This clinical trial will be an open-label RCT designed to compare naprapathy plus physical therapy and physical therapy in treating BPI. This protocol has been registered on the Chinese Clinical Trial Registry (2100043515) and will be performed in accordance with the Declaration of Helsinki. The study flowchart is shown in Figure 1.

Recruitment will be carried out at Yue Yang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. A total of 116 participants with BPI will be enrolled. Recruitment will be carried out through social platforms and outpatient departments. The study team will educate physicians about the study, focusing on those who do the surgery for patients with BPI. If the patients meet the inclusion criteria and are willing to participate in the trial, they will be asked to provide written informed consent. Then, they will be randomized into the naprapathy plus physical therapy group (group A) or the physical therapy group (group B) by LZ and BP.

The study protocol was approved by the ethics review committee of Yue Yang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine (2021-012). Any changes including eligibility criteria, outcomes, and so forth should be reported to the Ethics Review Committee. The ethics committee of Yueyang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine will audit the whole procedure during the clinical trial conducted independently from investigators and the funder. The participants signed the informed consent and agreed to the primary and secondary analyses of their data without additional consent. All the study data are deidentified. This trial has also been registered in the Chinese Clinical Trial Registry (2100043515). The results of the preliminary study will be published in a professional journal.

Patients and the public are involved in the design of the study. They reviewed the study proposal and attended the design meetings. Patients and the public will be included in all research communications.

The inclusion criteria are as follows: (1) aged 18 to 70 years; (2) BPI diagnosed by history, physical examination, electromyography, or surgical exploration more than 2 weeks after nerve surgery; (3) agreement to provide written informed consent.

The exclusion criteria are as follows: (1) concurrent damage to major organs, such as the heart, kidneys, liver, and so forth; (2) severe cardiovascular or cerebrovascular disease, liver or kidney dysfunction, metabolic disease, or mental illness; (3) chronic illness, physical discomfort, frailty, severe neurosis, or pregnancy; (4) primary brachial plexus pain or brachial plexus neuritis; (5) brachial plexus pain due to cervical spondylosis, tennis elbow, carpal tunnel syndrome, frozen shoulder, biceps tenosynovitis, thoracic outlet syndrome, or other secondary causes.

The participants will be withdrawn if they have the following: (1) missing or incomplete patient treatment records, which would affect the final data analysis; (2) treatment with other methods at the same time; (3) any severe adverse reactions or other emergent symptoms during the treatment (such as aggravation of disease or severe depression and the need for special treatment).

In this clinical trial, a total of 116 participants with BPI will be randomly assigned to either group A (naprapathy plus physical therapy) or group B (physical therapy) at a 1:1 ratio. The random sequence will be generated using SAS software (version 9.3; SAS Institute, Inc). The coauthors randomizing the participants are not linked to any statistical work.

The treatment plan of this trial is based on naprapathy in clinical rehabilitation for the treatment of BPI. Participants in group A will receive naprapathy in addition to physical therapy, while participants in group B will receive physical therapy only. Treatment in both groups will last 4 weeks. The interventions in this trial involve rigorous naprapathy and physical therapy schedules. To ensure the compliance of naprapathy practitioners and physical therapists with their schedules, they will be asked to undergo pretrial training, after which they will be required to pass an entrance examination to participate in this trial. All included naprapathy practitioners and physical therapists will have at least 5 years of practical experience in clinical rehabilitation.

All participants will receive physical therapy, such as neuromyoelectric stimulation by a transcutaneous electrical nerve stimulator (TENS 21, Homer Ion), medium-frequency electrotherapy by a medium-frequency electrical stimulator (ES-521, Ito), and continuous passive motion by an upper limb continuous passive motion joint rehabilitation device (2029, DJO), once each day for 5 continuous days in a week. Each therapy session will last for 40 minutes and will be performed 5 times a week (from Monday to Friday) for a total of 20 sessions in 4 weeks.

For patients with total BPI, the patient will take a sitting position. The naprapathy practitioner will stand on the affected side and first apply Yizhichan (one-finger Zen) (Figure 2) pushing manipulation and press-kneading manipulation at Fengchi (GB 20, affected side), cervical Jiaji points (EX-B2, affected side), Jianjing (GB 21, affected side), Jianyu (LI 15, affected side), Quchi (LI 11, affected side), Waiguan (SJ 5, affected side), and Hegu (LI 4, affected side). Then, the practitioner will apply rolling manipulation (Figure 3) from the affected shoulder to the upper limb and grasping manipulation (Figure 4) on the neck, shoulder, and upper limb. Finally, the hand-shoulder shaking (Figure 5) method will be applied to help soothe the joints. Within the allowable safety range of the affected limbs, the joints of the upper limbs will be passively moved.

