
==== Front
BMJ Open
BMJ Open
bmjopen
bmjopen
BMJ Open
2044-6055
BMJ Publishing Group BMA House, Tavistock Square, London, WC1H 9JR

39260860
10.1136/bmjopen-2024-083986
bmjopen-2024-083986
Protocol
Rehabilitation Medicine
1727
1506
Investigating combined acupuncture and transcranial direct current stimulation in patients with poststroke shoulder pain from China: protocol for a randomised controlled trial
http://orcid.org/0009-0005-9224-5906
Chen Jincheng 1230494336046@qq.com

Lin Zhigang 10drlzg2014@126.com

Chen Shuijin 1fujiantuina@126.com

He Jian 4591003659@qq.com

http://orcid.org/0000-0001-7212-3147
Liu Weilin 5liuweilin12@fjtcm.edu.cn

Liu Zhizhen 6lzz@ftcm.edu.cn

http://orcid.org/0000-0003-3917-983X
He Youze 31257453772@qq.com

Rao Ting 3719888386@qq.com

Yang Yihan 3995420005@qq.com

Lin Rong 3254524306@qq.com

Cheng Jing 1592826834@qq.com

Jiang Yijing 1290658478@qq.com

Yang Shanli 149688400@qq.com

1 Rehabilitation Hospital affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China
2 Fujian Key Laboratory of Rehabilitation Technology, Fuzhou, China
3 College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China
4 Zhangzhou Health Vocational College, Zhangzhou, Fujian, China
5 The Academy of Rehabilitation Industry, Fujian University of Traditional Chinese Medicine, Fuzhou, China
6 Science and Technology Branch, Fujian University of Traditional Chinese Medicine, Fuzhou, China
DrShanliYang; 49688400@qq.com
None declared.

JC and Z-GL contributed equally.

2024
10 9 2024
14 9 e08398605 1 2024
09 8 2024
Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Abstract

Introduction

Poststroke shoulder pain is a common complication that severely affects the recovery of upper limb motor function. Acupuncture has positive analgesic effects in treating poststroke shoulder pain, and studies have demonstrated the efficacy of transcranial direct current stimulation (tDCS) in treating patients with this pain. However, whether acupuncture combined with tDCS has a superior rehabilitation effect on poststroke shoulder pain is currently unknown. We aimed to observe the effect of the combined intervention on poststroke shoulder pain and explore its possible central analgesic mechanism.

Methods and analysis

This study describes a randomised controlled trial using assessor blinding. A total of 135 poststroke patients with shoulder pain will be randomly assigned in a 1:1:1 ratio to the tDCS group, acupuncture group and combined group (acupuncture plus tDCS). All three groups will undergo conventional rehabilitation treatment. Participants in the tDCS group will receive tDCS stimulation on the M1 area for 20 min, while the acupuncture group will receive 20 min of acupuncture. The combined treatment group will receive both. All treatments will be performed five times per week for 4 weeks. The primary outcome indicator in this study is the Visual Analogue Scale pain score. Secondary outcome indicators include shoulder mobility, Shoulder Pain and Disability Index, Fugl–Meyer Motor Function Scale, Modified Barthel Index Scale, Self-Rating Anxiety and Depression Scale and functional MRI. All scale results will be assessed at baseline and at 2 weeks and 4 weeks, and during follow-up at 1 month, 3 months and 6 months postdischarge. A repeated analysis of variance will be conducted to observe the group×time interaction effects of the combined intervention. Moreover, functional MRI will be applied to explore the central analgesic mechanism.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (2023KY-039–001). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences.

Trial registration number

ChiCTR2300078270.

stroke
shoulder
randomised controlled trial
acupuncture
http://dx.doi.org/10.13039/501100012166 National Key Research and Development Program of China 2022YFC2009700 http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China 82074513 http://dx.doi.org/10.13039/501100003392 Natural Science Foundation of Fujian Province 2020J01760 Fujian province University Industry University Cooperation Project 2021Y4017
==== Body
pmcSTRENGTHS AND LIMITATIONS OF THIS STUDY

The intervention protocol used in this study will be evidence-based and rigorously developed based on evidence, recommendations, theories and practical criteria of systematic evaluation.

Sensitive, systematic and comprehensively valid evaluation results were selected, including subjective pain, psychological scales, objective functional assessment scales and functional MRI (fMRI) tests. Subjectivity and objectivity were combined to reduce the bias of confounding factors.

fMRI was used to reveal the possible central analgesic mechanism of transcranial direct current stimulation combined with acupuncture for treating poststroke shoulder pain, paving the way for subsequent in-depth mechanistic studies.

The source of case data was a single healthcare provider, and the lack of multicentre healthcare provider data affected the level of evidence for the study results.

Due to the visibility of the intervention, the design could not be blinded to participants and study researchers in the current study protocol.

