Acupuncture Combined with Herbal Cake-Separated Moxibustion for Chronic Pelvic Pain in Sequelae of Pelvic Inflammatory Disease: Study Protocol for a Randomized Controlled Trial

Sequelae of pelvic inflammatory disease (SPID) refers to a series of long-term pathological changes and clinical manifestations resulting from delayed, inadequate, or incomplete treatment of pelvic inflammatory disease in women, leading to persistent or recurrent inflammation. 1 Chronic pelvic pain (CPP) is one of the most prevalent sequlae, characterized by non-cyclical pelvic pain lasting more than 6 months. This pain is typically localized to the lower abdomen and lumbosacral region and is often described as a sensation of heaviness, soreness, or dull ache. It is frequently exacerbated by physical exertion, sexual intercourse, and perimenstrual periods, significantly diminishing patients’ quality of life. 2–5 Currently, first-line treatment for CPP secondary to SPID predominantly comprises symptomatic interventions, including nonsteroidal anti-inflammatory drug (NSAID) analgesia, hormonal regulation, pelvic floor muscle training, and physical therapy. Standardized antibiotic use is recommended during acute exacerbations but are not routinely recommended in the chronic phase. For refractory pain, invasive treatments such as laparoscopic adhesiolysis and nerve blocks may be employed. 6–9 However, long-term use of NSAIDs may lead to adverse effects such as gastrointestinal discomfort and hepatorenal impairment. Hormonal therapy has certain contraindications and poor long-term efficacy, while invasive treatments involve significant trauma and high costs. Moreover, none of these therapeutic approaches can fundamentally improve the histopathological state of pelvic tissues, resulting in disease recurrence and high relapse rates, which fail to meet clinical treatment demands. 10 , 11 Acupuncture is a commonly used method in traditional Chinese medicine (TCM) clinical practice for the treatment of CPP. 12 , 13 In 2021, a large-sample randomized controlled clinical trial suggested that 20 acupuncture sessions within 8 weeks could significantly improve clinical symptoms of moderate-to-severe CPP, with therapeutic effects maintained for 24 weeks post-treatment. 14 Moxibustion exhibits therapeutic effects of warming meridians to dispel cold, promoting blood circulation to resolve stasis, and unblocking collaterals to relieve pain, thereby mitigating inflammatory responses and improving pelvic tissue adhesions. Relevant meta-analyses indicate that moxibustion-based therapies for SPID show significantly higher efficacy rates and pain relief outcomes compared to pharmacological treatments, with no significant differences in adverse reaction incidence. 15 , 16 However, contemporary investigations suffer from a paucity of robust clinical evidence. Presently, no clinical guidelines, such as those promulgated by the European Association of Urology (EAU), the Society of Obstetricians and Gynaecologists of Canada (SOGC), and the American College of Obstetricians and Gynecologists (ACOG), advocate for the adoption of this therapeutic approach. Additionally, the efficacy differences between acupuncture and acupuncture combined with moxibustion in treating CPP require further investigation. Based on this, this study adopted a randomized controlled trial design, using acupuncture as the control group to compare the clinical efficacy of acupuncture combined with herbal cake‑separated moxibustion in treating CPP caused by SPID. We selected the Visual Analogue Scale (VAS) as the primary outcome, given its precision and sensitivity in assessing patients’ pain symptoms. Additionally, the TCM Symptom Grading and Quantifying Standard Score was employed to reflect the efficacy of acupuncture from a traditional Chinese medicine perspective. This study aims to preliminarily explore the safety and effectiveness of acupuncture combined with herbal patch moxibustion for the treatment of CPP.

