Non-Invasive Auricular Acupoint Stimulation Improves Slow-Transit Constipation: Evidence From a Randomized Controlled Trial

Introduction

Slow-transit constipation (STC), a prevalent subtype of functional constipation, is characterized by a diminished colonic transport function [1]. The primary clinical symptoms include difficult defecation and prolonged defecation time, and are often accompanied by abdominal distension, abdominal pain, nausea, and vomiting [2]. In severe cases, it can lead to cardiovascular and cerebrovascular diseases, as well as mental and psychological issues [3]. According to the Rome IV criteria, the global prevalence of chronic constipation is approximately 10.1%, and this large patient population imposes heavy healthcare costs [4]. Current treatments include dietary fiber preparations, osmotic laxatives, stimulant laxatives, prokinetic drugs, and surgery. Long-term use of purgatives can lead to intestinal dysfunction, electrolyte disturbance, or dependence; the surgical indication is narrow, and some patients cannot undergo surgery due to complex conditions [5].

Thus, identifying safe, cost-effective, and mechanism-driven interventions remains an unmet clinical need.

Auricular acupoint stimulation, a non-invasive modality rooted in Traditional Chinese Medicine [6], has emerged as a promising approach for addressing a spectrum of conditions, including digestive disorders [7]. Mechanistically, auricular regions are hypothesized to modulate autonomic and enteric neural pathways via somato-visceral reflexes [8], potentially influencing gut motility and visceral sensitivity. Notably, the use of acupuncture for management of constipation has been endorsed by the World Health Organization [9]. Auricular acupoint stimulation offers distinct advantages: it avoids drug-related adverse effects, reduces treatment costs [10], and enhances patient compliance [11]. Combining acupoint stimulation with modern medicine may offer safer and more effective STC treatments.

Research has increasingly focused on the impact of auricular acupoint stimulation on constipation, but despite encouraging outcomes [12], the biological mechanisms – particularly its impact on neuroendocrine biomarkers like neuropeptide Y (NPY) and nitric oxide (NO) – remain unexplored. In this study, we conducted a distinct randomized, controlled intervention trial to elucidate the therapeutic efficacy and underlying mechanisms of auricular acupoint stimulation in treatment STC.

Material and Methods

STUDY DESIGN:

The research protocol adhered to STRICTA (Standards for Reporting Interventions in Controlled Trials of Acupuncture) and was approved by the Ethics Committee of the First Affiliated Hospital of Anhui University of Chinese Medicine (Ethical Approval Code: AH2022056001). Reporting followed the 25-item Consolidated Standards of Reporting Trials (CONSORT) checklist [13]. From March 1, 2022, through May 1, 2023, a total of 60 patients diagnosed with STC were enrolled and randomly allocated into the experimental and control cohorts by numerical table method. The eligibility criteria for participation were: 1) Conformity to the diagnostic benchmarks for STC as delineated in the Rome IV criteria; 2) Not taking any medication influencing gastrointestinal motility within the preceding 3 months; 3) Provision of informed consent after a comprehensive understanding of the study’s objectives; 4) Age 40–75 years. Exclusion criteria were: 1) Withdrawal from the therapeutic regimen; 2) Auricular pathologies; 3) Organic defecation disorder; 4) Pregnant or lactating. Both cohorts received standard care, which included a daily oral administration of prolucapride at a dose of 2 mg (manufactured by Jiangsu Hausen Pharmaceutical Co., LTD., China; National Medicine Approval number H20183482). Additionally, the study group underwent a supplementary regimen of auricular acupoint stimulation (Figure 1).

