Efficacy And Central Mechanism of Acupuncture Treatment In Patients With Neck Pain: Study Protocol For A Randomized Controlled Trial

Efficacy And Central Mechanism of Acupuncture Treatment In Patients With Neck Pain: Study Protocol For A Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy And Central Mechanism of Acupuncture Treatment In Patients With Neck Pain: Study Protocol For A Randomized Controlled Trial Zhen Gao, Tao Yin, Lei Lan, Dehua Li, Ruirui Sun, Guodong Ha, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-377610/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Aug, 2021 Read the published version in Trials → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Acupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP. This study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI). Methods: This is a randomized controlled trial, 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, the pressure pain threshold, etc. will be used to evaluate clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analysed, respectively. Pearson correlation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms. Discussion: The results might provide further evidence for the clinical application of acupuncture in the treatment of NP. Trial registration : Chinese Clinical Trial Registry, ChiCTR2000040930. Registered on December 16, 2020. Translational Medicine Internal Medicine Integrative & Complementary Medicine Neck pain Acupuncture Central mechanism Functional magnetic resonance imaging Protocol Figures Figure 1 Figure 2 Background Neck pain (NP), as a common musculoskeletal disorder, has become an important healthcare and social problem due to its high prevalence and heavy economic burden. 1 It is estimated that more than 30% of the population suffer from NP every year, 2 and its lifetime prevalence in adults ranges from 14.2–71%. 3 Due to the increasing prevalence of NP, the health care costs of NP have rapidly increased. 4 – 6 In the United States, the cumulative annual cost for treating lower back pain and NP is $ 87.6 billion. 7 The treatment of NP has been challenging, because its etiology is complex and the symptoms are easy to recur. Although medications (e.g. muscle relaxants and non-steroidal anti-inflammatory drugs) are effective in alleviating acute pain, their side effects, including hepatotoxicity, etc. cannot be ignored. 8 Therefore, more patients tend to purchase non-drug therapies to relieve symptoms. Acupuncture has been used to relieve pain for thousands of years in China. As early as 1997, the National Institutes of Health (NIH) had identified pain as one of the dominant diseases for acupuncture. Recently, some large-scale clinical studies confirmed the efficacy of acupuncture in improving NP symptoms. 9 – 11 However, the underlying mechanisms of acupuncture for NP have not been fully elucidated. Advances in neuroimaging techniques have enhanced studies into the central mechanisms of acupuncture as an analgesic in vivo . In the last two decades, many neuroimaging studies have been performed to elucidate the mechanisms of acupuncture analgesia, and achieved gratifying results. 12 – 15 For example, an fMRI study on migraines found that acupuncture was effective in improving abnormally reduced functional activity in the rostral ventromedial medulla/trigeminocervical complex area of patients. 16 Recently, significant alterations in both brain structure and function of NP patients have been reported by neuroimaging studies. Compared to healthy subjects, NP patients shown decreased functional activity in the left sensorimotor cortex and right temporoparietal junction, 17 as well as increased functional connectivity between the right dorsolateral prefrontal cortex and the right anterior insula, which are associated with pain intensity. 18 Based on these findings, the utilization of neuroimaging techniques to investigate the central mechanisms of acupuncture treatment of NP is practical and feasible. Therefore, by fMRI, this study aims at: 1) evaluating the therapeutic effects of different acupoints prescription on NP; and 2) investigating the cerebral activity changes elicited by acupuncture treatment; and 3) analyzing the possible correlations between the improvement of clinical symptoms and changes in brain activity, so as to explore the potential central mechanism of acupuncture for NP. Methods Design This is a randomized controlled trial. The protocol was drawn up in accordance with the Consolidated Standards of Reporting Trials guidelines and the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines (STRICTA). 19 20 The protocol has been approved by the Institutional Review Board of the Hospital of Chengdu University of Traditional Chinese Medicine (approved number: 2020KL-007) and registered at Chinese Clinical Trial Registry (registration number: ChiCTR2000040930, protocol version number: V1.0). This study period last for 16 weeks, which included a 2-week baseline period, a 2-week intervention period, and a 12-week following period. A total of 86 patients with NP will be randomly assigned to the two acupuncture groups with a 1:1 ratio. 20 patients in each group will be randomly selected to undertake fMRI scans. Clinical outcome evaluation and fMRI scans will be conducted at baseline and after treatment. The study procedure is outlined in Fig. 1 and Table 1 . Table 1 Study schedule for data collection. Period Baseline Treatment Follow-up Assessment 1 2 3 4 Time (week) 0 2 3 4 8 16 Pick-up information Inclusion/exclusion criteria √ Informed consent √ Vital signs √ Medical history √ Physical examination √ √ Acupuncture intervention Group A (n = 43) √ √ √ √ √ √ Group B (n = 43) √ √ √ √ √ √ Clinical assessment VAS √ √ √ √ √ NDI √ √ √ √ ROM √ √ √ √ √ PPT √ √ √ √ SF-36 √ √ √ √ MSUS √ √ SAS and SDS √ √ √ √ fMRI (n = 40) √ √ Laboratory test √ √ Adverse event √ This is a randomized controlled trial of neuroimaging including a 2-week baseline period, a 2-week treatment period, and a 12-week follow-up period. At baseline, participants will be screened based on inclusion and exclusion criteria; eligible individuals will then sign informed consent and undergo a physical examination. After randomized into 2 groups, 6 acupuncture treatments will be performed for 2 weeks. Clinical data will be evaluated at baseline, after treatment ends, and at 4 and 12 weeks after completion, fMRI scans will be performed before the first and sixth acupunctures. After the treatment, laboratory tests will be performed, including routine blood test, C-reactive protein, and erythrocyte sedimentation tests. Adverse events will be recorded in the CRF at any time during treatment. fMRI functional magnetic resonance imaging, VAS Visual Analogue Acales, NDI Neck Disability Index, ROM Cervical Range of Motion, PPT Pressure Pain Threshords, MSUS musculoskeletal ultrasound, SF-36 short-form 36-item Health Survey, SAS Self-Rating Anxiety Scale, SDS Self-Rating Depression, CRF case report form Participants Recruitment procedures Patients will be recruited at the outpatient of the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) and Sichuan Integrated Medicine Hospital. In addition, patients will also be recruited from the community and campus of Chengdu University of TCM through advertising (posting notices, distributing leaflets, web publishing). Patients who agree to participate in this study will be diagnosed by an orthopedic specialist. The eligible patients will be screened by the research assistant based on the inclusion and exclusion criteria. Inclusion criteria Participants who match the inclusion criteria will be included: 1) those with NP as the main complaint and a visual analog scale (VAS) score of pain severity exceeding 4 points but less than 10 points (range 0–10 points); and 2) for a duration of ≤ 3 months; and 3) aged 18–60 years; and 4) agreeing to sign informed consent. Exclusion criteria Participants with any of the following conditions will be excluded: 1) they are pregnant or lactating women; or 2) they have any organic or metabolic diseases of the digestive, hematopoietic, endocrine, or immune systems, or other severe primary diseases; or 3) they have local skin damage or severe skin diseases that affect acupuncture manipulation; or 4) they combine with mental or neurological diseases; or 5) they have received acupuncture for NP within one month; or 6) they have MRI contraindications, such as heart pacemaker, metallic foreign bodies, or severe claustrophobia, etc.; or 7) they are participating in other clinical trials. Sample size This study aims to compare the difference of the clinical efficacy of two acupuncture prescriptions (Group A and Group B). According to the results of the pilot study, the average reduction of VAS score in Group A was 2.86 ± 0.99, and the average reduction of VAS score in Group B was 2.14 ± 0.99. According to the formula, , with α = 0.05 (both sides) and 1-β = 0.80. 