Introduction

Stroke is the most common cerebrovascular disease in clinical practice, and survivors often suffer from varying degrees of functional impairment. Poststroke shoulder pain, occurring on the hemiplegic side of the patient, is a common complication after stroke. Epidemiological studies have reported that approximately 30%–65% of patients with stroke suffer from shoulder pain, and the main clinical presentations are shoulder pain and limited shoulder joint movement.1 2 Poststroke shoulder pain occurs in the chronic stage after stroke, usually 2–3 months thereafter. This pain can last for months or even years, is an important complaint of patients during medical consultations, and is the focus of attention of clinicians.3

Poststroke shoulder pain affects the recovery of upper limb motor function, thereby reducing shoulder mobility. The development of poststroke shoulder pain may affect recovery from other dysfunctions after stroke, leading to a lower level of daily living ability and limiting the return of patients to society and family life.4 Persistent pain not only affects the recovery of limb function but may also cause varying degrees of depression or anxiety, which will reduce quality of life, affect motivation to continue treatment, make withdrawal from the rehabilitation training programme easier, prolong rehabilitation treatment time, affect overall recovery and increase the burden on the patient and the community.5

To date, the exact pathogenesis of poststroke shoulder pain remains controversial due to the complex and multifactorial aetiology thereof, involving soft muscle tissue, motor control, neurological (peripheral and central nervous system) and psychological factors.6 Patients with poststroke shoulder pain reduce the activity of the affected limb due to muscle strength, tension, pain, spasm, dislocation and other reasons. This reduces stimulation of the brain by external factors, which is not conducive to the functional reorganisation of the brain, reducing upper limb function.7

Acupuncture, as a traditional therapy of Chinese medicine, has become an increasingly popular technique in recent years. It is widely used in treating various kinds of pain and is recognised as having efficacy in pain relief. Furthermore, clinical and basic research regarding acupuncture analgesia is a research hotspot.810 Additionally, acupuncture has also been applied in treating poststroke shoulder pain with clinical efficacy,11 12 to improve pain, upper limb motor function and daily living ability in these patients.1315 A narrative review of clinical guideline recommendations for acupuncture as a treatment for poststroke dysfunction noted that the evidence for acupuncture for poststroke shoulder pain is increasing, with most evidence suggesting a positive analgesic effect.16

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation based on the principle of applying low-intensity electrical currents directly to the scalp, providing a safe stimulation technique to directly modulate neuronal activity and induce neuroplasticity changes. This is mainly manifested in the human motor cortex, such as the primary motor cortex (M1).17 18 tDCS can reduce pain in patients by altering the excitability of the cerebral cortex.19 Studies have demonstrated the safety and efficacy of tDCS in treating patients with post-stroke shoulder pain,20 and tDCS has been shown to reduce the magnitude and duration of pain and improve the quality of life of patients.2123 tDCS is, therefore, a safe intervention to improve upper extremity pain and spasticity in stroke patients.24 25

Although a variety of rehabilitation therapies have been proposed for the treatment of poststroke shoulder pain, their therapeutic efficacy is inconsistent, and a single treatment may be insufficient. A combination of effective multidisciplinary interventions is required to further improve rehabilitation outcomes.26

Studies using functional MRI (fMRI) have shown that acupuncture can promote the recovery of cortical function by improving cognitive networks, which in turn relieves pain and improves limb motor function. Neuroplasticity and functional remodelling are potential rehabilitation mechanisms for acupuncture to improve shoulder pain after stroke, which has been confirmed by fMRI brain assessment techniques. Furthermore, repeated stimulation during acupuncture promotes the formation of functional neural pathways and activates the formation of new synapses. In other words, functional improvement and strengthening depend on cortical excitation and functional remodelling.27 28

From the perspective of neurorehabilitation, the combination of brain stimulation techniques and acupuncture may achieve a synergistic effect on functional rehabilitation, and the mutual combination may amplify neuroplasticity and functional remodelling. We hypothesised a synergistic effect of acupuncture combined with tDCS for the treatment of poststroke shoulder pain. However, it is unclear whether this combination will effectively improve this pain.

We, therefore, aimed to investigate whether the integration of tDCS and acupuncture has a synergistic effect on the improvement of shoulder pain after stroke. The randomised controlled trial (RCT) was designed with three groups, including a tDCS group, acupuncture group and tDCS combined with acupuncture group. It was hypothesised that these groups would show different improvements in primary and secondary outcomes. Our results may provide a further understanding of existing rehabilitation techniques and assist in the design of a more effective rehabilitation programme for poststroke shoulder pain.

Methods and analysis

Study design

This study will be a single-blind RCT consisting of a 4-week intervention and a 6-month follow-up. In total, 135 patients with poststroke shoulder pain were randomly divided into tDCS (control group A), acupuncture (control group B) and tDCS–acupuncture (intervention group C) groups in the ratio of 1:1:1. A brief flowchart of the study is shown in figure 1 and the schedule of activities is shown in table 1. The protocol was reported in accordance with the standard protocol items of randomised trials.29 The study protocol was approved by the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (No. 2023KY-039–001) and registered in the China Clinical Trial Registry.

Table 1 Schedule of enrolment, intervention and assessments

Timepoint	Study period	
Screening	Baseline	Treatment	Follow-up	
1 month	0	2 weeks	4 weeks	1 month	3 months	6 months	
Enrolment								
 Eligibility screen	✓							
 Informed consent	✓							
 Demographic information	✓							
 Descriptive information		✓						
 Randomisation		✓						
 Allocation		✓						
Interventions								
 tDCS group						
 Acupuncture group						
 tDCS–acupuncture group						
Efficacy assessments								
 VAS		✓	✓	✓	✓	✓	✓	
 SROM		✓	✓	✓	✓	✓	✓	
 SPADI		✓	✓	✓	✓	✓	✓	
 FMA		✓	✓	✓	✓	✓	✓	
 MBI		✓	✓	✓	✓	✓	✓	
 SAS		✓	✓	✓	✓	✓	✓	
 SDS		✓	✓	✓	✓	✓	✓	
 Brain structure and function		✓		✓			✓	
Safety assessments								
 Adverse event occurrence rate				✓			✓	
 Summary the study							✓	
✓ Means things will be done.

