Study design

This is a multicentre, age-matched and sex-matched case–control study. The protocol was developed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.12 The study has been registered with ChiCTR at Current Controlled Trials (ChiCTR1800016220). A flowchart of the study design is shown in figure 1.

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Figure 1

Flowchart of the study design.

Ethics

This study was designed in accordance with the principles of the Declaration of Helsinki. The study protocol has been approved, and is registered on the primary registry in the WHO registry network (Chinese Clinical Trial Registry: no. ChiCTR1800016220). Signed consent will be obtained from each participant after they have been informed of the study procedures, possible risks and their right to withdraw from the study.

Patients and healthy participants (controls)

Exclusion criteria

Patients are ineligible if they: (1) have complicated neck or shoulder pain caused by cervical and intervertebral disc degeneration, such as other types of cervical spondylosis, shoulder periarthritis, rheumatic myofibrillar inflammation; (2) have history of neck fracture or surgery or cervical congenital abnormality; (3) have serious disease related to the heart, liver, kidney or hematopoietic system; (4) have difficulty answering questionnaires because of cognitive impairment; (5) have dermatopathological diseases; or (6) are pregnant, breastfeeding or planning a pregnancy during the study period.

Healthy participants are ineligible if they: (1) have serious disease related to the heart, liver, kidney or hematopoietic system; (2) have cervical congenital abnormality; (3) have difficulty answering the questionnaires because of cognitive impairment; (4) have dermatopathological diseases; or (5) are pregnant, breastfeeding or planning a pregnancy during the study period.

Recruitment strategies

We will recruit patients from the outpatient departments of Acupuncture and Moxibustion, and Orthopaedics in five clinical centres in China: Chengdu University of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Shaanxi University of Traditional Chinese Medicine, Shanxi University of Traditional Chinese Medicine and Guiyang College of Traditional Chinese Medicine. Healthy participants without NP or shoulder pain will comprise age-matched and sex-matched residents from the same communities as the patients, to act as controls. Recruitment strategies will include posting advertisements on social media (such as WeChat, which is similar to Facebook) and at community centres, or by word-of-mouth introductions through participants already enrolled in the study. Patients or healthy participants who consent to study participation will be examined and diagnosed by a hospital doctor.

Test regions, acupoints and sensitised points

Following the results of literature data-mining and expert consensus on the treatment of NP, we identified the 15 most frequently used acupoints (table 1) and the five regions of the body with the most frequent occurrence of pain and the greatest degree of acupoint sensitisation. The body will be divided into five regions to standardise the treatment procedures and detection areas. Regions 1 and 2 are each bordered by the respective ipsilateral mastoid, sternal end of the clavicle, anterior axillary line, acromion and C7 spinous process. Region 3 is the triangular region bordered by both sides of the mastoid and the C7 spinous process. Regions 4 and 5 are each bordered by the respective ipsilateral C7 spinous process, acromion and axillary line; the two regions are divided by the posterior midline. These regions are the same as those used in previous studies of NP,13 and include the upper trapezius, splenius capitis muscles, sternocleidomastoid, levator scapulae, infraspinatus, scalene, subscapularis muscles and other neck muscles associated with NP.14 15 These regions and acupoints are shown in figure 2.

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Figure 2

The test regions and acupoints that will be used in the study.

Investigators will mark the 29 acupoints on each patient. All investigators will attend training to ensure all practices are standardised. Investigators will be blinded regarding whether participants are patients or healthy controls. The investigator will palpate the detection area associated with each acupoint using the appropriate force (<2000 gf), and will identify sensitised points that have pain/sourness/heaviness/fullness or nodules.

Outcome measurements

All data collection for each patient will be completed on the same day.

Body surface temperature

Thermal imaging technology has been widely used to assess pain and muscle damage.16 17 Each participant will be evaluated in a room with a constant temperature of 26°C. Investigators will use thermal imaging cameras (Fotric 226, IRS Systems, Allen, Texas, USA) to take measurements at each of the 29 acupoints in the five body regions. The temperature data for each point on the images will be analysed using professional software (AnalyzIR, IRS Systems, Allen, Texas, USA).

Mechanical pain threshold

Investigators will use the electronic Von Frey esthesiometer (model 2390; IITC Life Science, Woodland Hills, California, USA) to take two measurements of the mechanical pain threshold at each of the 29 acupoints in the five body regions in turn. Previous studies have found that this device can detect hyperalgesia and changes in sensory nerve function.18–20 Mechanical pain caused by punctate stimuli is related to Aδ-fibres.21 If there is a difference of more than 15 g between the two measurements of mechanical pain threshold made at one acupoint, the mechanical pain threshold at that acupoint will be measured a third time. Progressive pressure will be applied at a rate of 10 g/s at each acupoint, and we will calculate the average mechanical pain threshold for each acupoint. To reduce the consecutive assessment error for two adjacent points, an alternate assessment method for acupoints on the left and right sides of the body will be adopted.