21 The sample size of each group was calculated to be 34, considering a 20% dropout rate, the final sample size was set to 43 per group, making the total of 86 in this study. There is no widely accepted method for sample size calculation in neuroimaging study. Referring to the previous study, 22 15 participants in each group is the smallest size in neuroimaging studies. Considering a 20% dropout rate and the unavailability of data due to various reasons, this study will randomly select 20 patients from each group for fMRI scans. Randomization and blinding Randomization will be carried out in two steps: 1) an independent, blinded statistician will generate a random allocation sequence using SPSS 26.0 (IBM, Chicago, IL, USA). The 86 patients will be randomly assigned into Group A and Group B at a ratio of 1:1; 2) 20 patients from each group will be randomly selected for fMRI. Allocation concealment will be achieved by sequentially numbered, opaque, sealed envelopes. In this study, the patients, outcome assessors and statistical analysts will be blinded. The patients will be treated at the separate rooms to reduce communication. However, due to the particularity of acupuncture manipulation, blinding operator cannot be achieved. Interventions Patients in Group A will receive acupuncture at three acupoints (Lieque (LU7), Chize (LU5) and neck tenderness point on the affected side) (Fig. 2 A). The acupoints of Group B (control group) will receive acupuncture at three acupoints (Shaohai (HT3), Lingdao (HT4) and neck tenderness point on the affected side) (Fig. 2 B). Tenderness points will be detected using a PX25 hand-held pressure pain tester (Wagner FPX™ 25). The acupuncture manipulations are as follows: disposable sterile filiform needles (0.30 × 40 mm, Huatuo Medical Instrument Co.,Ltd., China) will be inserted into acupoints at a depth of 20–30 mm after skin disinfection, and the Deqi sensation (a sensation of acid distension or numbness, or other acupuncture sensation) will be achieved. 23 Then, HANS-200A acupoint nerve stimulator (Nanjing Jisheng Medical Technology Company, Nanjing city, China) will connect LU7 and LU5 of Group A or HT3 and HT4 of Group B respectively in the two groups for 30 minutes with dilatational waves (2-100 Hz, 1 mA). Patients will receive a total of 6 sessions of acupuncture in two weeks with 3 sessions per week. Acupuncture treatment will be performed by acupuncturists who have held a practitioner license for more than 3 years. Concomitant medications Patients will be instructed not to take any other analgesic medications for NP during this study. In cases of severe NP, ibuprofen (300 mg per capsule with sustained release) will be allowed as rescue medication and should be recorded on the case report form (CRF). Outcome measurements The measurements will be conducted by independent assessors who have been trained prior to the study. The primary outcome is the change of VAS scores for pain severity from baseline to 2 weeks. VAS scores range from 0 to 10, with 0 indicating no pain and 10 indicating pain is unbearable. The secondary outcome measurements including: Neck Disability Index (NDI), Short-Form 36-Item Health Survey (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Range of Motion (ROM) and Pressure Pain Threshold (PPT) will be evaluated at baseline, after treatment, and at 4 and 12 weeks after the end of treatment. In addition, we will perform musculoskeletal ultrasound (MSUS) before and after treatment. Among them, NDI is the most widely used clinical tool for self-assessment of disability caused by NP. 24 The SAS and SDS are the commonly used psychometric tools to measure the severity of anxiety and depression. 25 26 SF-36 is a general health-based survey of quality of life, which can be self-administered by the patient with reliability. 27 ROM is one of the quantitative outcomes assessing the extent and degree of joint motor impairment. The changes of the tenderness threshold can quantitatively reflect the improvement of the pain severity. 28 Meanwhile, MSUS is an important means for clinical diagnosis of rehabilitation medicine, tracking disease progression and assessing curative effect. 29 Patient safety Adverse events during treatment will be reported in the CRF. The record should include the time, reason, clinical symptoms, and signs of the adverse event, as well as the corresponding emergency treatment plan. MRI data acquisition The resting-state fMRI (RS-fMRI) will be performed at the baseline and the end of treatment, respectively. Patients will be asked to do not drink tea, coffee, or alcohol, avoid strenuous exercise, and ensure adequate sleep before the scan. Patients will undergo RS-fMRI scan with a 3.0T MR scanners (Siemens 3T Tim trio, Erlangen, Germany) at the West China Hospital of Sichuan University. Patients will be asked to stay awake and to keep their heads still during the scan, with their eyes closed and ears plugged. Scans will be performed with the following procedures: localizer, three-dimensional T1-weighted imaging (3D-T1WI), blood oxygenation level-dependent fMRI (BOLD-fMRI) and diffusion tensor imaging (DTI) sequence. The 3D-T1WI scanning parameters will be as follows: repetition time (TR) = 6.008 ms, echo time (TE) = 1.7 ms, data matrix = 256 × 256, field of view (FOV) = 256 × 256 mm 2 . The BOLD-fMRI scanning parameters will be as follows: 31 contiguous slices with a slice thickness of 5 mm, TR = 2000 ms, TE = 30 ms,FOV = 240 × 240 mm 2 , Matrix = 64 × 64, flip angle (FA) = 90°, total volumes = 240. The DTI data will be acquired using a single-shot echo planar image sequence with the following parameters: FOV = 256 × 256 mm 2 , TR = 8500 ms, matrix = 128 × 128, slice thickness = 2 mm with no gap. Two diffusion-weighted sequences were acquired using gradient values b = 1000 s/mm 2 and b = 0 s/mm 2 with the diffusion-sensitizing gradients applied in 64 non-collinear directions. Statistical analysis Clinical data analysis The comprehensive effectiveness analysis will use the per protocol set (PPS) and the full analysis set (FAS). The FAS population will be used as the primary population for all efficacy analyses. The safety set (SS) included all subjects who received at least one treatment after randomization. When the results of PPS analysis and FAS analysis are inconsistent, PPS and FAS are discussed separately to find out the reasons for the inconsistency. Missing data will be handled using the last-observation-carried-forward (LOCF) method. Statistical analysis will be conducted using SPSS 26.0 (IBM, Chicago, IL, USA) statistical software. P < 0.05 (two-sided) is considered statistically significant. Quantitative data are described with mean ± standard deviation (SD). Qualitative data are described with