FMAFugl–Meyer AssessmentMBIModified Barthel IndexSASSelf-rating anxiety scaleSDSSelf-rating depression scaleSPADIShoulder Pain and Disability IndexSROMshoulder range of motiontDCStranscranial direct current stimulationVASVisual Analogue Scale

Figure 1 Study flow diagram. fMRI, functional MRI; tDCS, transcranial direct current stimulation.

Sample size calculation

The sample size was calculated by specifying an effect size based on minimal clinically important differences.30 Based on a previous two-way analysis of variance (ANOVA) F-test with a power of 0.80, an effect size of 0.25 and an alpha level of 0.05, it was estimated that 108 participants were needed for this study. Considering a dropout rate of approximately 20%, the final sample size will be 45 participants per group, for a total of 135 subjects.

Participants

Inclusion and exclusion criteria.

Inclusion criteria

(1) Clinical diagnosis of cerebral haemorrhage or cerebral infarction by CT/MRI; (2) age 18–85 years; (3) poststroke shoulder pain of ≥3 points in intensity (VAS ≥3/10) within the past 7 days; (4) >14 days after stroke; (5) mental health, the ability to answer questions, good communication skills and a Mini-Mental State Examination score ≥24.

Exclusion criteria

(1) Patients with craniocerebral trauma, thalamic disease or peripheral neuropathy; (2) there is a history of cervical spondylosis, shoulder periarthritis, shoulder fracture or trauma, osteoporosis, myocardial infarction, etc, which may cause shoulder pain; (3) patients with cerebral oedema or coma after stroke; (4) patients with serious infection or heart, liver or kidney disease; (5) those participating in other clinical trials that may affect the results of this study; (6) patients with severe cognitive deficits and aphasia.

Setting and recruitment

This study will be conducted at the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine. In this trial, participant recruitment will include advertising posters in the hospital (online WeChat and offline printed posters) and referrals from therapists or neurorehabilitation physicians. Details of the study will be communicated to potential participants. Patients will be invited to participate in this trial after voluntarily signing an informed consent form. Recruitment will begin from 1 December 2023 to 31 December 2026. All patients who meet the inclusion criteria and agree to participate will be asked to provide their written informed consent.

Randomisation, allocation concealment and blinding

Randomisation and allocation concealment will be provided by statistical analysts who are independent of the study team and are internationally accredited. Information (eg, demographic, clinical and outcome) on each participant who has signed the informed consent form and completed the preassessment will be uploaded to the online data management system. Participants will then be automatically randomly assigned to three groups in a 1:1:1 ratio according to the system’s built-in randomisation procedure. The acupuncturists at each centre would have been working at the hospital for at least 10 years, and acupuncturists and tDCS operators would receive uniform and standardised training.

Due to the visibility of the needling and tDCS interventions, blinding of study investigators and participants is not possible. Therefore, to avoid potential detection bias, blinding will only apply to the outcome assessor and statistician who will perform the final statistical analyses in this trial RCT. We will engage independent assessors who are not involved in the delivery of the intervention to ensure their impartiality. These assessors will be trained on the study protocol and blinded to the intervention status of the participants. The assessors will be responsible for data collection and analysis and will not be involved in the subject recruitment process. In the event that an assessor accidentally discovers the intervention group of a participant, we will immediately replace that assessor with an alternative blinded assessor. The success of the assessor blinding will be determined at the completion of the follow-up assessment for each participant by responding to the questions ‘Did you know which intervention group the participant was assigned to before the follow-up assessment was completed?’ and, ‘If “yes”, how did you find out?’

Intervention

The three groups will receive the same routine rehabilitation programme, including physiotherapy, occupational therapy and speech therapy. Rehabilitation interventions in all three groups will be for 5 days per week for 4 weeks (table 2).

Table 2 Overview of intervention

Group	Description	n	
tDCS group	Routine rehabilitation programme and tDCS anodal stimulation of the patient’s M1 area	45	
Acupuncture group	Routine rehabilitation programme and acupuncture	45	
tDCS–acupuncture group	Routine rehabilitation programme, tDCS and acupuncture	45	
tDCStranscranial direct current stimulation

tDCS group

The IS300 tDCS instrument (Sichuan Intelligent Electronics Industry, Chengdu, Sichuan, China) was used. The body surface was projected as the left and right hemispheric central areas, and the stimulation area was dominated by the side of stroke injury, such as the right side of the right hemisphere stroke stimulation of the right hemisphere central area, and the left hemisphere stroke stimulation of the left hemisphere central area. The cathode electrode sheet was placed in the contralateral supraorbital area of the patient; the stimulation current was 2 mA. The time of each stimulation was 20 min, five times per week and the treatment course was 4 weeks. The operation was performed by a physician qualified in neurophysiological training.