Pressure pain threshold

The pressure pain threshold (PPT) is widely used clinically as a semiobjective method with which to quantify localised pain.22 23 Pain caused by blunt pressure stimuli is related to C-fibres.21 Investigators will use the FDIX Force Gauge (Force One FDIX, Wagner Instruments, Greenwich, Connecticut, USA) to take two PPT measurements at each of the 29 acupoints in the five body regions in turn. If there is a difference of more than 500 gf between the two PPT measurements performed at one acupoint, the PPT at that acupoint will be measured a third time. Progressive pressure will be applied at a rate of 100 gf/s at each acupoint, and the average PPT will be calculated. An alternate assessment method for the acupoints on the left and right sides of the body will be adopted.

Skin resistance

Investigators will use the Acupoint Dynamics Research Instrument (LMR30-RIII, Peking University, Beijing, China) to record the skin resistance at nine acupoints, bilateral (GB-21, GB-20, BL-11, LI-10, SI-3) and at the two most sensitive points (if there are two sensitive points).

Pain

NP will be measured using the Visual Analogue Scale, the Northwick Park Neck Pain Questionnaire and the McGill Pain Questionnaire. The visual analogue scale will be used to measure pain severity . The Northwick Park Neck Pain Questionnaire provides a reliable outcome measure for patients with NP, and the McGill Pain Questionnaire is used to measure the different qualities of subjective pain; these questionnaires have been proven valid, and are convenient for patients to complete.24 25

Neck function

Changes in neck function will be evaluated by measuring cervical range of motion.

General demographic information

This will include the collection of data regarding age, disease duration, medical history and medication type and dosage.

Safety and adverse events

Non-invasive assessments of the body surface do not generally cause adverse events. However, we will record the number and type (eg, serious pain, fainting) of adverse events in each group. Participants who experience adverse events will receive the appropriate intervention. We will report adverse events immediately to the primary investigator and the ethics committee, and the affected participants will be withdrawn from the study.

Patients and public involvement

Patients and the public have not and will not be involved in the design and conception of this study.

Sample size calculation

A previous study indicated that the rate of acupoint sensitisation in patients ranged from 20% to 70%26; therefore, we set this rate at 50% to calculate the minimum sample size required for the proposed study. With an acupoint sensitisation rate of 20% in healthy participants, the OR is 4. According to Chow’s formula for comparing two sample proportions,27 we assumed α=0.05, and β=0.01; thus, the smallest sample size is 408 with two-sided confidence and a ratio of control participants to cases of 1 (TrialSize package in R; The R Project for Statistical Computing, Copenhagen, Denmark). Setting the potential non-response rate and sampling effectiveness at 10%, the final sample size is 448 (224 patients, plus 224 age-matched and sex-matched healthy controls).

Statistical analysis

Data will be blinded, double-entered in EpiData V.3.1 software (EpiData Association, Odense, Denmark), and adequately checked for errors. SPSS V21.0 (IBM Inc, Armonk, New York, USA) will then be used to complete the statistical analyses. The statistical data evaluation will be performed independently by the West China School of Public Health at Sichuan University, China. Missing data will be processed without imputation. First, the distribution of basic information in the case and control groups will be described for age, sex, height, weight, occupation and education level. Data will be presented as means (SD) for continuous variables, and as frequency (percentage) for categorical variables. The distributions of sensitised points will be shown in scatter plots to represent skin morphological changes. We will also describe the distributions of the intensity of NP and neck function. Hypothetical testing will then be performed to assess the differences between the case and control groups regarding body surface sensations and biophysical properties, including body surface temperature, mechanical pain threshold, PPT and skin resistance. Parametric statistical testing (t-test) will be used for data that are normally distributed; otherwise, non-parametric statistical testing (Wilcoxon’s signed rank test) will be used. If there is a difference between the case and control groups in body surface temperature, mechanical pain threshold, PPT or skin resistance, the cut-off values for these indices to distinguish between sensitive and non-sensitive states (including heat sensitivity, pain sensitivity and electrical sensitivity) will be detected using receiver operating characteristic curve analyses. Finally, the acupoint sensitisation rates of the patients and healthy controls will be calculated separately for heat, pain and electrical sensitivity to identify the most important form of sensitivity for all acupoints. The OR will represent the ratio of acupoint sensitisation in the patients and healthy controls; therefore, we will combine OR and the sensitisation rate of all acupoints to determine the optimal points for each sensitisation.

Quality control

This is a multicentre observational study; therefore, quality control will play a vital role in extrapolating the conclusions. To ensure the integrity of the study and to protect the rights and health of the participants, we will set up a Data and Safety Monitoring Board. The Data and Safety Monitoring Board will be developed in accordance with the Operational Guidelines for the Establishment and Functioning of the Data and Safety Monitoring Boards of the WHO. Separate from the Data and Safety Monitoring Board, a quality control group will be established to guarantee the validity and reliability of results. Before study commencement, fieldwork operation manuals will be prepared, and pilot study participants from all centres will undergo training in accordance with the standard operating procedure of this study. Every 3 months, members of the quality control group will perform a quality control review at each study site and produce a report regarding the quality analysis of the entire data collection process.