frequency and percentage (N, %). Student’s t- test and chi-square test will be used to compare the differences between groups at baseline. The primary outcome will be carried out with a paired samples t -test, and the secondary outcome will be compared at four timepoints using the repeated measures ANOVA. Clinical data on skewed distribution will be compared using a non-parametric test. MRI data analysis The fMRI data preprocessing and comparison will be performed using SPM12 software ( http://www.fil.ion.ucl.ac.uk/spm/ ) based on MATLAB 2018a (Mathworks, Inc., USA). The steps including: format conversion, slice timing correction, head motion correction, spatial standardization, linear trend removal, spatial smoothing, and band-pass filtering. After pre-processing, the amplitude of low frequency fluctuation and regional homogeneity will be calculated to reflect the local cerebral functional activity, and the seeds-based functional connection analysis will be performed to reflect the functional integration of the brain. ANOVA will be used for comparisons between the two groups, with multiple comparison corrections. Furthermore, the Pearson correlation analysis will be conducted to assess the associations between the changes of fMRI and the improvement of clinical symptoms. Discussion To the best of our knowledge, this is the first randomized controlled study that is aimed at investigating the clinical efficacy and underlying mechanisms of different acupuncture prescriptions for NP. The results of this study are beneficial for the prescription selection of acupuncture for treating NP, and elucidates on the mechanisms of acupuncture for NP. Selection of acupoint prescription Many clinical studies have been performed on acupuncture for NP, and its efficacy has been identified. In clinical practice, the combination of local and distal points is a basic principle of acupoint prescriptions, but the number of prescriptions and acupoints involved is enormous. Therefore, in this study, two different prescriptions will be selected to compare their efficacy and possible mechanisms. Neck tenderness point will be selected as the basic acupoint, which is the most commonly used local acupoint in NP’ treatment. LU7 and LU5, located in the forearm, will be selected as distal points in Group A. HT4 and HT3, also located in the forearm, will be selected as distal points in Group B. All these distal points are reported to be effective in some clinical trials on acupuncture for treating NP. 30–32 The combination of subjective and objective outcome measures Pain is an unpleasant sensory and emotional perception that is associated with actual or underlying tissue pathology. 33 Human behavior, psychological and social factors play a crucial role in the long-term maintenance of pain. 34 Therefore, the multidimensional nature of pain requires that the measurement of NP should include both subjective outcomes and objective outcomes. In this study, subjective outcomes including VAS, NDI, SAS and SDS will be used to assess pain perception, dysfunction, and emotional state of the patients. Moreover, objective outcomes including tenderness threshold, musculoskeletal ultrasound and ROM will be used to evaluate the improvement of symptoms in NP patients. The combination of subjective and objective outcomes can be more complementary to assess the efficacy from multiple perspectives and reduce the occurrence of potential bias, so as to improve the quality of clinical evidence. Application of neuroimaging technology Previous neuroimaging studies have demonstrated that patients with NP present with abnormalities in brain activity and structure. For example, Chen et al. 35 found increased spontaneous brain activity in the supplementary motor area of NP patients, and subsequently suggested a correlation between abnormality of the salience network with the disease. Another single fMRI-based case control study associated NP with activation and/or recall of pain memory. 36 Elsewhere, a voxel-based morphometry study performed on NP patients revealed that the loss of bilateral clusters of gray matter in the sensorimotor cortex and pulvinar nucleus with NP pathophysiology. 37 Moreover, it has been reported that central integration is the key determinant of the effectiveness of acupuncture. 38 With previous studies, performed on individuals with shoulder pain, 39 fibromyalgia, 40 and low back pain, 41 as well as knee osteoarthritis 12 indicating that regulation of brain activity might be an important factor influencing acupuncture’s modulating effects on pain. For example, acupuncture has been shown to effectively reduce pain by modulating brain regions related to both sensory-discriminative and emotional aspects. 42 Such regions were found to be important for the therapeutic effects of acupuncture on NP. 35 Based on these evidences, we hypothesize that acupuncture can effectively treat NP by modulating alteration of brain activity. This trial is the first study to use fMRI to explore the potential central mechanisms of different acupuncture prescriptions for the treatment of NP. The results of this trial will help to provide visualization evidence for the clinical application of acupuncture for NP treatment. Trial Status The trial is currently in the recruitment phase and the study is expected to end in December 2021. Abbreviations 3D-T1WI Three-dimensional T1-weighted imaging BOLD-fMRI Blood oxygenation level-dependent fMRI RS-fMRI Resting state functional magnetic resonance imaging CRF Case report form DTI Diffusion tensor imaging FA Flip angle FAS Full analysis set FDR False Discovery Rate FOV Field of view GLM General Linear Model HbO Oxygenated hemoglobin HbR Deoxygenated hemoglobin LOCF Last observation carry-forward MRI Magnetic resonance imaging MSUS Musculoskeletal ultrasound NDI Neck Disability Index NP Neck Pain NIH National Institutes of Health PPS Per protocol set PPT Pressure pain threshold ROM Range of motion SD Standard Deviation SF-36 Short-form 36-item Health Survey SAS Self-Rating Anxiety Scale SDS Self-Rating Depression SS Safety set TCM Traditional Chinese Medicine TE Echo time TR Repetition time VAS Visual Analogue Scale Declarations Ethics approval and consent to participate This trial has been approved by the Institutional Review Boards and Ethics Committees of the First Teaching Hospital of CDUTCM (Approved number: 2020KL-007) and has been registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000040930). Only patients who have signed the informed consent form will be included. Ethics and dissemination Ethical approval of this study has been approved by the Ethics Committee of the Hospital of Chengdu University of Traditional Chinese Medicine (No. 2020KL-007). The outcomes of the trial will be disseminated through peer-reviewed publications. Consent for publication Not applicable. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding The study is financially supported by the National Key Research and Development Program in China (2018YFC1704606). Authors’ contributions FZ and LJ are responsible for this study. FZ, LJ, ZG, TY, and LL conceived and designed the study. ZG, TY, and LL participated in drafting the trial protocol and preparing the manuscript. SR, LD, HG, JC, and HZ participated in data collection and were in charge of recruitment and treatment of patients. All authors read and approved the final manuscript. Acknowledgments We thank Haifa Qiao and Gang Lu for the help of participants enrollment. References Safiri S, Kolahi AA, Hoy D, et al. Global, regional, and national burden of neck pain in the general population, 1990-2017: systematic analysis of the Global Burden of Disease Study 2017. BMJ (Clinical research ed) 2020;368:m791. doi: 10.1136/bmj.m791 [published Online First: 2020/03/29] Cohen SP. Epidemiology, diagnosis, and treatment of neck pain. Mayo Clinic proceedings 2015;90(2):284-99. doi: 10.1016/j.mayocp.2014.09.008 [published Online First: 2015/02/11] Fejer R, Kyvik KO, Hartvigsen J. The prevalence of neck pain in the world population: a systematic critical review of the literature. 