In the tDCS group, participants underwent treatment using the IS300 tDCS and a regular rehabilitation programme. Before performing the stimulation, the skin at the stimulated site was checked for wounds to avoid irritation of the damaged skin. In this study protocol, the tDCS instrument was used to stimulate the primary motor cortex, area M1 (C3 and C4), with the body surface projected as the central area of the left and right hemispheres.30 The stimulated area was mainly the side injured by stroke. For example, the central region of the right brain is stimulated in right stroke and the central region of the left brain is stimulated in left stroke. The cathode electrode was placed in the contralateral supraorbital region of the patient. The stimulation parameters were set to 2 mA dual head current with a relative current density of 0.057 mA/cm2 for 20 min, well within current safety limits.

Acupuncture group

Acupuncture points were selected for the treatment of shoulder pain from the ninth edition of the ‘Zhen Jiu Jia Yi Jing (Systematic Classic of Acupuncture and Moxibustion)’. The points were taken from the local shoulder joints, including shoulder Qian, Zhen, A Shi, Yanglingquan and Zhongping (one below Zusanli). At the same time, according to the pain location of the meridian differentiation of points, for Taiyin meridian syndrome, we added chi ze; Yin Lingquan; Yangming, Shaoyang classics, hand Sanli; Waiguan Sun classics, Houxi, Dashu and Kunlun; pain in Yangming, the sun plus mouth through Chengshan. Acupuncture techniques were used to supplement deficiency and reduce deficiency. Huatuo disposable acupuncture needles, 0.30 mm × 40 mm, were used for the acupuncture.

tDCS–acupuncture group

In the tDCS–acupuncture group, participants will receive a 20 min tDCS intervention, a 20 min acupuncture treatment and a conventional rehabilitation programme. tDCS and acupuncture interventions will be performed with stimulation modalities, sites, parameters and details as previously described.

Baseline characteristics of the participants

The demographics (eg, sex, age, marital status, accommodation address and telephone number) and clinical characteristics (eg, aetiology, clinical diagnosis, stroke type, stroke location and time since stroke onset) of the participants will be collected at baseline (T1).

Outcome measures

All outcome measures will be assessed by a research assistant who is a professional rehabilitation assessor and blinded to the RCT at baseline (T1), 2 weeks (T2) and 4 weeks (T3) during the intervention period and at 1 month (T4), 3 months (T5) and 6 months (T6) during the follow-up period (table 3). All outcome measures will be uploaded to the online data management system of the third-party data management organisation and will be kept in a secure and lock-protected location.

Table 3 Outcome measures and tools

	Outcome measures	Tool or methods	
Primary	Shoulder pain	Visual Analogue Scale	
Secondary	Shoulder range of motion	Universal protractor	
	Motor function	Fugl–Meyer Upper Limb Functional Assessment Scale	
	Shoulder pain and dysfunction	Shoulder Pain and Disability Index	
	Brain structure and function	fMRI system	
	Depression	Depression Self-assessment Scale	
	Anxiety level	Self-rating Anxiety Scale	
	Daily living ability	Modified Barthel Index	
Primary outcome measures.

Efficacy of intervention for shoulder joint dysfunction.

fMRIfunctional MRI

Shoulder pain

The VAS is used to assess pain in patients with poststroke shoulder pain. The VAS has been widely used in clinical pain assessment and has high reliability and validity. The minimum score is 0 and the maximum score is 10, and the scale consists of a 100 cm straight line. The VAS is simple, fast, accurate and easy to perform and determines the degree of pain relief. The scale is 10 cm long, labelled with 10 increments of 1 cm, with ‘0’ and ‘10’ at each end, with 0 indicating no pain, 10 indicating the most intolerable pain and the middle portion indicating different levels of pain. The patient is asked to mark the level of pain on the horizontal line according to subjective sensations.

Secondary outcome measures

Shoulder joint motion

Shoulder joint mobility was measured before and after treatment in all patients. This was performed in sitting or standing positions, with the long axis of the humerus as the mobile arm and shoulder flexion (with the acromion as the axis and the median line on the side of the body as the fixed arm) and abduction (with the acromion as the axis and the median line on the side of the body as the fixed arm) measured by a specialised practitioner using a general-purpose protractor.

Shoulder Pain and Disability Index

The Shoulder Pain and Disability Index is a method of assessing the degree of shoulder pain and dysfunction, including pain, activity function and other issues. The index is used to assess the severity of pain and the degree of difficulty in daily life. The total score is based on the total points of the pain and disability scale divided by the number of countable points out of a maximum of 100 points. The higher the score, the higher the degree of pain and dysfunction of the shoulder joint.

Motor function

The motor function of stroke patients was assessed using the Fugl–Meyer Assessment scale. The Fugl–Meyer Upper Limb Functional Assessment Scale is the most widely recognised and used assessment method in the field of hemiplegia in stroke and reflects the level of recovery of upper limb motor function after hemiplegia. The scale is comprehensive in its assessment, is highly sensitive and is often widely used in the evaluation of limb function in stroke patients, with a total score of 66. The score is positively correlated with the motor function of the upper limbs. The higher the score, the better the patient’s functional recovery.

Daily living ability

The Modified Barthel index (MBI) is a classic tool to assess a patient’s ability to perform activities of daily living and is widely used in clinical research. The index consists of 10 scores of daily living ability: eating, dressing, bathing, toileting, transferring to and from a chair, self-care in the toilet, non-self-care in the toilet, walking and walking up and down stairs. Each ability is scored with one point, with higher scores indicating better physical function. A score of 10 is given for complete self-care and 0 for complete lack of self-care. MBI has the advantages of being efficient, sensitive and reliable.

