Three Acupuncture Methods for Postoperative Pain in Mixed Hemorrhoids: A Systematic Review and Network Meta-Analysis

Background Mixed hemorrhoids are a common anorectal disorder, surgery is the most effective means of eradicating hemorrhoids, and pain is the most common postoperative complication of mixed hemorrhoids. Objective To compare the clinical efficacy of auricular plaster, acupoint application, and acupoint catgut embedding for treating postoperative pain in mixed hemorrhoids. Method PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched for randomized controlled trials (RCTs) of three acupuncture-related therapies for postoperative pain in mixed hemorrhoids from the time of database creation to October 2021. After screening the literature, extracting information, and evaluating the risk of bias of included studies, statistical analysis was performed using RevMan 5.3 and Stata 15.0. Result Forty-seven RCTs with a total of 5121 patients were included. Network meta-analysis (NMA) showed that auricular plaster (OR = 5.90, 95% CI = (2.02, 17.21)) and acupoint catgut embedding therapy (OR = 5.55, 95% CI = (1.01, 30.40)) were more effective than analgesics in the treatment of postoperative pain in mixed hemorrhoids. The cumulative ranking probability (SUCRA) showed that acupoint application (73.6%) had the best overall efficacy and the rest were auricular plaster (68.7%), acupoint catgut embedding therapy (64.6%), auricular plaster combined with acupoint application (63.4%), and pain medication (8.9%) in that order. Secondly, auricular plaster (OR = −0.93, 95% CI = (−1.66, −0.20)), acupoint catgut embedding (OR = −0.8, 95% CI = (−1.50, −0.10)), and acupoint application (OR = −1.4, 95% CI = (−2.50, −0.31)) all led to a significant decrease in pain scores and were all more effective than analgesics. As ranked by SUCRA, the results showed that the efficacy of acupoint application (73.5%) was optimal and the rest were auricular plaster (56.1%), acupoint catgut embedding (50.2%), and pain medication (15.3%) in that order. In terms of pain degree, acupoint application (OR = 3.83, 95% CI = (1.25, 11.74)) was significantly better than pain medication. Conclusion Acupoint application can improve the overall efficiency, reduce pain scores, and relieve the degree of postoperative pain in mixed hemorrhoids.


Introduction
Mixed hemorrhoids are a common anorectal disease [1], surgery is the most effective means of eradicating hemorrhoids [2], and pain is the most frequent postoperative complication of mixed hemorrhoids. Postoperative pain in hemorrhoids is a thorny problem that has troubled patients and physicians for a long time; it makes patients extremely nervous psychologically and fearful of defecation after sur-gery, which seriously affects the quality of surgery [3]. Pain arises for various reasons: (1) the innervation of the spinal nerve below the dentate line makes the pain response sensitive, (2) there is release of inflammatory mediators after surgery, and (3) there is postoperative stimulation of the wound surface by activities such as defecation and dressing changes, resulting in persistent spasm of the sphincter muscle [4].
In clinical practice, drug therapy is mostly used for postoperative pain in hemorrhoids but it requires multiple doses within a short period of time, which easily causes adverse reactions in the gastrointestinal tract and central nervous system, often resulting in dizziness, nausea, vomiting, dry mouth, and itchy skin [5][6][7], and the high cost of drugs increases the economic burden of patients. Therefore, the basic principle of pain management is to effectively relieve pain while minimizing the adverse effects of drugs and the cost of treatment. This has led to an urgent clinical need for nonpharmacological approaches to alleviate patients' pain and improve their quality of life.
Acupuncture is an important part of Traditional Chinese medicine, and acupuncture mainly includes auricular plaster, acupoint application, and acupoint catgut embedding, compared with conventional acupuncture, which is simple to operate, saves consumables and time cost, and can avoid the pain caused by applying regular acupuncture to patients. However, there is a lack of comparative studies on the efficacy of the three treatment methods and it is difficult to obtain a clear comparison by traditional meta-analysis. In this study, NMA was used to screen the best therapeutic measures based on ranking efficacy indexes for postoperative pain in hemorrhoid treatment in acupuncture to provide a reliable evidence-based reference for the clinic.