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Default Mode Network as a Neural Substrate of Acupuncture: Evidence, Challenges and Strategy. Frontiers in neuroscience 2019;13:100. doi: 10.3389/fnins.2019.00100 [published Online First: 2019/02/26] Yan CQ, Huo JW, Wang X, et al. Different Degree Centrality Changes in the Brain after Acupuncture on Contralateral or Ipsilateral Acupoint in Patients with Chronic Shoulder Pain: A Resting-State fMRI Study. Neural plasticity 2020;2020:5701042. doi: 10.1155/2020/5701042 [published Online First: 2020/05/08] Mawla I, Ichesco E, Zöllner HJ, et al. Greater Somatosensory Afference with Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular GABA: A Randomized Neuroimaging Trial. Arthritis & rheumatology (Hoboken, NJ) 2020 doi: 10.1002/art.41620 [published Online First: 2020/12/15] Makary MM, Lee J, Lee E, et al. Phantom Acupuncture Induces Placebo Credibility and Vicarious Sensations: A Parallel fMRI Study of Low Back Pain Patients. Scientific reports 2018;8(1):930. doi: 10.1038/s41598-017-18870-1 [published Online First: 2018/01/19] Yu SW, Lin SH, Tsai CC, et al. Acupuncture Effect and Mechanism for Treating Pain in Patients With Parkinson's Disease. Frontiers in neurology 2019;10:1114. doi: 10.3389/fneur.2019.01114 [published Online First: 2019/11/07] Supplementary Files SPIRIT.doc Cite Share Download PDF Status: Published Journal Publication published 14 Aug, 2021 Read the published version in Trials → Version 1 posted Editorial decision: Major revision 11 Jun, 2021 Reviews received at journal 21 May, 2021 Reviewers invited by journal 21 May, 2021 Editor assigned by journal 03 May, 2021 First submitted to journal 29 Mar, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-377610","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":28657338,"identity":"e9086de9-ae6c-44a3-8855-90417cb5cacf","order_by":0,"name":"Zhen Gao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIie3QsQrCMBCA4YRAXE5cWyjkFeJerG/gK0QKTn2ISNaAs/gezhccXIquhS59hGZzEtvF+UbB/NMN93EkjKVSPxm3aKCE1cKSiQg4FIci90gmsg5DeSt1tyUCtWs1muYJrGN8jA2BrHEmbQ/8YkV+vlLI0Wvc+x5EgVIsScTBRN4PkJkhEiWlmT4ZAchEg8CJ1JBBcLS3qFNw8QWbqrq7MEbSFfyO3BL25yvEvVQqlfrnPjq6OTALoJLnAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-8410-8630","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Gao","suffix":""},{"id":28657339,"identity":"adbdc33a-c327-4c63-b4f9-5979f9d4d7a9","order_by":1,"name":"Tao Yin","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Yin","suffix":""},{"id":28657340,"identity":"276c2555-c322-43a7-8c8a-8ded64a8b573","order_by":2,"name":"Lei Lan","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine Wenjiang Campus: Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Lan","suffix":""},{"id":28657341,"identity":"206842ea-0fe4-426b-ab16-650a6979f180","order_by":3,"name":"Dehua Li","email":"","orcid":"","institution":"Hopital of Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dehua","middleName":"","lastName":"Li","suffix":""},{"id":28657342,"identity":"d11b7f01-10d6-4a55-ac1b-792cb430cf6c","order_by":4,"name":"Ruirui Sun","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruirui","middleName":"","lastName":"Sun","suffix":""},{"id":28657343,"identity":"13a4b039-c2aa-4a86-ba39-9b464042d76b","order_by":5,"name":"Guodong Ha","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guodong","middleName":"","lastName":"Ha","suffix":""},{"id":28657344,"identity":"c84e1220-0d7b-4a5b-b9e6-c4b64a1eaaa4","order_by":6,"name":"Caili Jiang","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Caili","middleName":"","lastName":"Jiang","suffix":""},{"id":28657345,"identity":"c33bdc23-2ea5-49de-bacd-b00e550acc12","order_by":7,"name":"Xin Shao","email":"","orcid":"","institution":"Sichuan Integrated Medicine Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Shao","suffix":""},{"id":28657346,"identity":"86029aa6-2e1e-4223-9962-fd87d4f77bc7","order_by":8,"name":"Zhaoxuan He","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhaoxuan","middleName":"","lastName":"He","suffix":""},{"id":28657347,"identity":"73521e88-1d8e-448a-ab91-094e11ea128f","order_by":9,"name":"Laixi Ji","email":"","orcid":"","institution":"Shanxi University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laixi","middleName":"","lastName":"Ji","suffix":""},{"id":28657348,"identity":"c7878783-4cd3-4121-a930-400685692210","order_by":10,"name":"Fang Zeng","email":"","orcid":"","institution":"Chengdu University of Traditional Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Zeng","suffix":""}],"badges":[],"createdAt":"2021-03-30 16:28:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-377610/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-377610/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13063-021-05507-y","type":"published","date":"2021-08-14T15:06:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":9517224,"identity":"b821c35b-1f30-4ffa-a75d-77fc0ed4ab16","added_by":"auto","created_at":"2021-05-24 16:47:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":593066,"visible":true,"origin":"","legend":"Flowchart of the procedure through the trial.\nThe randomized controlled trial will enroll 86 eligible patients and divide them randomly into two groups at a 1: 1 ratio. 20 patients from each group will be randomly selected for fMRI data collection. During the 2-week treatment, the patient will receive 6 acupuncture treatments. Clinical assessment will be performed at 4 time points: baseline, end of treatment, and 6 and 14 weeks after completion. The fMRI will be performed before the first and sixth acupuncture. \nAbbreviations: fMRI functional magnetic resonance imaging","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-377610/v1/47ba5a6ce3fcc9d3020f9d86.png"},{"id":9517223,"identity":"4c591eb6-a035-4d65-9f7c-a29f2471e2f7","added_by":"auto","created_at":"2021-05-24 16:47:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":591271,"visible":true,"origin":"","legend":"Locations of acupoints.\nA: Locations of acupoints (Group A). Lieque (LU 7), on the radial side of the forearm, above the styloid process of the radius and 1.5 cun above the horizontal stripes of the wrist. Chize (LU 5), in the transverse elbow, the radial side of the biceps tendon is sunken.\nB: Locations of acupoints (Group B). Lingdao (HT 4), in the anterior area of the forearm, the radial side of the ulnar carpi flexor tendon is 1.5 cun above the transverse stripes of the carpal palm. Shaohai (HT 3), at the midpoint of the line between the medial end of the transverse line of the elbow and the medial epicondyle of the humerus.","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-377610/v1/0ac0c6e2f271fe47d5a2594f.png"},{"id":13694438,"identity":"f02cfc30-2208-45da-a83b-15de8ccdb34a","added_by":"auto","created_at":"2021-09-17 12:53:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":956549,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-377610/v1/6239effa-e07d-4eed-a273-e586b60d40f6.pdf"},{"id":9517226,"identity":"fb82d1ad-7601-4cce-9294-13756056762b","added_by":"auto","created_at":"2021-05-24 16:47:31","extension":"doc","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":163840,"visible":true,"origin":"","legend":"","description":"","filename":"SPIRIT.doc","url":"https://assets-eu.researchsquare.com/files/rs-377610/v1/f81f81c1edea35354785aaa6.doc"}],"financialInterests":"","formattedTitle":"\u003cp\u003eEfficacy And Central Mechanism of Acupuncture Treatment In Patients With Neck Pain: Study Protocol For A Randomized Controlled Trial\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eNeck pain (NP), as a common musculoskeletal disorder, has become an important healthcare and social problem due to its high prevalence and heavy economic burden.