Evaluation of the efficacy of catgut implantation at acupoint in the treatment of musculoskeletal pain: a protocol for systematic review and meta-analysis based on randomized controlled clinical trials

Abstract

Background and objectives:

Musculoskeletal pain is one of the most common conditions in the general population, causing a variety of adverse effects. In addition to pharmacological treatments, the use of acupuncture has increased in recent decades and has shown satisfactory effects. However, the effect of catgut implantation at acupoint (CIA), a specific form of acupuncture, on the treatment of musculoskeletal pain has remained uncertain. Therefore, the aim of this study is to access whether CIA is effective and safe compared with other treatments for musculoskeletal pain.

Methods:

Nine electronic databases, including six English databases (e.g. Medline and Embase) and three Chinese databases (e.g. CNKI and Wanfang database) will be searched from the inception to 1 May 2024. Only randomized controlled trials evaluating the effect of CIA for musculoskeletal pain in adults will be included. Two reviewers will independently perform the literature screening, data extraction and quality assessment. Primary outcome is pain symptoms assessed by any pain scale (e.g. visual analogue scale). Pooled results will be calculated using a fixed-effects model if heterogeneity is not significant (I² < 50%), otherwise, a random-effects model will be used. Several subgroup analyses and sensitivity analyses will be performed. All statistical analyses will be conducted using STATA 18.0.

Results:

A synthesis of the current evidence on the effect of CIA on the treatment of musculoskeletal pain will be published in a peer-reviewed journal.

Conclusions:

This study will provide high quality evidence of the effect of CIA on the treatment of musculoskeletal pain.

Introduction

Musculoskeletal pain is one of the most commonly reported medical condition^[1]. The prevalence of musculoskeletal pain in the general population ranges from 30% to 69.3%^[2,3]. Musculoskeletal pain can have a wide range of adverse effects, including loss of work productivity, limitations in daily activities, increased medical costs and reduced quality of life^[4]. The most commonly prescribed pharmacological agents for musculoskeletal pain are non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. However, long-term use of these drugs is not recommended because of significant side effects^[5], such as weight gain or loss, gastrointestinal symptoms, dizziness and even an increased risk of heart attack or stroke.

HIGHLIGHTS

• This study will provide comprehensive evidence of the effect of catgut implantation at acupoint (CIA) on the treatment of musculoskeletal pain.

• The results in this study will contribute to the popularization and application of CIA for the treatment of musculoskeletal pain.

In recent years, since fewer side effects, the interest in complementary and alternative medicine (CAM) therapies for musculoskeletal pain has increased^[6,7]. Among the various CAM therapies, acupuncture is one of the most widely used in the world. As an important part of Traditional Chinese Medicine (TCM), acupuncture has a long history of use in China, and has been shown to be effective for musculoskeletal pain such as shoulder impingement syndrome, acute lumbar sprain and chronic neck pain^[8]. However, the effects of catgut implantation at acupoint (CIA), a specific form of acupuncture^[9], on musculoskeletal pain have been less well studied, and the results of published studies were inconsistent^[10]. CIA involves the insertion of medical threads (e.g. catgut or polydioxanone) into subcutaneous tissue or muscle at specific points (e.g. traditional acupuncture points or tender points) to achieve a therapeutic effect^[11]. There are two components in CIA, a guide needle and the medical threads. The needle is removed after insertion and the medical threads remain embedded in the subcutaneous tissue or muscle. The embedded thread gradually softens, decomposes and dissolves with time in the subcutaneous tissue or muscle. Absorption of polydioxanone is known to be slow during the first 3 months and proceeds until 180–210 days^[12]. CIA has been widely used in Korea, China and Taiwan in recent years for the treatment of musculoskeletal pain^[13].

Several studies have reported that CIA can have a strong and long-lasting therapeutic effect compared with conventional acupuncture^[14-16]. For example, one randomized controlled trial (RCT) confirmed that CIA had a better effect than conventional acupuncture in reducing the short-term pain of patients with lumbar intervertebral disc herniation (reduction in visual analogue scale [VAS] score: −33.7 vs. −15.6, P = 0.01)^[16]. However, this result was not shown in several other trials^[14]. Given the conflicting results of published trials, we conducted this systematic review and meta-analysis to evaluate whether CIA is effective and safe compared with other treatments for musculoskeletal pain.