Methods and Analysis
2.1. Search Strategy. PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched from the establishment to October 2021 to find clinical randomized controlled trials about 3 acupuncture therapies, auricular plaster, acupoint application, and acupoint catgut embedding, for the postoperation pain of mixed hemorrhoids. PubMed was used as an example, and a combination of subject terms and free words were used for the search. The search strategy is shown in Table 1.            . Based on the inclusion and exclusion criteria, two independent researchers conducted a detailed screening of titles and abstracts of reference records identified through database searching. All potential articles that meet the eligibil-ity criteria and controversial literature were required for a fulltext review. The third researcher will conduct the arbitration, who was responsible for resolving the conflict between the two researchers. A total of 924 relevant papers were obtained from the initial review, and 47 RCT studies were finally included after the stratified screening ( Figure 1).

Quality Evaluation. Two investigators assessed the quality of the included studies according to the Cochrane Risk of Bias
Assessment Tool recommended in the Cochrane Systematic Assessment Manual, version 5.1. The Cochrane Risk of Bias Assessment included seven aspects: randomization methods, blinding of participants and investigators, blinding of evaluators, allocation concealment, completeness of outcomes, selective reporting of outcomes, and other sources of bias. Bias was assessed for each of the included RCTs in terms of low risk, high risk, and unclear [8]. Any inconsistency was resolved through joint discussions with third-party investigators.    2.5. Statistical Analysis. The risk bias was evaluated using RevMan 5.3 software. The included literature was compared directly using Stata 15.0 software, I 2 ≤ 50%, P ≥ 0:05 was considered as no statistical heterogeneity in the included literature, and the meta-analysis was performed using the fixed-effect model; I 2 > 50% or P < 0:05, the included literature was statistically heterogeneous, and a random-effects model was used for meta-analysis.

Data Information
The ranking between interventions was obtained by direct and indirect comparisons using Stata 15.0 software, with odd ratios (OR) for dichotomous variables and standardized mean difference (SMD) and 95% credible intervals (CI) for continuous variables. The closed loop formed by studies with both direct and indirect evidence was performed to test inconsistency, the surface under the cumulative ranking curves (SUCRA) closer to 100%, the better the efficacy of the intervention, and the difference is considered statistically significant at P < 0:05.

Publication Bias Analysis and Small Sample Effect Assessment
Because 34 of the 47 publications reported pain scores, this study used pain scores as an outcome indicator to test for small sample effects or publication bias and the funnel plot showed that most of the study scatters were located between the funnel plot and were more symmetrical, suggesting that there may be a small publication bias ( Figure 14).