Depression level

The Self-rating Depression Scale (SDS) is a scale that provides an intuitive picture of the subjective feelings of depressed patients and how they change during treatment. The scale contains 20 items reflecting subjective feelings of depression, and each item is divided into four levels of scoring according to the frequency of symptoms. The normal upper limit of the SDS total score is 41, and the standard score is the integer part obtained by multiplying the total score by 1.25. The higher the score, the more serious the state of depression.

Anxiety level

The Self-rating Anxiety Scale is a self-rating scale used to assess an individual’s level of anxiety. The scale covers different aspects of anxiety, including subjective feelings, physical reactions and behavioural expressions. Each option is assigned a different score, which is calculated to give a total score, ranging from 20 to 80, with higher scores indicating more severe levels of anxiety.

Brain structure and function

3.0T functional MRI will be used to collect T1 structural images and resting state functional images of patients to evaluate and analyse the structural and functional plasticity of the brain. Functional nuclear magnetic resonance (NMR) data image acquisition was performed using a 3.0T Simens Prisma MRI scanner (Simens Prisma, Germany) with an eight-channel head coil. The data acquisition parameters of the T1 images are as follows: rapid gradient echo Magnetization-Prepared Rapid Gradient Echo sequence prepared by magnetisation (TR/TE/TI, 2000 ms/1.75 ms/450 ms; tilt angle, 15°; layer thickness, 1.0 mm) to obtain high-resolution T1-weighted anatomical images (Field of View=240×240×160 mm3; resolution matrix=256×256; voxel size=1×1×1 mm3). The resting state function NMR acquisition parameters are as follows: T2* weighted gradient echo plane imaging sequence to obtain 180 volumes (number of layers/TR/TE/rotation angle=32/2000 ms/30 ms/90°, matrix=64×64, FOV=230×230×128 mm3, voxel size=3.52×3.52×3.5 mm3). Scanning time is 6 min.

Patient safety and adherence

All adverse events (eg, pain and falls) that occur during the intervention and follow-up will be recorded on the case record form (CRF) via the way of the monitor and self-report and will be evaluated for relevance to the intervention. The occurrence rate of the adverse event was defined as the number of occurred participants divided by all participants (T1).

The following are some key strategies that can be used to improve adherence. (1) Education and communication: provide patients with clear, concise and comprehensive information about the intervention, its purpose, benefits and expected outcomes. (2) Support and motivation: provide emotional or financial support and encouragement to patients to maintain their motivation to adhere to the intervention; work with community organisations and social services to provide additional support. This research project will cover the cost of acupuncture, tDCS treatments and assessments performed during the participant’s participation in this study. Hence, this study can appropriately reduce the financial burden on participants. (3) Collaborative care: provide training and education for family members and caregivers to support patient adherence. Our group will invite a clinician who has been working for >10 years to give health education courses to the participants and caregivers once a month, either face-to-face or online.

Data management and monitoring

Two research assistants, who are unaware of the research process, will enter all data collected into the online data management system by double entry. Data checks (eg, CRF checks with raw data, double-checking) will be performed to ensure data accuracy before descriptive and statistical analyses are performed. Access to datasets will be limited to the Clinical Trial Management and Data Safety and Monitoring Committees.31 Storage and handling of hard copies of study data will be in strict accordance with the regulations and policies of the investigator’s institution and study site. In addition, serious adverse events will be reported to an independent Data Safety and Monitoring Committee, which will recommend whether to continue, modify or discontinue the intervention. During the study, datasets will be stored, analysed and archived under a pseudonym to protect the privacy of individuals.

Statistical analysis

All statistical analyses will be performed using IBM SPSS V.20.0. Outcome analyses are conducted on an intention-to-treat basis and missing data will be entered using multiple entry methods. Shapiro–Wilk tests will be used to test the normal distribution of continuous variables for demographic and outcome measures. Continuous variables will be described as mean±SD for normal distributions and median for non-normal distributions; categorical variables will be described as frequencies. χ2 tests or Fisher exact tests will be used to examine comparisons of categorical variables between the three groups. A two-way ANOVA with repeated measures will be used to examine the main effect of the group, the time factor and the group–time interaction effect. Simple effects post-hoc analyses will be conducted when time–group interactions are significant. The significance level for all statistical tests will be set at 0.05 and corrected for multiple comparisons using the Bonferroni correction method.

Patient and public involvement

The initial research idea was proposed by the research team. Patients with poststroke shoulder pain, physiotherapists and neurorehabilitation physicians were involved in the preparation of the proposal through face-to-face interviews. Additionally, the study protocol will be revised by the research team and all issues not addressed in the draft proposed at that time will be added based on their feedback to ensure the safety and applicability of the intervention.

Ethics and dissemination

All study procedures were in accordance with the current version of the Declaration of Helsinki (see www.wma.net for details) and relevant ethical guidelines. Ethical approval was obtained from the Research Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (No. 2023KY-039–001). The research team will communicate information about the study to recruited participants, including the purpose of the study, recruitment criteria, study protocol, potential risks and expected functional benefits. Informed consent will be obtained from patients who are eligible and choose to participate in the trial at a clinical research facility. Participants will be informed that they can withdraw from the study at any time without consequence. The results of the study will be published in peer-reviewed scientific journals and presented at conferences and seminars within 12 months of completion of the study.