\u003csup\u003e \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e \u003c/sup\u003e It is estimated that more than 30% of the population suffer from NP every year,\u003csup\u003e \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e \u003c/sup\u003e and its lifetime prevalence in adults ranges from 14.2\u0026ndash;71%.\u003csup\u003e3\u003c/sup\u003e Due to the increasing prevalence of NP, the health care costs of NP have rapidly increased.\u003csup\u003e \u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e \u003c/sup\u003e In the United States, the cumulative annual cost for treating lower back pain and NP is \u003cspan\u003e$\u003c/span\u003e 87.6\u0026nbsp;billion.\u003csup\u003e \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e \u003c/sup\u003e The treatment of NP has been challenging, because its etiology is complex and the symptoms are easy to recur. Although medications (e.g. muscle relaxants and non-steroidal anti-inflammatory drugs) are effective in alleviating acute pain, their side effects, including hepatotoxicity, etc. cannot be ignored.\u003csup\u003e \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e \u003c/sup\u003e Therefore, more patients tend to purchase non-drug therapies to relieve symptoms.\u003c/p\u003e \u003cp\u003eAcupuncture has been used to relieve pain for thousands of years in China. As early as 1997, the National Institutes of Health (NIH) had identified pain as one of the dominant diseases for acupuncture. Recently, some large-scale clinical studies confirmed the efficacy of acupuncture in improving NP symptoms.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e However, the underlying mechanisms of acupuncture for NP have not been fully elucidated.\u003c/p\u003e \u003cp\u003eAdvances in neuroimaging techniques have enhanced studies into the central mechanisms of acupuncture as an analgesic \u003cem\u003ein vivo\u003c/em\u003e. In the last two decades, many neuroimaging studies have been performed to elucidate the mechanisms of acupuncture analgesia, and achieved gratifying results.\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e For example, an fMRI study on migraines found that acupuncture was effective in improving abnormally reduced functional activity in the rostral ventromedial medulla/trigeminocervical complex area of patients.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Recently, significant alterations in both brain structure and function of NP patients have been reported by neuroimaging studies. Compared to healthy subjects, NP patients shown decreased functional activity in the left sensorimotor cortex and right temporoparietal junction,\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e as well as increased functional connectivity between the right dorsolateral prefrontal cortex and the right anterior insula, which are associated with pain intensity.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Based on these findings, the utilization of neuroimaging techniques to investigate the central mechanisms of acupuncture treatment of NP is practical and feasible. Therefore, by fMRI, this study aims at: 1) evaluating the therapeutic effects of different acupoints prescription on NP; and 2) investigating the cerebral activity changes elicited by acupuncture treatment; and 3) analyzing the possible correlations between the improvement of clinical symptoms and changes in brain activity, so as to explore the potential central mechanism of acupuncture for NP.\u003c/p\u003e "},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eDesign\u003c/h2\u003e\n\u003cp\u003eThis is a randomized controlled trial. The protocol was drawn up in accordance with the Consolidated Standards of Reporting Trials guidelines and the Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines (STRICTA).\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e The protocol has been approved by the Institutional Review Board of the Hospital of Chengdu University of Traditional Chinese Medicine (approved number: 2020KL-007) and registered at Chinese Clinical Trial Registry (registration number: ChiCTR2000040930, protocol version number: V1.0).\u003c/p\u003e\n\u003cp\u003eThis study period last for 16 weeks, which included a 2-week baseline period, a 2-week intervention period, and a 12-week following period. A total of 86 patients with NP will be randomly assigned to the two acupuncture groups with a 1:1 ratio. 20 patients in each group will be randomly selected to undertake fMRI scans. Clinical outcome evaluation and fMRI scans will be conducted at baseline and after treatment. The study procedure is outlined in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eStudy schedule for data collection.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePeriod\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"6\" align=\"left\"\u003e\n\u003cp\u003eTreatment\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFollow-up\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAssessment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTime (week)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePick-up information\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"8\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInclusion/exclusion criteria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInformed consent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVital signs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedical history\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePhysical examination\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAcupuncture intervention\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGroup A (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGroup B (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eClinical assessment\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVAS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNDI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eROM\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePPT\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSF-36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMSUS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSAS and SDS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003efMRI (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLaboratory test\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAdverse event\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026radic;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003eThis is a randomized controlled trial of neuroimaging including a 2-week baseline period, a 2-week treatment period, and a 12-week follow-up period. At baseline, participants will be screened based on inclusion and exclusion criteria; eligible individuals will then sign informed consent and undergo a physical examination. After randomized into 2 groups, 6 acupuncture treatments will be performed for 2 weeks. Clinical data will be evaluated at baseline, after treatment ends, and at 4 and 12 weeks after completion, fMRI scans will be performed before the first and sixth acupunctures. After the treatment, laboratory tests will be performed, including routine blood test, C-reactive protein, and erythrocyte sedimentation tests. Adverse events will be recorded in the CRF at any time during treatment.