THE AURICULAR ACUPOINT STIMULATION PROCEDURE:

According to the Chinese national standard (GB/T13734-92) “Auricular point name and location”, the auricular acupoints were selected and located for this treatment, including: the small intestine (in the ear concha 6 area); the large intestine (in the ear concha 7 area); the rectum (in region 2 of the ear wheel, above the front spine of the helix root); and Shenmen points (in the upper part of the posterior 1/3 of the triangular fossa). The procedure involves disinfecting the ear with 75% medical alcohol. Subsequently, Cowherb (Vaccaria) seeds were affixed to the acupoints using tweezers and gentle pressure. Patients were instructed to apply manual pressure (5 sessions/day, 2 minutes/session) until mild discomfort was achieved. Each stimulation completed was recorded by the patient in the treatment notebook. This stimulation should be performed 5 times daily for 2 minutes each session. Seeds were replaced every 5 days, and the treatment duration was 20 days (Figure 2). Adverse events (eg, auricle skin rupture) were monitored, and affected patients were withdrawn.

SERUM NPY AND NO ASSAY:

A 3-mL sample of fasting venous elbow blood was collected before and after treatment, and centrifuged at 2500 rpm for 20 minutes to separate the serum. The supernatant was then extracted for quantification of NPY and NO concentrations using an ELISA kit (manufactured by Amresco, USA).

FECAL WATER ANALYSIS:

A temperature-controlled high-speed centrifuge (Thermo, UK) was employed to dehydrate the fecal sample at 40°C. Fecal water content was measured as the percentage of water loss relative to the initial sample weight.

GASTROINTESTINAL TRANSIT ASSESSMENT:

Patients ingested a single capsule containing 20 identical circular transit markers (Sitzmarks, produced by Anhui Yinggao Medical Equipment Co., LTD). Abdominal radiographs were taken 72 hours after ingestion. The 72-hour transit index (TI) was calculated to evaluate the colonic transit rate. The TI formula is as follows: 72h TI=SRM/(RCM+LCM+SRM), where RCM represents the number of markers in the right colic region, LCM in the left colic region, and SRM in the sigmoidorectal segment. The TI ranges from 0 to 1, with lower values indicating a reduced colonic transport capacity [14].

EFFICACY SCORING CRITERIA:

Symptoms were scored pre- and post-treatment based on defecation time (scored as follows: 0 for ≤5 minutes; 1 for >5 to ≤15 minutes; 2 for >15 to ≤25 minutes; and 3 for >25 minutes), and the inter defecation interval (scored as the number of hours divided by 24) was recorded. The efficacy index was calculated using the formula: [(pre-treatment score - post-treatment score)/pre-treatment score] ×100%.

STATISTICAL ANALYSIS:

Sample size was determined based on the minimal clinically important difference between groups. Data were analyzed using SPSS 26.0. Continuous variables were expressed as mean±standard deviation (χ̄±s) and compared using Student’s t-test (normal distribution) or Mann-Whitney U test (non-normal distribution). Categorical data were analyzed using the chi-square test. A two-tailed p-value ≤0.05 was considered statistically significant.

Results

BASELINE CHARACTERISTICS:

At baseline, the mean age of patients in the control group was 61.35±9.863 years, including 13 male patients. The duration of their disease was 64.26±9.484 months. In the study group, the mean age of patients was 60.55±9.0407 years, including 12 male patients. The duration of their disease was 67.08±15.183 months. No significant differences were observed in age (95% Confidence Interval: −3 to 6, P=0.4377), sex (95% Confidence Interval: −6.1393e-05 to 2.6102e-05, P=0.5426), or duration of disease (95% Confidence Interval: −12 to 2.4, P=0.7346) between the 2 groups (Figure 3). Each patient in the study group clearly recorded 100 effective stimuli in the treatment notebook.

THERAPEUTIC EFFECT COMPARISON BETWEEN TWO GROUPS:

There was no significant difference in defecation time and defecation interval scores between the study and control groups before treatment. However, after treatment, the scores decreased significantly in both groups, indicating a corresponding therapeutic effect. Post-treatment, the defecation time score was lower in the study group compared to the control group (Confidence Interval: 0.99998 to 5.9999, P=0.0150), and the defecation interval score was also lower in the study group (Confidence Interval: −8.2206e-06 to 1.0001, P=0.0498). The total effective rate was higher in the study group (93.3%) than in the control group (84.6%). In the study group, there were no side effects including auricle skin damage. (Figure 4)

BIOMARKER AND PHYSIOLOGICAL OUTCOMES:

Serum NPY and NO Levels: At baseline, NPY and NO concentrations did not differ between groups (P>0.05). Post-treatment, both groups showed reductions in NPY and NO levels (P<0.05), with the study group exhibiting significantly greater decreases compared to the control group (Table 1).