Discussion

Poststroke shoulder pain and the resulting upper limb dysfunction remain a neglected problem, which can negatively affect clinical outcomes. Current evidence focuses on the use of a single approach to the treatment of poststroke shoulder pain, whereas, in actual clinical practice, multiple treatments are often chosen for simultaneous intervention with the expectation of improving patient outcomes. Therefore, research into combined therapeutic approaches for poststroke shoulder pain is urgent, and developing an ideal and effective rehabilitation programme is still ongoing.

This is the first clinical trial to study the combination of tDCS and acupuncture in treating patients with poststroke shoulder pain. The effectiveness of these interventions will be explored by designing a 4-week intervention and a 6-month follow-up. This research protocol will provide guidance on the importance of integrating existing and different rehabilitation techniques and designing more effective rehabilitation programmes.

The combination of tDCS enables patients with poststroke to maximise motor and functional recovery of the paralysed upper limbs and achieve independence in activities of daily living at an early stage, while also helping to maintain these results over time.32 33 The combined application of tDCS to patients with stroke not only accelerates functional recovery but also improves it, and the effects are maintained up to 1-year poststroke.34 It is unclear whether the combination of tDCS and acupuncture has a synergistic effect on improving poststroke shoulder pain, and the possible central mechanisms are unknown.

fMRI can objectively reflect cerebral nerve function, local blood flow status of the brain and brain tissue metabolism, reflecting the changes in cerebral neuroplasticity and has been widely used in recent years in the study of mechanisms of neurological diseases.35 36 Acupuncture stimulation of different regions can affect reflex circuits in the nervous system, establish new synaptic connections, promote neuronal synaptic regeneration and integrate central nervous system functions, thus improving the dysfunction of stroke patients. Acupuncture can induce a wide range of changes in brain activity, confirming the effects of acupuncture on the recovery of neurological function in stroke patients and that these changes in action are related to the neuroplasticity of acupuncture.28 37 The tDCS treatment of various chronic pain regulates cortical function by inducing cerebral neuroplasticity and affects the level of membrane potential and firing rates of target cortical neurons. tDCS changes, which are mainly manifested in the human motor cortex, such as the primary motor cortex (area M1), can alleviate the pain of the patients by altering the excitability of the cerebral cortex.38 39 Changes in neuroplasticity in the brain of patients with poststroke shoulder pain treated with tDCS combined with acupuncture have been observed by fMRI.

This study has a number of strengths. First, the intervention programme used in this study will be evidence-based and rigorously developed in accordance with the evidence, recommendations, theories and practice standards of systematic evaluation. Second, sensitive, systematic and comprehensive validated evaluation results were selected. These range from subjective pain and psychological scales to objective functional assessment scales and fMRI tests, combining subjectivity and objectivity to reduce the bias of confounding factors. Finally, fMRI was used to reveal the possible central mechanism of action in treating shoulder pain after stroke.

This research protocol may help to elucidate the interaction between tDCS and acupuncture. This new area of research may lead to the discovery of a central mechanism of action in the efficacy of tDCS and acupuncture in the treatment of poststroke shoulder pain, and potentially to the development of new therapeutic strategies aimed at improving the efficacy of treating poststroke shoulder pain. Therefore, this study will provide a more comprehensive and systematic protocol for further subsequent RCT studies.

This study protocol also has some limitations. Due to the visibility of the intervention, the design could not be blinded to participants and study researchers in the current study protocol. The source of data for the collection of cases was a single healthcare facility only, and there was a lack of multicentre healthcare facility data, which affected the level of evidence for the study findings. This study also lacks long-term follow-up and evaluation, and the long-term effects of the intervention are unknown. The shortcomings of acupuncture treatment are that it requires specialised doctors to administer the treatment and varies to some extent from doctor to doctor. There is also a lack of analysing the cost-effectiveness and cost-utility of tDCS combined with acupuncture for the treatment of poststroke shoulder pain. tDCS combined with acupuncture may increase the cost of treatment while improving clinical efficacy. We need to evaluate the cost inputs and health outputs of tDCS combined acupuncture from a health economics perspective in the future.

With this trial, we aim to test the hypothesis that tDCS combined with acupuncture treatment in patients with poststroke shoulder pain, when treated with conventional rehabilitation as a base treatment, not only improves pain and shoulder mobility in patients with poststroke shoulder pain but also improves the quality of daily life by improving the functional status of the upper limb. The positive results of this study will stimulate further large-sample-size, multicentre and even internationally collaborative RCTs that also include other types of dysfunction in stroke, potentially improving patient quality of life and expanding the number of patients who suffer from poststroke shoulder pain. In conclusion, the results of this study will demonstrate the effectiveness of tDCS combined with acupuncture treatment in patients with poststroke shoulder pain. More importantly, this study will investigate whether there is a synergistic enhancement of the effect of the combination of tDCS and acupuncture intervention and further explore its possible central mechanism of action.

Trial status

The trial is ongoing and recruiting participants. This study protocol is version 1 made on 28 September 2023. Recruitment commenced in December 2023 at the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine and is expected to be completed in December 2026.