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003efMRI functional magnetic resonance imaging, VAS Visual Analogue Acales, NDI Neck Disability Index, ROM Cervical Range of Motion, PPT Pressure Pain Threshords, MSUS musculoskeletal ultrasound, SF-36 short-form 36-item Health Survey, SAS Self-Rating Anxiety Scale, SDS Self-Rating Depression, CRF case report form\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eParticipants\u003c/h2\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003ch2\u003eRecruitment procedures\u003c/h2\u003e\n\u003cp\u003ePatients will be recruited at the outpatient of the Hospital of Chengdu University of Traditional Chinese Medicine (TCM) and Sichuan Integrated Medicine Hospital. In addition, patients will also be recruited from the community and campus of Chengdu University of TCM through advertising (posting notices, distributing leaflets, web publishing). Patients who agree to participate in this study will be diagnosed by an orthopedic specialist. The eligible patients will be screened by the research assistant based on the inclusion and exclusion criteria.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eInclusion criteria\u003c/h2\u003e\n\u003cp\u003eParticipants who match the inclusion criteria will be included: 1) those with NP as the main complaint and a visual analog scale (VAS) score of pain severity exceeding 4 points but less than 10 points (range 0\u0026ndash;10 points); and 2) for a duration of \u0026le;\u0026thinsp;3 months; and 3) aged 18\u0026ndash;60 years; and 4) agreeing to sign informed consent.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eExclusion criteria\u003c/h2\u003e\n\u003cp\u003eParticipants with any of the following conditions will be excluded: 1) they are pregnant or lactating women; or 2) they have any organic or metabolic diseases of the digestive, hematopoietic, endocrine, or immune systems, or other severe primary diseases; or 3) they have local skin damage or severe skin diseases that affect acupuncture manipulation; or 4) they combine with mental or neurological diseases; or 5) they have received acupuncture for NP within one month; or 6) they have MRI contraindications, such as heart pacemaker, metallic foreign bodies, or severe claustrophobia, etc.; or 7) they are participating in other clinical trials.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n\u003ch2\u003eSample size\u003c/h2\u003e\n\u003cp\u003eThis study aims to compare the difference of the clinical efficacy of two acupuncture prescriptions (Group A and Group B). According to the results of the pilot study, the average reduction of VAS score in Group A was 2.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99, and the average reduction of VAS score in Group B was 2.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99. According to the formula, \u003cimg src=\"data:image/png;base64,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\" alt=\"\" /\u003e, with \u0026alpha;\u0026thinsp;=\u0026thinsp;0.05 (both sides) and 1-\u0026beta;\u0026thinsp;=\u0026thinsp;0.80.\u003csup\u003e21\u003c/sup\u003e The sample size of each group was calculated to be 34, considering a 20% dropout rate, the final sample size was set to 43 per group, making the total of 86 in this study.\u003c/p\u003e\n\u003cp\u003eThere is no widely accepted method for sample size calculation in neuroimaging study. Referring to the previous study,\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e 15 participants in each group is the smallest size in neuroimaging studies. Considering a 20% dropout rate and the unavailability of data due to various reasons, this study will randomly select 20 patients from each group for fMRI scans.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eRandomization and blinding\u003c/h2\u003e\n\u003cp\u003eRandomization will be carried out in two steps: 1) an independent, blinded statistician will generate a random allocation sequence using SPSS 26.0 (IBM, Chicago, IL, USA). The 86 patients will be randomly assigned into Group A and Group B at a ratio of 1:1; 2) 20 patients from each group will be randomly selected for fMRI. Allocation concealment will be achieved by sequentially numbered, opaque, sealed envelopes.\u003c/p\u003e\n\u003cp\u003eIn this study, the patients, outcome assessors and statistical analysts will be blinded. The patients will be treated at the separate rooms to reduce communication. However, due to the particularity of acupuncture manipulation, blinding operator cannot be achieved.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003eInterventions\u003c/h2\u003e\n\u003cp\u003ePatients in Group A will receive acupuncture at three acupoints (Lieque (LU7), Chize (LU5) and neck tenderness point on the affected side) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). The acupoints of Group B (control group) will receive acupuncture at three acupoints (Shaohai (HT3), Lingdao (HT4) and neck tenderness point on the affected side) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). Tenderness points will be detected using a PX25 hand-held pressure pain tester (Wagner FPX\u0026trade; 25).\u003c/p\u003e\n\u003cp\u003eThe acupuncture manipulations are as follows: disposable sterile filiform needles (0.30 \u0026times; 40 mm, Huatuo Medical Instrument Co.,Ltd., China) will be inserted into acupoints at a depth of 20\u0026ndash;30 mm after skin disinfection, and the Deqi sensation (a sensation of acid distension or numbness, or other acupuncture sensation) will be achieved.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Then, HANS-200A acupoint nerve stimulator (Nanjing Jisheng Medical Technology Company, Nanjing city, China) will connect LU7 and LU5 of Group A or HT3 and HT4 of Group B respectively in the two groups for 30 minutes with dilatational waves (2-100 Hz, 1 mA). Patients will receive a total of 6 sessions of acupuncture in two weeks with 3 sessions per week.\u003c/p\u003e\n\u003cp\u003eAcupuncture treatment will be performed by acupuncturists who have held a practitioner license for more than 3 years.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eConcomitant medications\u003c/h2\u003e\n\u003cp\u003ePatients will be instructed not to take any other analgesic medications for NP during this study. In cases of severe NP, ibuprofen (300 mg per capsule with sustained release) will be allowed as rescue medication and should be recorded on the case report form (CRF).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003eOutcome measurements\u003c/h2\u003e\n\u003cp\u003eThe measurements will be conducted by independent assessors who have been trained prior to the study. The primary outcome is the change of VAS scores for pain severity from baseline to 2 weeks. VAS scores range from 0 to 10, with 0 indicating no pain and 10 indicating pain is unbearable. The secondary outcome measurements including: Neck Disability Index (NDI), Short-Form 36-Item Health Survey (SF-36), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Range of Motion (ROM) and Pressure Pain Threshold (PPT) will be evaluated at baseline, after treatment, and at 4 and 12 weeks after the end of treatment. In addition, we will perform musculoskeletal ultrasound (MSUS) before and after treatment. Among them, NDI is the most widely used clinical tool for self-assessment of disability caused by NP.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e The SAS and SDS are the commonly used psychometric tools to measure the severity of anxiety and depression.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e \u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e SF-36 is a general health-based survey of quality of life, which can be self-administered by the patient with reliability.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e ROM is one of the quantitative outcomes assessing the extent and degree of joint motor impairment. The changes of the tenderness threshold can quantitatively reflect the improvement of the pain severity.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Meanwhile, MSUS is an important means for clinical diagnosis of rehabilitation medicine, tracking disease progression and assessing curative effect.