment to reduce the risk of bias. RESULTS: This trial was approved by the ethics committee of the Third Affiliated Hospital of Henan University of Chinese Medicine. Enrollment began in December 2023, and the results of this trial are expected to be submitted for publication in May 2025. CONCLUSIONS: This trial will identify a possible relationship between function and structure changes of RVM and PAG and the improvement of clinical variables, elucidating the effect of Tuina on the descending pain inhibitory system of patients with KOA. This trial will provide much-needed knowledge for Tuina for patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070289; https://www.chictr.org.cn/showproj.html?proj=182570. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52820.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.015 | 0.016 |
| Meta-epidemiology (narrow) | 0.006 | 0.002 |
| Meta-epidemiology (broad) | 0.012 | 0.005 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.007 | 0.006 |
| Insufficient payload (model declined to judge) | 0.055 | 0.007 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".