For patients with upper trunk BPI, the naprapathy practitioner will apply Yizhichan pushing and press-kneading manipulations at Fengchi (GB 20, affected side), Yunmen (LU 2, affected side), Quchi (LI 11, affected side), Shousanli (LI 10, affected side), Hegu (LI 4, affected side), Yangxi (LI 5, affected side), Sanjian (LI 3, affected side), Yuji (LU 10, affected side), and Laogong (PC 8, affected side). The other methods will be the same as above.

For patients with lower trunk BPI, the naprapathy practitioner will apply Yizhichan pushing and press-kneading manipulations at Tianzong (SI 11, affected side), Jianzhen (SI 9, affected side), Waiguan (SJ 5, affected side), Yangchi (SJ 4, affected side), Jianwaishu (SI 14, affected side), Xiaohai (SI 8, affected side), Yanglao (SI 6, affected side), Yanggu (SI 5, affected side), and Houxi (SI 3, affected side). The other methods will be the same as above.

The duration of each naprapathy session will be 20 minutes and will be performed 5 times a week (every Monday to Friday) for a total of 20 sessions in 4 weeks. If there are any adverse events, the treatment will be suspended, and the investigator will decide whether to terminate the treatment.

All the acupoints used in this study are shown in Figures 6 and 7.

Outcomes will be evaluated at 2 time points: baseline and at the completion of treatment. An overview of the outcomes measured at the different time points is shown in Table 1.

According to clinical experience and the literature, naprapathy may cause several kinds of adverse events, such as subcutaneous hematoma, edema, skin bruising, local pain, and fainting. Among these adverse events, subcutaneous hematoma and edema are the most common. Naprapathy-related safety and adverse events will be carefully recorded using case report forms. Adverse events should be reported to the ethics committee of Yueyang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine. The Ethics Committee has the right to stop the intervention of the participant.

All our measures will be free of charge to ensure complete participation in the follow-up evaluation. Case report forms will be completed in paper form and stored by the Shanghai University of Traditional Chinese Medicine. Data will be collected according to Table 1 by investigators, and personal information about the enrolled participants will be kept in Yueyang Hospital in order to protect confidentiality in the whole trial. The ethics committee of Yueyang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine will audit the trial every 12 months and will establish a data monitoring committee, which is independent from the funder and has no competing interests. The data will be stored in the clinical trial public management platform and ready for public inquiry after the trial. A quality control group independent from the research team will be set up to control the quality of this study.

Our previous study indicated that 58.5% of patients with BPI showed improvements in upper extremity function and muscle strength [23]. In this clinical trial, the rate of upper extremity function recovery is expected to be 75% in the naprapathy group and 55% in the physical therapy group. With α=.05 and β=.01, a total of 52 participants will be needed, as calculated using SPSS software (version 21.0; IBM Corp). According to the previous study, a 10% withdrawal rate will also be considered; therefore, each group will include at least 58 participants.

All data will be analyzed by researchers using SPSS (version 21.0) software. Data will be expressed as the mean (SD) or median (IQR). First, the data will be tested for normality and homogeneity of variance; if the data meet the requirements for a normal distribution, the homogeneity of variance will be analyzed by the F test. In the case of heterogeneity, the corrected t test will be used. If the requirements for normality and homogeneity of variance are not satisfied, the rank-sum test will be used. If the sphericity test yields a P value less than .05, indicating that the assumption of sphericity is violated, we will perform multivariate analysis. A statistically significant result (P<.05) for the time factor will indicate that the measurements show a trend of changing over time. A statistically significant (P<.05) interaction between time and group will indicate that in addition to the effect of time, there are differences between the groups. If a P value is less than .05, the difference will be considered statistically significant, indicating a difference in the results between the two groups. If a P value is greater than .05, then the difference will not be considered statistically significant, indicating no difference in the results between the two groups. Cohen d (sample size) will also be used to compare differences between groups, and the generalized linear model will be applied to explore differences in outcomes between groups.

For safety analysis, adverse event data are generally expressed as the number of events and the percentage of cases involved in the adverse event.