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003ePatient safety\u003c/h2\u003e\n\u003cp\u003eAdverse events during treatment will be reported in the CRF. The record should include the time, reason, clinical symptoms, and signs of the adverse event, as well as the corresponding emergency treatment plan.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003ch2\u003eMRI data acquisition\u003c/h2\u003e\n\u003cp\u003eThe resting-state fMRI (RS-fMRI) will be performed at the baseline and the end of treatment, respectively. Patients will be asked to do not drink tea, coffee, or alcohol, avoid strenuous exercise, and ensure adequate sleep before the scan.\u003c/p\u003e\n\u003cp\u003ePatients will undergo RS-fMRI scan with a 3.0T MR scanners (Siemens 3T Tim trio, Erlangen, Germany) at the West China Hospital of Sichuan University. Patients will be asked to stay awake and to keep their heads still during the scan, with their eyes closed and ears plugged. Scans will be performed with the following procedures: localizer, three-dimensional T1-weighted imaging (3D-T1WI), blood oxygenation level-dependent fMRI (BOLD-fMRI) and diffusion tensor imaging (DTI) sequence. The 3D-T1WI scanning parameters will be as follows: repetition time (TR)\u0026thinsp;=\u0026thinsp;6.008 ms, echo time (TE)\u0026thinsp;=\u0026thinsp;1.7 ms, data matrix\u0026thinsp;=\u0026thinsp;256 \u0026times; 256, field of view (FOV)\u0026thinsp;=\u0026thinsp;256 \u0026times; 256 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The BOLD-fMRI scanning parameters will be as follows: 31 contiguous slices with a slice thickness of 5 mm, TR\u0026thinsp;=\u0026thinsp;2000 ms, TE\u0026thinsp;=\u0026thinsp;30 ms,FOV\u0026thinsp;=\u0026thinsp;240 \u0026times; 240 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, Matrix\u0026thinsp;=\u0026thinsp;64 \u0026times; 64, flip angle (FA)\u0026thinsp;=\u0026thinsp;90\u0026deg;, total volumes\u0026thinsp;=\u0026thinsp;240. The DTI data will be acquired using a single-shot echo planar image sequence with the following parameters: FOV\u0026thinsp;=\u0026thinsp;256 \u0026times; 256 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, TR\u0026thinsp;=\u0026thinsp;8500 ms, matrix\u0026thinsp;=\u0026thinsp;128 \u0026times; 128, slice thickness\u0026thinsp;=\u0026thinsp;2 mm with no gap. Two diffusion-weighted sequences were acquired using gradient values b\u0026thinsp;=\u0026thinsp;1000 s/mm\u003csup\u003e2\u003c/sup\u003e and b\u0026thinsp;=\u0026thinsp;0 s/mm\u003csup\u003e2\u003c/sup\u003e with the diffusion-sensitizing gradients applied in 64 non-collinear directions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cdiv id=\"Sec16\" class=\"Section3\"\u003e\n\u003ch2\u003eClinical data analysis\u003c/h2\u003e\n\u003cp\u003eThe comprehensive effectiveness analysis will use the per protocol set (PPS) and the full analysis set (FAS). The FAS population will be used as the primary population for all efficacy analyses. The safety set (SS) included all subjects who received at least one treatment after randomization. When the results of PPS analysis and FAS analysis are inconsistent, PPS and FAS are discussed separately to find out the reasons for the inconsistency. Missing data will be handled using the last-observation-carried-forward (LOCF) method.\u003c/p\u003e\n\u003cp\u003eStatistical analysis will be conducted using SPSS 26.0 (IBM, Chicago, IL, USA) statistical software. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 (two-sided) is considered statistically significant. Quantitative data are described with mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Qualitative data are described with frequency and percentage (N, %). \u003cem\u003eStudent\u0026rsquo;s t-\u003c/em\u003etest and \u003cem\u003echi-square\u003c/em\u003e test will be used to compare the differences between groups at baseline. The primary outcome will be carried out with a paired samples \u003cem\u003et\u003c/em\u003e-test, and the secondary outcome will be compared at four timepoints using the repeated measures ANOVA. Clinical data on skewed distribution will be compared using a non-parametric test.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n\u003ch2\u003eMRI data analysis\u003c/h2\u003e\n\u003cp\u003eThe fMRI data preprocessing and comparison will be performed using SPM12 software (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.fil.ion.ucl.ac.uk/spm/\u003c/span\u003e\u003c/span\u003e) based on MATLAB 2018a (Mathworks, Inc., USA). The steps including: format conversion, slice timing correction, head motion correction, spatial standardization, linear trend removal, spatial smoothing, and band-pass filtering. After pre-processing, the amplitude of low frequency fluctuation and regional homogeneity will be calculated to reflect the local cerebral functional activity, and the seeds-based functional connection analysis will be performed to reflect the functional integration of the brain. ANOVA will be used for comparisons between the two groups, with multiple comparison corrections.\u003c/p\u003e\n\u003cp\u003eFurthermore, the \u003cem\u003ePearson\u003c/em\u003e correlation analysis will be conducted to assess the associations between the changes of fMRI and the improvement of clinical symptoms.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first randomized controlled study that is aimed at investigating the clinical efficacy and underlying mechanisms of different acupuncture prescriptions for NP. The results of this study are beneficial for the prescription selection of acupuncture for treating NP, and elucidates on the mechanisms of acupuncture for NP.\u003c/p\u003e\n\u003cdiv\u003e\n\u003ch2\u003eSelection of acupoint prescription\u003c/h2\u003e\n\u003cp\u003eMany clinical studies have been performed on acupuncture for NP, and its efficacy has been identified. In clinical practice, the combination of local and distal points is a basic principle of acupoint prescriptions, but the number of prescriptions and acupoints involved is enormous. Therefore, in this study, two different prescriptions will be selected to compare their efficacy and possible mechanisms. Neck tenderness point will be selected as the basic acupoint, which is the most commonly used local acupoint in NP\u0026rsquo; treatment. LU7 and LU5, located in the forearm, will be selected as distal points in Group A. HT4 and HT3, also located in the forearm, will be selected as distal points in Group B. All these distal points are reported to be effective in some clinical trials on acupuncture for treating NP.\u003csup\u003e30\u0026ndash;32\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003ch2\u003eThe combination of subjective and objective outcome measures\u003c/h2\u003e\n\u003cp\u003ePain is an unpleasant sensory and emotional perception that is associated with actual or underlying tissue pathology.\u003csup\u003e33\u003c/sup\u003e Human behavior, psychological and social factors play a crucial role in the long-term maintenance of pain.\u003csup\u003e34\u003c/sup\u003e Therefore, the multidimensional nature of pain requires that the measurement of NP should include both subjective outcomes and objective outcomes. In this study, subjective outcomes including VAS, NDI, SAS and SDS will be used to assess pain perception, dysfunction, and emotional state of the patients. Moreover, objective outcomes including tenderness threshold, musculoskeletal ultrasound and ROM will be used to evaluate the improvement of symptoms in NP patients. The combination of subjective and objective outcomes can be more complementary to assess the efficacy from multiple perspectives and reduce the occurrence of potential bias, so as to improve the quality of clinical evidence.