Methods

Study protocol and registration

This systematic review protocol has been registered on PROSPERO (registration number CRD42023476210) and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P)^[17]. Ethical approval is not necessary as this is a secondary research based on published data.

Criteria for considering studies for this review

Types of study

We will only include RCTs (parallel groups) that used well-described randomization methods to assess the effect of CIA for musculoskeletal pain in adults. Quasi-randomized controlled studies, observational studies, non-human studies, reviews, comments, case reports, letters, editorials, and duplicate publications will be excluded.

Types of participants

We will include patients of either sex, aged 18 and older with musculoskeletal pain. There will be no restrictions based on disease onset. However, we will exclude studies that include patients with pain due to headache and systemic disease.

Types of intervention and control

Intervention groups receive CIA treatment at specific points (e.g. traditional acupuncture points or tender points) and control groups receive no treatment, sham control or active treatment (e.g. conventional acupuncture, electroacupuncture, physical therapy, surgery or other traditional medical treatment). Studies in which the effects of CIA were compared with herbal medicine will be excluded.

Outcome measures

The primary outcomes are pain symptoms assessed using any pain scale, including VAS, numeric rating scale (NRS), neck pain and disability Scale (NPDS), and Japanese orthopaedic association scores (JOA)^[14,18-20]. The secondary outcomes are: (1) functional outcome measures (e.g. validated questionnaire or functional scale specific to the musculoskeletal disease, such as the range of motion [ROM]); (2) quality of life assessed using a validated scale (e.g. 36-item short-form, Euro-QoL); and (3) adverse events related to CIA.

Search methods for identification of studies

We will search nine electronic databases (six English databases and three Chinese databases) from their inception to 1 May 2024, including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, the China National Knowledge Infrastructure (CNKI), Weipu database, and Wanfang database. Both Medical Subject Headings (MeSH) and free text terms will be combined to identify relevant articles, The search terms consisted of two parts: “musculoskeletal pain, muscle pain, arthralgia, neck pain, shoulder pain, elbow pain, back pain, knee pain” and “catgut implantation at acupoint, embedding therapy, catgut embedment, needle embedding or thread implantation.” The specific search strategy for PubMed is shown in Table 1, which includes all search terms, and similar strategies will be adapted for other electronic databases. Reference lists of included studies and published reviews will be manually retrieved for additional potentially relevant studies.

Table 1.

PubMed search strategy.

Number	Search terms
#1	“catgut implantation at acupoint” [Title/Abstract]
#2	“embedding therapy” [Title/Abstract]
#3	“catgut embedment” [Title/Abstract]
#4	“needle embedding or thread implantation” [Title/Abstract]
#5	#1 OR #2 OR #3 OR #4
#6	“Musculoskeletal Pain”[Mesh]
#7	“Arthralgia”[Mesh]
#8	“Neck Pain”[Mesh]
#9	“Shoulder Pain”[Mesh]
#10	“Back Pain”[Mesh]
#11	“Low Back Pain”[Mesh]
#12	“muscle pain”[Title/Abstract]
#13	“elbow pain”[Title/Abstract]
#14	“knee pain”[Title/Abstract]
#15	#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14
#16	#5 AND #15
#17	#16 Filters: Randomized Controlled Trial

Study selection

According to the above inclusion criteria, two authors will independently screen the title, abstract, and full text by using Endnote (version X9). Any disagreement will be resolved by negotiation through adjudication or arbitration by a third author. The flowchart of the selection process will be presented in the PRISMA flowchart (Fig. 1).

Figure 1.

The PRISMA flow chart of the studies selection process.