Discussion
This study is aimed at discussing the efficacy of three different acupuncture therapies (auricular plaster, acupoint application, and acupoint catgut embedding) for postoperative pain in mixed hemorrhoids. 47 RCTs involving 5121 patients were included in this study. The results of the NMA showed that auricular plaster, acupoint application, and acupoint catgut embedding were superior to pain medication and conventional treatment in improving the overall efficiency and the ranking results showed that acupoint application was the most effective. Reducing postoperative pain scores, auricular plaster, acupoint application, and acupoint catgut embedding were superior to pain medication and conventional treatment. Auricular plaster combined with acupoint application was probably the most effective, followed by acupoint application. However, of the 47 studies included in this study, only 3 [19,32,46] had auricular plaster combined with acupoint application, which is a small sample size, and more studies need to be included to confirm the efficacy of the combined therapy. In terms of reducing postoperative complications, auricular plaster, acupoint application, and acupoint catgut embedding were superior to pain medication and conven-tional treatment and acupoint application was the most effective, significantly reducing postoperative edema, urinary retention, and other complications; in terms of safety, auricular plaster, acupoint application, and acupoint catgut embedding were superior to pain medication. Acupoint catgut embedding was the most effective for the onset of effect of the three acupuncture interventions; it was found that the analgesic effect was superior to that of analgesics at different time periods of 24 h, 48 h, and 72 h postoperatively. The perianal area is a concentrated area of nerve endings and is more sensitive to nociception. As the effects of anesthesia wear off, patients have a painful process that lasts 24 h to 48 h [55]. This study found that it still has a better analgesic effect at 72 h postoperatively, indicating that the effect of acupuncture for postoperative pain on mixed hemorrhoids is long lasting and stable, guiding that the treatment course of the three acupuncture therapies for postoperative pain in mixed hemorrhoids should last at least until 72 h for better therapeutic effect.
Nowadays, medical treatment of postoperative pain in mixed hemorrhoids mostly uses opioid analgesics, nonsteroidal anti-inflammatory drugs, central analgesics, etc. Although the pain relief effect is good, drug side effects such as nausea, dizziness, vomiting, and sweating can easily occur [56,57], with adverse reactions as high as 37% [58]. Acupuncture therapy, as a green complementary alternative therapy, has better clinical efficacy for postoperative pain in mixed hemorrhoids.
This study showed that the efficacy of acupoint application for postoperative pain in mixed hemorrhoids was more advantageous compared with other therapies. In fact, the mechanism of acupoint application for postoperative pain in mixed hemorrhoids is more widely studied, which may be related to its good efficacy. Acupoint application is based on the guidance of Chinese medicine meridian science, and the drug is applied to specific points on the body surface, both for acupuncture point stimulation and for absorbing the active ingredients of the drug through the skin tissue, producing a local concentration of the drug and playing  This study showed that the efficacy of acupoint application for postoperative pain in mixed hemorrhoids was more advantageous compared with other therapies. In fact, the mechanism of acupoint application for postoperative pain      in mixed hemorrhoids is more widely studied, which may be related to its good efficacy. Acupoint application is based on the guidance of Chinese medicine meridian science. The drug is applied to specific points on the body surface, both for acupuncture point stimulation and for absorbing the active ingredients of the drug through the skin tissue, producing a local concentration of the drug and playing the dual role of Chinese medicine and meridian regulation at the same time. Medical research has shown that transacupoint-applied drugs have permeability, exosensitivity, and amplification effects [47]. Another study showed that acupoint application could produce the effect of biological function through biological wave meridian points, through the process of absorption, transmission, and reflection, to activate blood and remove blood stasis, unblock meridians, and achieve pain relief [59]. The local absorption of drugs in the skin reduces the adverse reactions in the gastrointestinal tract [60]. In modern medicine, acupoint application therapy is classified as TDS, the transdermal drug delivery system of Chinese medicine [61]. 90% of the human dermis is a vascular-rich connective tissue, and the drug is absorbed into the blood through keratin transit, and the keratin layer is the main barrier for transdermal absorption, which forms a dense state locally after acupoint application, causing the cells of the keratin layer to swell into a porous state and make its tight structure lose, letting it easy for the drug to penetrate [62].
As a part of Chinese traditional medicine, acupuncture therapy has the advantages of precise efficacy, low toxic side effects, and easy acceptance by patients. In recent years, acupuncture therapy has gradually become the mainstream of global medicine as a green alternative or complementary treatment [63,64]. Compared with conventional drug therapy, it can effectively reduce drug side effects and postoperative complications such as urinary retention and traumatic edema, as well as reduce the economic burden of patients [65,66], and even if it cannot completely replace analgesics, it can participate in the synergistic use of drugs and reduce

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Computational and Mathematical Methods in Medicine the number and dose of analgesic drugs taken by patients, thus reducing the occurrence of adverse reactions in patients. Compared to ordinary acupuncture, the three acupuncture treatments avoid the pain caused to patients by multiple needle sticks, reduce the workload of medical personnel, and make up for the short duration of the curative effect of ordinary acupuncture and the large arbitrariness of the operation. More importantly, there is no need to change the needles daily, which helps improve patient compliance and promote the clinical grassroot application.
This study still has shortcomings, such as the lack of systematic and standardized methods for making homemade acupoint-applied plasters and the need to further standardize the methods for making acupoint-applied plasters. The methodological quality of the included studies was low, most of the studies did not mention the distribution concealment method, and due to the specificity of acupuncture therapy, most of the studies were not implemented blinded, which may produce implementation bias; in order to reduce bias and make the results more reliable, in the future, researchers should follow the CONSORT reporting standards [67]. The control group has drug interventions which did not consider the drug dose and duration and frequency, and the specific content of the acupuncture protocol was not explored, such as TCM identification, treatment frequency, and duration; the details of acupuncture therapy were reported unclear, which to some extent caused the bias of the study results and decreased the guiding effect on TCM clinical practice, and in future studies, clinical trials of acupuncture therapy should follow STRICTA standards [68]. For combination therapy, there are fewer clinical research trials, which can be a focus of future research to provide more possibilities for the selection of analgesic methods and provide evidence-based medical evidence reference for the use of this method in clinical practice. In a word, given the very low methodological quality of the included systematic evalua-tions and the risk bias of poor reporting of randomized controlled trials, a more rigorous design and standardized reporting are needed in the future to demonstrate the reliability of this study further.

Conclusion
Current evidence suggests that acupoint application therapy for the treatment of postoperative pain in mixed hemorrhoids has better efficacy in improving overall effectiveness and reducing pain scores as well as relieving pain levels.

Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Care Commission Scientific Research Project: clinical standardization study on the treatment of mixed hemorrhoids