This is a single-center, double-arm, randomized controlled clinical trial, which will recruit patients at the Hospital of Acupuncture and Moxibustion of China Academy of Chinese Medical Sciences ( Figure 1 ). The trial has completed ethical review (Approval Number: S2023-06-29-3, Attachment 1 of the supplementary materials ) and trial registration (URL: https://itmctr.ccebtcm.org.cn , ITMCTR2026000339). Figure 1 Trial flow. Flowchart detailing a clinical trial process for CPP patients. The process begins with enrollment, followed by screening and informed consent. Randomization takes place in week 0, dividing patients into the experiment group and the control group, each with 43 participants. The experiment group undergoes treatment for 4 weeks, from week 1 to week 8, while assessments occur at week 4 and week 8 for the control group. Follow-up for both groups lasts 4 weeks, from week 9 - week 12, with an assessment at week 12. The process concludes with statistical analysis. Flowchart of a clinical trial process for CPP patients, including enrollment, allocation, follow-up and analysis. Trial flow. Patients will be recruited primarily through regular outpatient visits, posts on our hospital’s social media pages, and advertisements on WeChat. All patients must sign and complete an informed consent form ( Attachment 2 of the supplementary materials ) prior to randomization. The diagnostic criteria for pelvic inflammatory disease were formulated with reference to the “2021 Guidelines for the Treatment of Sexually Transmitted Diseases” of the Centers for Disease Control and Prevention (CDC) of the United States, 17 the “Chronic Pelvic Inflammatory Disease”, 18 section in Obstetrics and Gynecology, and the 2017 European Guidelines for the Management of Pelvic Inflammatory Diseases. 19 ( Table S1 in Attachment 3 of the supplementary materials ). Participants must meet all of the following criteria to be enrolled in the study: (1) Meet the diagnostic criteria of SPID; (2) Be female, aged between 22 and 50 years; (3) Present with chronic pelvic pain, defined as a mean VAS score of ≥ 4 points over the past week; (4) Voluntarily agree to participate and provide signed written informed consent prior to any study-related procedures. Patients will be excluded from participation if they meet any of the following conditions: (1) Present with symptoms related to other conditions such as ectopic pregnancy, ovarian cyst torsion/rupture, endometriosis, adenomyosis, pelvic venous congestion, or tuberculous pelvic inflammatory disease; (2) Acute exacerbation of pelvic inflammatory disease; (3) Patients who have received acupuncture, moxibustion, or any integrative Chinese and Western medicine therapies specifically for the management of for pelvic inflammatory disease within the past 1 month; (4) Present with concurrent severe cardiovascular or cerebrovascular diseases, hepatic or renal malignancies, hematologic malignancies, or psychiatric disorders. All participants will receive acupuncture treatment performed by licensed acupuncturists with at least 2 years of clinical experience, who underwent standardized training in the study protocol prior to trial initiation to ensure uniformity of needling techniques across both groups. The acupuncture protocol involves alternating between two sets of acupoint combinations. Set A (abdominal acupoints): Shuidao (ST28), Guilai (ST29), and Zhongji (CV3); and Set B (dorsal acupoints): a dorsal group comprising Shenshu (BL23), Zhongliao (BL33), and Huiyang (BL35). These two sets will be used on alternating treatment sessions ( Table S2 in Attachment 3 of the supplementary materials ). Routine skin disinfection will be performed at the acupoints. Disposable sterile acupuncture needles (0.25mm × 40mm or 0.30mm × 75mm, Hwato, Suzhou, China) will be used. Manual manipulations, including twirling and lifting-thrusting, are applied by the acupuncturist until the deqi response (a feeling of soreness, numbness, distension, or heaviness) is obtained. 20 The needles are then left in place for 20 minutes. Acupuncture treatment will be conducted three times per week, with each session separated by an interval of 1 to 2 days, over a total of 8 consecutive weeks. Follow-up will be conducted for 4 weeks after acupuncture treatment completion ( Table 1 ). Table 1 Acupoint Location and Manipulation Sequence Number Acupoint Manipulation 1 Shuidao (ST28) Insert obliquely toward the perineum at a depth of 4–5 cm 2 Guilai (ST29) Insert obliquely toward the perineum at a depth of 4–5 cm 3 Zhongji (CV3) Make a downward diagonal cut of 4–5 cm 4 Shenshu (BL23) Direct puncture 2.5–3 cm 5 Zhongliao (BL33) At a position approximately 0.5–1 cm superior and lateral to the third sacral posterior foramen, perform an inward and downward oblique puncture; once the practitioner feels a breakthrough sensation, advance the needle further by about 6–7 mm. 6 Huiyang (BL35) At the lateral border of the coccygeal end, insert a diagonal needle 6–7 mm outward and upward. Acupoint Location and Manipulation Acupuncture combined with herbal cake-separated moxibustion will be administered exclusively to patients in the experimental group. Herbal cake-separated moxibustion is a type of indirect moxibustion. In practice, a herbal cake prepared from pulverized Chinese medicinals (often blended with yellow wine or other excipients) is first placed on the target acupoint. A moxa cone (made of mugwort wool) is then positioned atop the cake and ignited. The radiant heat and mild thermal stimulus produced by the burning moxa penetrate through the herbal cake to reach the underlying acupoint. This intervention combines the thermotherapeutic effect of