Acknowledgements

This study was supported by the Rehabilitation Hospital affiliated to Fujian University of Traditional Chinese Medicine, the Rehabilitation Technology Key Laboratory of Fujian Province and the College of Rehabilitation Medicine of Fujian University of Traditional Chinese Medicine. We thank all those who supported this research.

Review Process File
10 09 2024

Funding: This work was supported by the National Key Research and Development Program of China (Grant Nos: 2022YFC2009700), the National Natural Science Foundation of China (82074513), the Natural Science Foundation of Fujian Province (No: 2020J01760) and the Fujian Province University Industry University Cooperation Project (No: 2021Y4017).

Prepublication history for this paper is available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2024-083986 ).

Patient consent for publication: Not applicable.

Provenance and peer review: Not commissioned; externally peer reviewed.

Patient and public involvement: Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research. Refer to the Methods section for further details.
==== Refs
References

1 de Sire A Moggio L Demeco A et al Efficacy of rehabilitative techniques in reducing hemiplegic shoulder pain in stroke: Systematic review and meta-analysis Ann Phys Rehabil Med 2022 65 S1877-0657(21)00119-6 10.1016/j.rehab.2021.101602
2 Zhang J Mao H Gao F et al Comparative study of ultrasonic-guided betamethasone local injection and extracorporeal shock wave therapy in post-stroke hemiplegic shoulder pain: a randomized clinical trial Front Neurol 2023 14 1158500 10.3389/fneur.2023.1158500 37538259
3 Li C Shu X Liu X Research hotspots and frontiers in post stroke pain: A bibliometric analysis study Front Mol Neurosci 2022 15 905679 10.3389/fnmol.2022.905679 35645732
4 Marotta N Demeco A Moggio L et al The adjunct of transcranial direct current stimulation to Robot-assisted therapy in upper limb post-stroke treatment J Med Eng Technol 2021 45 494 501 10.1080/03091902.2021.1922527 34038313
5 Lau SCL Connor LT Skidmore ER et al The moderating role of motivation in the real-time associations of fatigue, cognitive complaints, and pain withdepressed mood among stroke survivors: An ecological momentary assessment study Arch Phys Med Rehabil 2023 104 761 8 10.1016/j.apmr.2022.11.012 36535421
6 Tan B Jia L Ultrasound-guided BoNT-A (Botulinum Toxin A) injection Into the subscapularis for hemiplegic shoulder pain: A randomized, double-blind, placebo-controlled trial Stroke 2021 52 3759 67 10.1161/STROKEAHA.121.034049 34470492
7 Zhao J Chau JPC Chan AWK et al Tailored sitting Tai Chi program for subacute stroke survivors: A randomized controlled trial Stroke 2022 53 2192 203 10.1161/STROKEAHA.121.036578 35387494
8 Kmietowicz Z Offer exercise, therapy, acupuncture, or antidepressants for chronic primary pain, says NICE BMJ 2021 373 907 10.1136/bmj.n907
9 Liao H-Y Satyanarayanan SK Lin Y-W et al Clinical efficacy and immune effects of acupuncture in patients with comorbid chronic pain and major depression disorder: A double-blinded, randomized controlled crossover study Brain Behav Immun 2023 110 339 47 10.1016/j.bbi.2023.03.016 36948325
10 Li PS Peng XM Niu XX et al Efficacy of acupuncture for endometriosis-associated pain: a multicenter randomized single-blind placebo-controlled trial Fertil Steril 2023 119 815 23 10.1016/j.fertnstert.2023.01.034 36716811
11 Huang T Yao H Huang J et al Effectiveness of acupuncture for pain relief in shoulder-hand syndrome after stroke: a systematic evaluation and Bayesian network meta-analysis Front Neurol 2023 14 10.3389/fneur.2023.1268626
12 Zhan J Luo Y Mao W et al Efficacy of acupuncture versus rehabilitation therapy on post-stroke shoulder pain: A systematic review and meta-analysis of randomized controlled trials Medicine (Baltimore) 2023 102 e34266 10.1097/MD.0000000000034266 37478239
13 Zhan J Wei X Tao C et al n.d. Effectiveness of acupuncture combined with rehabilitation training vs. rehabilitation training alone for post-stroke shoulder pain: A systematic review and meta-analysis of randomized controlled trials Front Med 9 947285 10.3389/fmed.2022.947285
14 Zhan J Ai Y Zhan L et al Effect of abdominal acupuncture combined with routine rehabilitation training on shoulder-hand syndrome after stroke: A randomized controlled trial Integr Med Res 2022 11 100805 10.1016/j.imr.2021.100805 34877254
15 Zheng J Wu Q Wang L et al A clinical study on acupuncture in combination with routine rehabilitation therapy for early pain recovery of post-stroke shoulder-hand syndrome Exp Ther Med 2018 15 2049 53 10.3892/etm.2017.5659 29434804
16 Birch S Robinson N Acupuncture as a post-stroke treatment option: A narrative review of clinical guideline recommendations Phytomedicine 2022 104 S0944-7113(22)00376-2 10.1016/j.phymed.2022.154297
17 Muffel T Shih P-C Kalloch B et al Differential effects of anodal and dual tDCS on sensorimotor functions in chronic hemiparetic stroke patients Brain Stimul 2022 15 509 22 10.1016/j.brs.2022.02.013 35248785
