Clinical study on auricular point sticking plus Western medicine for moderate gastric cancer pain

Chen Li-xia (陳麗霞), Yan Feng (閆峰)

Lin’an People’s Hospital Affiliated to Hangzhou Medical College, Zhejiang 323000, China

Abstract

Keywords: Acupoint Therapy; Auricular Point Sticking; Otopoint, Spleen (CO13); Otopoint, Stomach (CO4); Otopoint, Shenmen (TF4); Pain Measurement; Stomach Neoplasms; Cancer Pain

Gastric cancer is one of the most common malignant tumors in China, and the domestic numbers of both new and death cases each year are more than twice the world level[1]. Since the symptoms are not obvious in the early stage, and some patients just present mild stomachache and gastric distension, the early detection rate of gastric cancer is relatively low. Usually, patients have already been in the middle and late stages when they are diagnosed[2]. Cancer pain, one of the most common and difficult-to-control symptoms in the middle and late stages, will make patients suffer a lot and induce some negative moods such as anxiety and depression, further impair their physical and mental state as well as their quality of life, reduce their cooperation with treatment, and even impact the clinical efficacy of treatment[3]. In this regard, effectively relieving pain is of great significance.

The clinical treatment now mainly refers to the tri-step analgesia program formulated by World Health Organization (WHO). In this program, non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, weak opioids including codeine and dihydrocodeine, and strong opioids such as morphine and fentanyl are given to patients respectively according to their severity of cancer pain[4]. These drugs, however, can result in some adverse reactions including gastrointestinal reactions, central inhibition and respiratory depression, in addition to expensive price and being susceptible to addiction. As a result, they are not highly accepted[5].

Auricular point sticking is a crucial component of external therapy in traditional Chinese medicine (TCM). By stimulating the auricular points, this therapy can regulate Zang-fu organs, meridians and collaterals, and also balance qi, blood, yin and yang. Studies in recent years have suggested that auricular point sticking can effectively relieve cancer pain and drug adverse reactions[6], but few studies on its clinical efficacy and mechanism in treating moderate gastric cancer pain have been conducted. In this study, the clinical efficacy of treating moderate gastric cancer pain with auricular point sticking plus Western medicine was observed, and the patients’ cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) levels were detected to discuss the mechanism. The details are as follows.

1 Clinical Materials

1.1 Diagnostic criteria

The diagnostic criteria referred to theStandard for Diagnosis and Treatment of Gastric Cancer(2011 Edition)[7]and the diagnosis was confirmed by both imaging and pathology.

1.2 Inclusion criteria

Those who met the above diagnostic criteria; those who met the criteria of moderate cancer pain: with clear pain areas, and numeric rating scale (NRS) score between 4 and 6 points[8]; aged between 20 and 70 years old; estimated survival time ≥3 months; voluntary participation in this study and signed informed consent.

1.3 Exclusion criteria

Those with other serious primary diseases besides gastric cancer; women who were during pregnancy or lactation period; those who were allergic to the medicine taken in this trial; those with mental disorders and unable to cooperate with the completion of the trial.

1.4 Rejection and dropout criteria

Those who quit the trial voluntarily; those who presented serious adverse reactions or worse conditions; those with incomplete clinical materials and test data.

1.5 Statistical methods

The SPSS version 20.0 statistical software was adopted for data analysis, and the counting data were checked byχ2. The measurement data were expressed as mean ± standard deviation (±s). Pairedt-test was used for comparisons before and after treatment in the group while groupt-test was used for comparisons between groups.P<0.05 indicated statistical significance.

1.6 General data

A total of 80 cases with moderate gastric cancer pain who received treatment from the Lin’an People’s Hospital Affiliated to Hangzhou Medical College between January 2017 and May 2019 were recruited in the study. They were randomly divided into a control group and an observation group, with 40 cases in each group. No cases dropped out during treatment. Cases in the observation group were aged between 43 and 68 years old, with disease duration of 6-22 months, while cases in the control group were aged between 40 and 70 years old, with disease duration of 4-24 months. There were no significant between-group differences in gender, age and disease duration (allP>0.05), indicating that the two groups were comparable (Table 1).

Table 1. Comparison of general data between the two groups

2 Therapeutic Methods

2.1 Control group

According to the tri-step analgesia program, cases in the control group took tramadol hydrochloride sustained-release tablets (China Food and Drug Administration Approval Number: H19980214, Beijing Mundi Pharmaceutical Co., Ltd., China) orally for 2 weeks, 100 mg/time and once every 12 h. If the pain was not significantly relieved, the dosage could be increased properly with no more than 400 mg/d.

2.2 Observation group

Cases in the observation group received additional auricular point sticking on the basis of the same medicine treatment as that in the control group.

Auricular points: Stomach (CO4), Spleen (CO13), Shenmen (TF4), Sympathetic (AH6a) and Subcortex (AT4).