Data extraction

Two independent authors will use a standardized and pilot-tested form will to extract necessary data from each eligible study, including first author name, year of publication, country of origin, period of study conduct, sample size, age of the participants, type of intervention and control, outcome, the means of outcome measures, number of participants randomized, number of participants analyzed, pain scale scores or number of positive events in the treatment and control groups, and effect estimates (e.g. relative risk [RR], hazard ratio [HR], adjusted odds ratio [OR], and corresponding 95% CIs). Any disagreements will be resolved by discussion. If data from the same study were reported in more than one report, we will select the report with the largest sample size.

Assessing risk of bias in included studies

Two authors will independently assess the risk of bias for each included study using the Cochrane Collaboration’s risk of bias tool^[21]. The critical assessment for the risk of bias will be assessed in seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessors, incomplete outcome data, selective reporting and other sources of bias. The risk of bias for each domain will be rated as “low risk,” “unclear risk” or “high risk.”

Measures of treatment effect

Mean difference (MD) or standardized mean difference (SMD) will be used to assess the treatment effect with 95% CIs for continuous data (e.g. VAS scores or NRS scores). SMD will be used when the same outcome variable is measured using different scales. RR or HR with 95% CIs will be used to assess the treatment effect for dichotomous outcomes (e.g. responder or non-responder).

Dealing with missing data

When there are insufficient data or missing data, the corresponding author will be contacted to request additional information or clarification. If the corresponding author cannot be contacted, the available data alone will be analyzed.

Data synthesis

The I² statistic and Cochran’s Q test will be used to test for heterogeneity between the studies. The fixed-effect model will be used if I² ≤ 50%, otherwise the random-effect model will be used. Publication bias will be assessed using funnel plots, Begg’s test, and Egger’s test. When testing for publication bias, P< 0.05 will be considered statistically significant. Three subgroup analyses will be performed: (1) different disease that (e.g. low back pain vs. knee osteoarthritis pain); (2) study conducted in different country (e.g. China vs. not China); (3) different control group treatments (conventional acupuncture vs. other treatments). We will conduct three sensitivity analyses to test the robustness of the primary pooled results: (1) removing the included studies one at a time; (2) omitting studies with high risk of bias; (3) using trim and fill adjusted analysis to test the influence of potential for publication bias.

Discussion

As a specific form and modern development of conventional acupuncture, CIA has attracted the attention of both Traditional Chinese Medicine and modern medicine due to the strong and long-lasting therapeutic effect^[14,15]. CIA has shown good clinical effect for many diseases, such as herniated intervertebral disc of the lumbar spine, chronic low back pain, shoulder-hand syndrome, knee osteoarthritis^{[14,15,22,23]} However, the effect of CIA for musculoskeletal pain treatment was uncertain. This study, which will provide high quality evidence, will contribute to the popularization and application of CIA for the treatment of musculoskeletal pain.

Our study has two main strengths. First, this study will comprehensively evaluate the effects of CIA treatments for musculoskeletal pain by including studies both in English and Chinese databases. As China is one of the regions with the most extensive clinical use of CIA, only by including all relevant studies conducted in China are included can we provide comprehensive evidence. Second, in our analysis, we will use multiple subgroup analyses and sensitivity analyses to further validate the reliability of the results.

Ethical approval

Not applicable.

Consent

Not applicable.

Sources of funding

Project of Traditional Chinese Medicine Bureau of Guangdong Province (20241005); Natural Science Foundation of Guangdong Province (Grant No. 2022A1515011260). All foundations had no influence on the development of the protocol.

Author contributions

The original idea of this research was conceived by C.J.W.; X.H.L. designed the protocol and drafted the manuscript; Y.J.H., Y.T.L., and Y.Q.C. participated in developing the eligibility criteria, search strategy, and data extraction methods; XHL registered the protocol in the International Prospective Register for Systematic Reviews and Meta-analysis.

Conflicts of interest disclosure

None.

Research registration unique identifying number (UIN)

This systematic review protocol has been registered on PROSPERO (registration number CRD42023476210).

Guarantor

Changjun Wang.

Provenance and peer review

This paper was not invited.

Data availability statement

Not applicable.

Assistance with the study

None.