18 Sehm B tDCS for motor stroke: The relevance of systematic comparisons Clin Neurophysiol 2017 128 1367 8 10.1016/j.clinph.2017.04.008 28527669
19 Andressa de Souza J Ferrari Corrêa JC Marduy A et al To combine or not to combine physical therapy with tDCS for stroke with shoulder pain? Analysis from a combination randomized clinical trial for rehabilitation of painful shoulder in stroke Front Pain Res (Lausanne) 2021 2 696547 10.3389/fpain.2021.696547 35295490
20 Molero-Chamizo A Salas Sánchez Á Álvarez Batista B et al Bilateral motor cortex tDCS effects on post-stroke pain and spasticity: A three cases study Front Pharmacol 2021 12 624582 10.3389/fphar.2021.624582 33967758
21 André-Obadia N Hodaj H Hodaj E et al Better fields or currents? A head-to-head comparison of transcranial Magnetic (rTMS) versus direct current dtimulation (tDCS) for neuropathic pain Neurotherapeutics 2023 20 207 19 10.1007/s13311-022-01303-x 36266501
22 Yao J Li X Zhang W et al Analgesia induced by anodal tDCS and high-frequency tRNS over the motor cortex: Immediate and sustained effects on pain perception Brain Stimul 2021 14 1174 83 10.1016/j.brs.2021.07.011 34371209
23 de Souza JA Corrêa JCF Agnol LD et al Effects of transcranial direct current stimulation on the rehabilitation of painful shoulder following a stroke: protocol for a randomized, controlled, double-blind, clinical trial Trials 2019 20 165 10.1186/s13063-019-3266-y 30876431
24 Molassiotis A Dawkins B Longo R et al Economic evaluation alongside a randomised controlled trial to assess the effectiveness and cost-effectiveness of acupuncture in the management of chemotherapy-induced peripheral neuropathy Acupunct Med 2021 39 41 52 10.1177/0964528420920285 32404001
25 Hsu S-P Lu C-F Lin B-F et al Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial J Neuroeng Rehabil 2023 20 27 10.1186/s12984-023-01153-4 36849990
26 Glize B Cook A Benard A et al Early multidisciplinary prevention program of post-stroke shoulder pain: A randomized clinical trial Clin Rehabil 2022 36 1042 51 10.1177/02692155221098733 35505589
27 Lu M Du Z Zhao J et al Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study Front Neurosci 2023 17 1143239 10.3389/fnins.2023.1143239 37274194
28 Lv Q Xu G Pan Y et al Effect of acupuncture on neuroplasticity of stroke patients with motor dysfunction: A meta-analysis of fMRI studies Neural Plast 2021 2021 8841720 10.1155/2021/8841720 34188677
29 Chan A-W Tetzlaff JM Gøtzsche PC et al SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials BMJ 2013 346 e7586 10.1136/bmj.e7586 23303884
30 Lai MH Xu HC Huang MC et al Transcranial direct current stimulation combined with bodyweight support-tai chi footwork for motor function of stroke survivors: a study protocol of randomised controlled trial BMJ Open 2023 13 e065338 10.1136/bmjopen-2022-065338
31 Van Norman GA Data safety and monitoring boards should be required for both early- and late-phase clinical trials JACC Basic Transl Sci 2021 6 887 96 10.1016/j.jacbts.2021.09.005 34869954
32 Garrido M M Álvarez E E Acevedo P F et al Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: A randomized, multicentre, double-blind, clinical trial Brain Stimul 2023 16 40 7 10.1016/j.brs.2022.12.008 36584748
33 Bolognini N Russo C Souza Carneiro MI et al Bi-hemispheric transcranial direct current stimulation for upper-limb hemiparesis in acute stroke: a randomized, double-blind, sham-controlled trial Eur J Neurol 2020 27 2473 82 10.1111/ene.14451 32697879
34 Bornheim S Croisier J-L Maquet P et al Transcranial direct current stimulation associated with physical-therapy in acute stroke patients - A randomized, triple blind, sham-controlled study Brain Stimul 2020 13 329 36 10.1016/j.brs.2019.10.019 31735645
35 Peng X Baker-Vogel B Sarhan M et al Left or right ear? A neuroimaging study using combined taVNS/fMRI to understand the interaction between ear stimulation target and lesion location in chronic stroke Brain Stimul 2023 16 1144 53 10.1016/j.brs.2023.07.050 37517466
36 Kolskår KK Richard G Alnaes D et al Reliability, sensitivity, and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors Hum Brain Mapp 2021 42 1167 81 10.1002/hbm.25284 33216408
37 Wang Y Wang L Wang Y et al Sensorimotor responses in post-stroke hemiplegic patients modulated by acupuncture at yanglingquan (GB34): A fMRI study using intersubject functional correlation (ISFC) analysis Front Neurol 2022 13 900520 10.3389/fneur.2022.900520 35734477
38 Gregoret L Zamorano AM Graven-Nielsen T Multifocal tDCS targeting the motor network modulates event-related cortical responses during prolonged pain J Pain 2023 24 226 36 10.1016/j.jpain.2022.09.010 36162791
39 Xiong HY Zheng JJ Wang XQ Non-invasive brain stimulation for chronic pain: state of the art and future directions Front Mol Neurosci 2022 15 888716 10.3389/fnmol.2022.888716 35694444