Fecal Water Content and Colonic Transit: Post-treatment, fecal water content increased in both groups, with a more pronounced improvement in the study group (P<0.05). The 72-hour transit index (TI) also improved significantly in the study group, indicating enhanced colonic motility (P<0.05).

Discussion

Our study demonstrates that Auricular Acupoint stimulation significantly alleviates symptoms of STC by modulating key neurotransmitters, including NPY and NO. We conducted randomized controlled clinical trials focusing on the stimulation of acupoints corresponding to the small intestine, large intestine, rectum, and the Shenmen point within the auricle. Our findings revealed a reduction in serum levels of NPY, which consequently decreased the availability of NPY for binding to peripheral choline acetyltransferase (pChAT) in the intestinal submucosal ganglia. NO, acting as a non-adrenergic, non-cholinergic neurotransmitter in the human digestive tract, was observed to increase, subsequently reducing intestinal motility. Hence, we propose that the mechanism by which Auricular Acupoint stimulation alleviates slow-transit constipation may be attributed to its influence on neurotransmitter activity.

STC, characterized by delayed passage of contents through the colon [15], is a chronic and primary functional colonic constipation resulting from impaired colon motility [16]. The exact etiology remains elusive, though it is believed to involve dysregulation of the enteric, central, and autonomic nervous systems, as well as abnormal hormone levels [17]. The prevailing view is that lifestyle factors such as irregular schedules, a fiber-deficient diet, dieting, and physical inactivity contribute to inadequate intestinal stimulation, leading to prolonged retention of stool. Animal studies indicate that acupuncture at LI 11, ST 37, ST 25, and BL 25 alleviates STC in mice, though abdominal stimulation may increase discomfort and complexity compared to auricular methods [18]. Current STC treatments rely on prokinetic agents like cisapride and prucalopride, but their long-term efficacy remains unproven, with symptom recurrence after discontinuation. Surgical options, such as colectomy, are limited by complications like adhesive ileus, diarrhea, and constipation recurrence, highlighting the need for safer, more effective therapies [19].

Auricular acupoint stimulation is classified within the domain of acupuncture methodologies [20]. This therapeutic approach, with roots in ancient China, boasts a venerable tradition [21]. Historical accounts from as far back as the Qin and Han Dynasties document the utilization of ear acupoints in medical treatment, and a coherent theory positing “the ear as the convergence of meridians” had already emerged by then [22]. Through its extensive evolution, auricular diagnosis and therapy have gained extensive application within the medical profession [23]. As a technique renowned for its safety, reliability, non-invasive nature, absence of damage, and lack of side effects, auricular acupoint stimulation is frequently employed in the management of conditions such as insomnia [24], various forms of pain [25], hypertension [26], obesity [27], primary nocturnal enuresis [28], polycystic ovary syndrome [29], and primary dysmenorrhea[30]. The efficacy of auricular acupoint stimulation may be attributed to its interplay with the autonomic nervous system, the Delta reflex theory, anti-inflammatory properties, and antioxidative effects [31]. A clinical trial design using auricular acupressure to treat constipation after tumor chemotherapy was limited to observation and lacked objective indicators of blood and intestinal movement [32]. A similar trial design using auricular acupressure for constipation had significant age differences between the groups [33]. Our clinical trial will complement these deficiencies.

Despite its promising results, our study has a limitation that the lack of direct intestinal tissue data precludes definitive conclusions about the local mechanisms of auricular acupoint stimulation. Future studies should incorporate biopsies or imaging techniques to assess changes in enteric neurons and smooth muscle activity.

Conclusions

This non-invasive auricular point stimulation has a significant improvement in symptoms in patients with STC, and the mechanism may be related to its effect on neurotransmitter activity.