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv\u003e\n\u003ch2\u003eApplication of neuroimaging technology\u003c/h2\u003e\n\u003cp\u003ePrevious neuroimaging studies have demonstrated that patients with NP present with abnormalities in brain activity and structure. For example, Chen et al.\u003csup\u003e35\u003c/sup\u003e found increased spontaneous brain activity in the supplementary motor area of NP patients, and subsequently suggested a correlation between abnormality of the salience network with the disease. Another single fMRI-based case control study associated NP with activation and/or recall of pain memory.\u003csup\u003e36\u003c/sup\u003e Elsewhere, a voxel-based morphometry study performed on NP patients revealed that the loss of bilateral clusters of gray matter in the sensorimotor cortex and pulvinar nucleus with NP pathophysiology.\u003csup\u003e37\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eMoreover, it has been reported that central integration is the key determinant of the effectiveness of acupuncture.\u003csup\u003e38\u003c/sup\u003e With previous studies, performed on individuals with shoulder pain,\u003csup\u003e39\u003c/sup\u003e fibromyalgia,\u003csup\u003e40\u003c/sup\u003e and low back pain,\u003csup\u003e41\u003c/sup\u003e as well as knee osteoarthritis\u003csup\u003e12\u003c/sup\u003e indicating that regulation of brain activity might be an important factor influencing acupuncture\u0026rsquo;s modulating effects on pain. For example, acupuncture has been shown to effectively reduce pain by modulating brain regions related to both sensory-discriminative and emotional aspects.\u003csup\u003e42\u003c/sup\u003e Such regions were found to be important for the therapeutic effects of acupuncture on NP.\u003csup\u003e35\u003c/sup\u003e Based on these evidences, we hypothesize that acupuncture can effectively treat NP by modulating alteration of brain activity.\u003c/p\u003e\n\u003cp\u003eThis trial is the first study to use fMRI to explore the potential central mechanisms of different acupuncture prescriptions for the treatment of NP. The results of this trial will help to provide visualization evidence for the clinical application of acupuncture for NP treatment.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Trial Status","content":"\u003cp\u003eThe trial is currently in the recruitment phase and the study is expected to end in December 2021.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e3D-T1WI Three-dimensional T1-weighted imaging\u003c/p\u003e\n\u003cp\u003eBOLD-fMRI Blood oxygenation level-dependent fMRI\u003c/p\u003e\n\u003cp\u003eRS-fMRI Resting state functional magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eCRF Case report form\u003c/p\u003e\n\u003cp\u003eDTI Diffusion tensor imaging\u003c/p\u003e\n\u003cp\u003eFA Flip angle\u003c/p\u003e\n\u003cp\u003eFAS Full analysis set\u003c/p\u003e\n\u003cp\u003eFDR False Discovery Rate\u003c/p\u003e\n\u003cp\u003eFOV Field of view\u003c/p\u003e\n\u003cp\u003eGLM General Linear Model\u003c/p\u003e\n\u003cp\u003eHbO Oxygenated hemoglobin\u003c/p\u003e\n\u003cp\u003eHbR Deoxygenated hemoglobin\u003c/p\u003e\n\u003cp\u003eLOCF Last observation carry-forward\u003c/p\u003e\n\u003cp\u003eMRI Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMSUS Musculoskeletal ultrasound\u003c/p\u003e\n\u003cp\u003eNDI Neck Disability Index\u003c/p\u003e\n\u003cp\u003eNP Neck Pain\u003c/p\u003e\n\u003cp\u003eNIH National Institutes of Health\u003c/p\u003e\n\u003cp\u003ePPS Per protocol set\u003c/p\u003e\n\u003cp\u003ePPT Pressure pain threshold\u003c/p\u003e\n\u003cp\u003eROM Range of motion\u003c/p\u003e\n\u003cp\u003eSD Standard Deviation\u003c/p\u003e\n\u003cp\u003eSF-36 Short-form 36-item Health Survey\u003c/p\u003e\n\u003cp\u003eSAS Self-Rating Anxiety Scale\u003c/p\u003e\n\u003cp\u003eSDS Self-Rating Depression\u003c/p\u003e\n\u003cp\u003eSS Safety set\u003c/p\u003e\n\u003cp\u003eTCM Traditional Chinese Medicine\u003c/p\u003e\n\u003cp\u003eTE Echo time\u003c/p\u003e\n\u003cp\u003eTR Repetition time\u003c/p\u003e\n\u003cp\u003eVAS Visual Analogue Scale\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial has been approved by the Institutional Review Boards and Ethics Committees of the First Teaching Hospital of CDUTCM (Approved number: 2020KL-007) and has been registered in the Chinese Clinical Trial Registry (ID: ChiCTR2000040930). Only patients who have signed the informed consent form will be included.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics and dissemination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval of this study has been approved by the Ethics Committee of the Hospital of Chengdu University of Traditional Chinese Medicine (No. 2020KL-007). The outcomes of the trial will be disseminated through peer-reviewed publications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study is financially supported by the National Key Research and Development Program in China (2018YFC1704606).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFZ and LJ are responsible for this study. FZ, LJ, ZG, TY, and LL conceived and designed the study. ZG, TY, and LL participated in drafting the trial protocol and preparing the manuscript. SR, LD, HG, JC, and HZ participated in data collection and were in charge of recruitment and treatment of patients. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Haifa Qiao and Gang Lu for the help of participants enrollment.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSafiri S, Kolahi AA, Hoy D, et al. Global, regional, and national burden of neck pain in the general population, 1990-2017: systematic analysis of the Global Burden of Disease Study 2017. \u003cem\u003eBMJ (Clinical research ed)\u003c/em\u003e 2020;368:m791. doi: 10.1136/bmj.m791 [published Online First: 2020/03/29]\u003c/li\u003e\n\u003cli\u003eCohen SP. 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Acupuncture Effect and Mechanism for Treating Pain in Patients With Parkinson's Disease. \u003cem\u003eFrontiers in neurology\u003c/em\u003e 2019;10:1114. doi: 10.3389/fneur.2019.01114 [published Online First: 2019/11/07]\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neck pain, Acupuncture, Central mechanism, Functional magnetic resonance imaging, Protocol","lastPublishedDoi":"10.21203/rs.3.rs-377610/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-377610/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAcupuncture is effective for reducing the symptoms of neck pain (NP). However, the underlying mechanisms are not fully elucidated. Based on evaluating the efficacy of two acupuncture prescriptions for treating NP. This study aims to investigate the potential central mechanism of acupuncture treatment for NP by functional magnetic resonance imaging (fMRI). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis is a randomized controlled trial, 86 patients will be randomly assigned into two acupuncture treatment groups at a ratio of 1:1. The whole study period includes 2 weeks baseline, 2 weeks treatments and 12 weeks follow-up (4 and 12 weeks after treatment). The pain severity, the neck disability index, the cervical range of motion, the pressure pain threshold, etc. will be used to evaluate clinical efficacy of two acupuncture prescriptions for NP treatment. The MRI scans will be performed to detect cerebral activity changes of 20 patients in each group. The clinical data and MRI data will be analysed, respectively. \u003cem\u003ePearson\u003c/em\u003e correlation coefficient will be used to evaluate the association between changes of cerebral activity features and improvement of clinical symptoms.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDiscussion: \u003c/strong\u003eThe results might provide further evidence for the clinical application of acupuncture in the treatment of NP.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: Chinese Clinical Trial Registry, ChiCTR2000040930. 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