moxibustion, the percutaneous absorption of bioactive compounds from the herbal cake, and the specific regulatory actions of acupoint stimulation, with all three mechanisms acting in concert to produce the therapeutic outcome. In this study, the herbal cake-separated moxibustion is performed by trained nurses in a dedicated moxibustion room. The following medicinal materials are mixed in a weight ratio of 2:2:1:1:1. Aconiti Lateralis Radix Praeparata (Fuzi), Cornu Cervi Degelatinatum (Lurongshuang), Cinnamomi Cortex (Rougui), Olibanum (Ruxiang), and Testudinis Plastrum (Guiban), ground into powder using a grinder, and then mixed with yellow wine to make cakes 3 cm in diameter and 0.5 cm in height. Moxa cones are prepared from fine Artemisia wool, each formed into a conical shape measuring 2.5 cm in base diameter, 2 cm in height, and weighing about 2.5 g ( Figure 2 ). In this study, Shenque (CV8), Guilai (ST29) and Zhongji (CV3) in Set A, and Shenshu (BL23) and Zhongliao (BL33) in Set B are alternately selected for herbal cake-separated moxibustion. When acupuncture is applied to the abdominal points (Set A), herbal cake-separated moxibustion is subsequently performed on the dorsal points (BL23 and BL33); conversely, when needling the dorsal points (Set B), the moxibustion is applied to the abdominal points (CV 8, ST29 and CV3) after acupuncture. During the moxibustion procedure, if the patient experiences excessive local burning sensation, one or two layers of medical gauze may be placed under the herbal cake to prevent skin burns. Each moxa cone burns for approximately 15 minutes; after the cone has burned out and the local warm sensation subsides, the next cone is applied. Two cones are administered per acupoint per session. Moxibustion is applied until the local skin exhibits mild and even erythema, with an acceptable localized warmth, ensuring the absence of blisters, skin erosion, or intense burning pain. The treatment is given once every other day, three times per week, for 8 consecutive weeks, totaling 24 sessions. Figure 2 Schematic diagram of herbal cake separated moxibustion. ( A ): Front view of the herbal cake; ( B ): Side view of the herbal cake; ( C ): Herbal cake-separated moxibustion. Schematic of herbal cake-separated moxibustion: front view, side view and moxa cone setup. Schematic diagram of herbal cake separated moxibustion. ( A ): Front view of the herbal cake; ( B ): Side view of the herbal cake; ( C ): Herbal cake-separated moxibustion. During the trial period, the use of therapeutic agents for SPID and CPP is prohibited. Should any such medication be administered, the details (including drug name, dosage, route, and duration) must be recorded in the CRF. The primary outcome is the VAS score for CPP at week 8. The VAS 21 is a classic tool in the field of subjective sensation quantification, recognized as one of the “gold standards” for pain and other subjective symptom assessment due to its continuous measurement, high resolution, and ease of use. In this study, a 10-point VAS will be employed. A score of 0 indicates complete absence of pain and any discomfort; a score of 10 represents the most intense and unbearable pain. Evaluation will be conducted at weeks 4 and 12. The BPI 22 is a robust pain assessment tool widely utilized globally for clinical pain evaluation, epidemiological studies, and research on the efficacy of pain management interventions. The BPI evaluates the severity of pain over the past 24 hours or the past week (most severe, least severe, mean, and immediate pain levels), the impact of pain on daily functioning (including general activities, mood, walking ability, normal work performance, interpersonal relationships, sleep quality, and life satisfaction), pain location, analgesic usage, and pain relief magnitude. Each item is scored from 0 to 10, and the average score is calculated. The higher the score, the stronger the pain or the greater the degree of interference. Assessment time points: weeks 4, 8, and 12. The TCM Symptom Grading Quantitative Standard Score is an objective tool that classifies subjective TCM symptoms into four levels – “none, mild, moderate, severe”, and assigns corresponding scores (0–9 points). It transforms vague descriptions into quantifiable data, primarily used for clinical research and drug trials to scientifically evaluate the efficacy of TCM therapies. This method represents a crucial approach in the modernization of TCM, and the detailed scoring criteria are provided in the Table S3 in Attachment 3 of the supplementary materials . 23 , 24 Assessment time points: weeks 4, 8, and 12. The HADS 25 is an emotion screening scale specifically designed for general hospitals, comprising two sub-scales of anxiety and depression, each with 7 items, and using a 4-point scoring scale from 0 to 3. The two sub-scales are each scored from 0 to 21. An 8–10 score indicates a borderline case, while a score of 11 or higher suggests significant emotional abnormalities. The scale excludes interference from somatic symptoms and focuses on emotional and psychological experiences. It enables rapid assessment of anxiety and depression severity and is applicable for evaluating emotional states in hospitalized and outpatient patients as well as for research screening purposes. Assessment time points: weeks 4, 8, and 12. The EQ-5D-5L 26 is an internationally recognized universal tool for assessing quality of life. The scale includes questions across five dimensions (activity ability, self-care, daily activities, pain/discomfort, and anxiety/depression) as well as the EQ Visual Analogue Scale (EQ-VAS). Responses to questions are graded on a 5-point scale: no difficulty, slight