Methods:The patient took a sitting or supine position, and fully expose the auricle, which was sterilized with 75% alcohol cotton ball. Fixed the auricle with the left hand to stick adhesive plasters withWang Bu Liu Xing(Semen Vaccariae) to the above points with the tweezers using the right hand. Asked the patient to press the points with thumb and index finger 5 times a day, 2 min for each point, with strength making heaviness, numbness, distention and pain sensations. The two ears were treated alternately, and the ear was pressed once a day for 2 weeks.

3 Observation of Clinical Efficacy

3.1 Observed items

3.1.1 Score of NRS

Before and after the treatment, NRS was scored, which was between 0 and 10 points according to the severity of pain. 0 point suggested no pain while 10 points indicated the most severe pain[9]. The higher the score, the more severe the pain.

3.1.2 Details of cancer pain

The total time and flare-up times of pain during 24 h on the day before treatment and the next day after treatment were recorded.

3.1.3 Score of Karnofsky performance status (KPS)

Before and after the treatment, the patients in both groups were estimated quality of life by KPS score. The score was between 0 and 100 points, and the higher the score, the higher the quality of life[10].

3.1.4 COX-2 and TNF-α levels

Fasting venous blood of patients was obtained in the morning before and after treatment, and the COX-2 and TNF-α levels were detected via enzyme-linked immunosorbent assay (ELISA).

3.2 Efficacy criteria

The efficacy criteria referred to the NRS reduction rate[11].

Totally relieved: NRS reduction rate ≥90%.

Significantly relieved: NRS reduction rate ≥60%, <90%. Partially relieved: NRS reduction rate ≥30%, <60%. Not relieved: NRS reduction rate <30%.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The total effective rate of the observation group was 92.5% while the control group was 72.5%, withχ2=5.54,P=0.018. Check Table 2 for details.

Table 2. Comparison of clinical efficacy between the two groups (case)

3.3.2 Comparison of the NRS score

Before treatment, there was no significant difference between groups in the NRS score (P>0.05). After treatment, the scores significantly went down in both groups (bothP<0.05). The score of the observation group was significantly lower than that of the control group (P<0.05). Check Table 3 for details.

Table 3. Comparison of the NRS score between the two groups (±s, point)

Table 3. Comparison of the NRS score between the two groups (±s, point)

Note: Compared with the same group before treatment, 1) P<0.05; compared with the control group after treatment, 2) P<0.05

Group n Before treatment After treatment Observation 40 5.15±0.89 1.80±1.221)2) Control 40 4.98±0.86 2.78±1.371)

3.3.3 Comparison of the KPS score

Before treatment, there was no significant between- group difference in the KPS score (P>0.05). After treatment, the scores were significantly improved in both groups (bothP<0.05). The score of the observation group was significantly higher than that of the control group (P<0.05). Check Table 4 for details.

Table 4. Comparison of the KPS score between the two groups (±s, point)

Table 4. Comparison of the KPS score between the two groups (±s, point)

Note: Compared with the same group before treatment, 1) P<0.05; compared with the control group after treatment, 2) P<0.05

Group n Before treatment After treatment 40 53.25±11.63 83.50±13.311)2) 40 54.50±10.85 64.50±13.391) Observation Control

3.3.4 Comparison of cancer pain details

Before treatment, there were no significant differences between the two groups in the total time and flare-up times of pain during 24 h (bothP>0.05). After treatment, the total time and flare-up times of pain during 24 h of both groups were significantly reduced (allP<0.05), and were significantly lower in the observation group than in the control group (bothP<0.05). Check Table 5 for details.

Table 5. Comparisons of the total time and times of flare-up pain during 24 h between the two groups (±s)

Table 5. Comparisons of the total time and times of flare-up pain during 24 h between the two groups (±s)

Note: Compared with the same group before treatment, 1) P<0.05; compared with the control group after treatment, 2) P<0.05

Group n Time Total time of pain (h) Times of Flare-up pain (time) Observation 40 Before treatment 8.88±2.04 3.85±1.27 After treatment 2.23±1.531)2) 1.60±1.031)2) Control 40 Before treatment 9.30±2.05 4.05±1.43 After treatment 5.30±1.361) 2.53±1.541)

3.3.5 Comparisons of the COX-2 and TNF-α levels

Before treatment, there were no significant between- group differences in the COX-2 and TNF-α levels (bothP>0.05). After treatment, the COX-2 and TNF-α levels were significantly reduced in both groups (allP<0.05), and were significantly lower in the observation group than in the control group (bothP<0.05). Check Table 6 for details.