difficulty, moderate difficulty, significant difficulty, and unable to complete/very severe. The EQ-VAS is a VAS scoring system ranging from 0 to 100, indicating the health status from the worst to the best possible. The health-related quality of life scores for respondents are calculated using the China EQ-5D-5L scoring formula, with higher scores indicating better health-related quality of life. Assessment time points: weeks 4, 8, and 12. The WHO QOL-BREF 27 is an internationally recognized simplified quality of life assessment tool, covering four domains: physiological, psychological, social relationships, and environment, with a total of 26 items and a 5-point scoring scale. The standardized score for each dimension = (the raw score of the dimension – the lowest score of the dimension)/(the highest score of the dimension – the lowest score of the dimension) × 100. The higher the score, the better the quality of life for that dimension. Assessment time points: weeks 4, 8, and 12. PGIC 28 ask patients to select from the following 7 descriptions that best describes how their symptoms have improved or worsened: 1-Significant improvement; 2-Improvement; 3-Slight improvement; 4-No change; 5-Slight exacerbation; 6-Exacerbation; 7-Significant exacerbation. Among them, 1 to 3 indicate symptom improvement, 4 indicates no change, and 5 to 7 indicate a worsening of the condition. Assessment time points: weeks 4, 8, and 12. This study is designed as a superiority randomized controlled trial with the VAS score as the primary outcome. Based on previous data and the minimal clinically important difference (MCID) of the VAS, 29 we assumed that the acupuncture combined with herbal cake-separated moxibustion group would show a mean reduction of 2.0 points on the VAS compared with the acupuncture group, with a pooled standard deviation of 0.73. Using a one-sided significance level of α=0.025, power of 80% (β=0.20), and a superiority margin of Δ=1.5, the formula for two-group comparison of means yielded 34 participants per group. Accounting for a 20% dropout rate, the final sample size was determined as 43 participants per group, totaling 86 participants. Eligible participants will be randomly assigned in a 1:1 ratio to either the experiment group or the control group. The randomization sequences is generated using SAS 9.3 software by an independent statistician not involved in trial implementation or statistical analysis. The group assignments are printed on cards and placed in sequentially numbered, opaque, sealed envelopes. The envelopes are prepared and kept by a research assistant who is not involved in participant recruitment or outcome assessment. After baseline assessments are completed, the next envelope in the sequence will be opened by acupuncturist to reveal the group allocation. The envelope is not resealable, and no envelope could be opened ahead of time. This study does not employ blinding for acupuncturists or participants. To minimize performance bias and contamination between groups under the non-blinded conditions, the two treatment modalities will be administered in separate, identically equipped rooms. Participants from different groups will have no contact with each other throughout the treatment sessions. This arrangement ensures that the potential confounding effects of patient expectations and practitioner distraction are equally distributed between the two groups. Outcome assessors and statisticians remain blinded to group allocation throughout the study. Before the study begins, we will standardize the design of Case Report Forms (CRFs) to clarify data collection criteria for acupuncture interventions (including acupoint selection, needle insertion depth, moxibustion positioning techniques, and physician qualifications) and outcomes, thereby minimizing data gaps and discrepancies. The data of trial will implement a dual-entry recording method with cross-verification protocols for data entry. Upon completion, dedicated data administrators will conduct logical reviews to promptly identify and address questions, with collaborative verification and corrections by research teams, ensuring full documentation throughout the process. Final data validation must be performed prior to locking to ensure no omissions or logical errors before data fixation, which cannot be modified arbitrarily post-locking. Concurrently, establish robust data security management protocols, including encrypted storage of trial data and restricted access controls to safeguard privacy and confidentiality. Experts in acupuncture, gynecology, statistics, and methodology reviewed and revised the trial protocol. Predefined standard operating procedures (SOPs) will be implemented for training relevant personnel. Appropriate communication with patients will be maintained to enhance compliance. When enrolling 10% and 90% of patients respectively, monitors will oversee trial progress and data collection. In case of abnormalities, corrective actions and evaluations will be strictly implemented in accordance with the trial’s SOP requirements. All data management records (eg, case report forms, modification logs) will be properly archived to ensure the reliability of trial outcomes. Statistical analysis will employ SAS 9.3 software. The intention-to-treat (ITT) principle will govern analyses of all randomized participants. Multiple imputation methods will handle missing data. Investigators will summarize measurement data using the mean ± standard deviation, median, and range (minimum to maximum values). Categorical and ordinal data will be reported as frequencies and percentages, respectively. For the primary outcome, a generalized linear mixed model (GLMM) for repeated measures will be fitted to compare the between group differences. For secondary outcomes, data distribution characteristics will determine approaches to group comparisons: independent t-tests will analyze normally distributed continuous data, while Mann–Whitney U -test will assess non-normally distributed continuous data; χ 2 -tests or Fisher’s exact test will evaluate categorical data; and nonparametric rank‑sum tests will examine ordinal data. For comparisons against baseline values, paired t-tests or Wilcoxon signed‑rank tests will apply to continuous data, and McNemar’s test (for binary data) or the Wilcoxon signed-rank test (for ordinal data) will be used for categorical data. All statistical procedures will use two-sided tests, and p < 0.05 will denote statistical significance. During the study period, non-inductive questions will be used at each visit to identify AEs from patients. AEs may also be reported voluntarily by patients during visits or identified through physical examination, laboratory tests, or other methods. The efficacy evaluator should meticulously document AE details on the CRF, including the AE name, occurrence and resolution dates, severity, relationship to interventions, impact on interventions, and outcomes. AEs associated with acupuncture and herbal cake-separated moxibustion include pain, hematoma, local infection, needle puncture, allergy and burns. This randomized controlled trial has obtained the registration number (ITMCTR2026000339) and will be conducted in accordance with the provisions of the Declaration of Helsinki. Recruitment personnel will be responsible for obtaining informed consent from patients. Patients may only be enrolled in the study after receiving detailed information about the research content and signing the informed consent form. The trial results will be published in a peer-reviewed academic journal.

In conclusion, the successful completion of this study will offer preliminary evidence supporting the safety and effectiveness of herbal cake‑separated moxibustion as an adjunct to acupuncture for managing CPP. These findings will provide reliable, direct data to support future large-scale trials.

Chronic pelvic pain is one of the core symptoms of SPID, characterized by high prevalence and significant diagnostic and therapeutic challenges. Approximately 10% to 20% of PID patients subsequently develop infertility, while 40% progress to CPP. 3 , 4 Its persistent presence not only severely impacts patients’ physical and mental health but also markedly reduces quality of life, making it one of the common gynecological conditions requiring urgent clinical intervention. 5 Current studies on acupuncture for chronic pelvic pain following pelvic inflammatory disease sequelae present notable methodological flaws that undermine evidence credibility. Most trials lack rigorous randomization, allocation concealment, blinding design, and standardized a priori sample size estimation, with generally small sample sizes. Inconsistent diagnostic criteria deviating from authoritative guidelines and non-standardized acupuncture protocols further impair research reproducibility. Additionally, these studies adopt simplistic, single-dimensional pain assessments, ignoring psychological and quality-of-life outcomes, with unified criteria for scale scoring and missing data management lacking. Without prospective registration, selective outcome reporting bias is prevalent. Deficient ethical procedures, incomplete adverse event documentation, and absent full-process quality control introduce substantial bias, rendering current evidence inadequate for reliable clinical decision-making. 30 , 31 The objective of this trial is to address the limitations of current clinical research by integrating the theory of syndrome differentiation and treatment in TCM with modern evidence-based medicine methodologies. For sample size calculation, this study referred to published evidence and minimal clinically important difference values to guarantee adequate statistical power. In terms of outcome evaluation, a comprehensive multidimensional assessment system was constructed incorporating the VAS, BPI, HADS, EQ-5D-5L, WHOQOL-BREF, quantitative grading criteria for TCM symptoms, and PGIC. This system synchronously quantifies pain severity, TCM syndromes, emotional status, health utility, and patients’ overall therapeutic perception. It enables a more comprehensive and objective evaluation of the holistic benefits of acupuncture treatment, effectively addressing the single-dimensional evaluation limitation observed in previous clinical studies. The strengths of this trial lie in its randomized controlled design, which effectively controls confounding factors and enhances the objectivity and reliability of research outcomes. Clear inclusion and exclusion criteria were established to ensure subject homogeneity and minimize bias. The study employed multidimensional evaluation metrics, including the VAS and the TCM syndrome scores, to comprehensively assess therapeutic efficacy and avoid the limitations of single-indicator assessments. However, the trial also presents certain limitations. Firstly, the limited duration makes it challenging to observe long-term efficacy and recurrence rates post-treatment; secondly, the blinding of both patients and acupuncturists was not feasible, a limitation frequently encountered in studies of this nature; additionally, the study focused solely on a single treatment regimen without investigating the impact of varying acupuncture parameters or herbal paste formulations on efficacy, necessitating further expansion of the generalizability of research conclusions.