Table 6. Comparisons of the COX-2 and TNF-α levels between the two groups (±s)

Table 6. Comparisons of the COX-2 and TNF-α levels between the two groups (±s)

Note: Compared with the same group before treatment, 1) P<0.05; compared with the control group after treatment, 2) P<0.05

Group n Period COX-2 (ng/mL) TNF-α (ng/L) Observation 40 Before treatment 21.37±3.50 124.18±14.02 After treatment 10.15±2.141)2) 95.02±8.491)2)Control 40 Before treatment 21.02±3.39 124.59±13.68 After treatment 14.97±2.511) 110.22±12.451)

4 Discussion

The pathogenesis of cancer pain is complicated, involving qi stagnation, blood stasis, phlegm turbidity, pathogenic heat, and deficiency, which is, generally speaking, in two aspects: pain due to obstruction and pain due to deficiency of nourishment. Pain due to obstruction is an excess pain, mostly as a result of invasion of external pathogens and struggle between vital qi and pathogens, thus resulting in abnormal qi movements, qi stagnation, blood stasis, and obstruction in meridians. Pain due to deficiency of nourishment is a deficiency pain, which is usually caused by long-term disease duration, deficiency of vital qi, blood, yin and yang, and malnutrition of Zang-fu organs and meridians. Generally, obstruction is the common feature of its pathogenesis[12]. TCM holds that ‘no obstruction, no pain’, so unblocking meridians and collaterals, harmonizing qi and blood, and balancing yin and yang to promote circulation are the principle for treating cancer pain.

Auricular point sticking is a TCM external treatment mainly based on the close correlation between ears and Zang-fu organs as well as meridians and collaterals. Stimulating the related auricular points can regulate Zang-fu organs, unblock meridians and collaterals, balance yin and yang, in addition to activating blood flow and relieving pain[13]. In this study, auricular point sticking was given on the basis of medicine treatment. Stomach (CO4) and Spleen (CO13) were selected for regulating middle Jiao (energizer), harmonizing stomach, strengthening spleen and benefiting qi; Shenmen (TF4) for unblocking meridians and collaterals, regulating qi, activating blood flow and tranquilizing spirit; Sympathetic (AH6a) for regulating the autonomic nerve function, relieving pain and tranquilizing spirit; Subcortex (AT4) for regulating excitation and inhibition of cerebral cortex, and it is a critical point for relieving pain. The combination of the above points functions to unblock meridians and collaterals, activate blood, relieve pain and tranquilize spirit. In this study, the total effective rate of the observation group was higher than that of the control group (P<0.05); after treatment, the NRS scores of both groups were reduced (bothP<0.05), and was significantly lower in the observation group than in the control group (P<0.05); after treatment, the KPS scores of both groups were improved (both P<0.05), and was significantly higher in the observation group than in the control group (P<0.05). After treatment, the total time and flare-up times of pain during 24 h of both groups were significantly reduced (allP<0.05), and were significantly lower in the observation group than in the control group (bothP<0.05). All these results suggest that auricular point sticking combined with treatment of Western medicine can effectively relieve gastric cancer pain and improve patient’s quality of life. The clinical efficacy is superior to that of Western medicine alone.

Modern medicine holds that cancer pain is closely related to tumor itself, harmful treatment including surgery and chemotherapy, and moods of patients[14]. Though its pathological and physiological mechanism has not been clear until now, it is generally believed that the sensitivity of nerve will increase due to stimulation of nociceptor, thus resulting in decrease of pain threshold and increase of pain sensitivity, and giving rise to cancer pain[15].

Studies in recent years have suggested that COX-2 and TNF-α levels are closely related to cancer pain. COX-2 is an inducible enzyme and produced rapidly when stimulated by tumor microenvironment. It considerably promotes the synthesis of prostaglandin (PG), and thus produces inflammatory factors such as interleukin-6 (IL-6) and TNF-α. The combination of PG, inflammatory factors and primary afferent neuron related receptors can activate primary afferent neurons and induce hyperalgesia, giving rise to cancer pain[16]. Animal experiment suggested that COX-2 inhibitor can significantly relieve cancer pain of mice with bone tumor[17]. TNF-α, a kind of proinflammatory cytokines, can critically induce and aggravate cancer pain, in addition to stimulating monocyte macrophage to secrete IL-6 in large numbers. Inflammatory factors including TNF-α and IL-6 can accelerate the proliferation of tumor cells, promote the growth and metastasis of tumor and combine with ion channel protein of cell membrane, thus presenting pain signals and then transmitting them to the brain to generate pain[18]. Animal experiment also suggested that the TNF-α mRNA of the mouse inoculated with cancer cells was significantly increased, and injection of TNF-α monoclonal antibody can significantly inhibit cancer pain[19]. In this study, the COX-2 and TNF-α levels were significantly reduced in both groups (allP<0.05) after treatment, and were significantly lower in the observation group than in the control group (bothP<0.05), which suggested that auricular point sticking plus Western medicine treatment can effectively reduce the COX-2 and TNF-α levels of patients with moderate gastric cancer pain.

All in all, the clinical efficacy of auricular point sticking combined with Western medicine treatment for moderate gastric cancer pain is valid, as it can effectively relieve patients’ cancer pain and thus improve their quality of life. This may be related to the decrease of patients’ COX-2 and TNF-α levels.

Conflict of Interest

The authors declare that there is no conflict of interest.

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received: 19 September 2019/Accepted: 24 October 2019