Influence of herbal cake-partitioned moxibustion on lumbar functions and inflammatory factors in patients with lumbar disc herniation due to kidney deficiency and blood stasis

BI Dingyan (贲定严), LI Hongliang (李洪亮), HE Dao (何道), CAO Jianan (曹佳男), OUYANG Lizhi (欧阳里知),LIU Huijuan (刘惠娟), WANG Jing (王晶), YI Zhan (易展)

1 Hunan University of Chinese Medicine, Changsha 410208, China

2 The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China

3 Yueyang Hospital of Traditional Chinese Medicine, Yueyang 414000, China

Abstract

Keywords: Moxibustion Therapy; Indirect Moxibustion; Medicinal Cake-partitioned Moxibustion; Inflammatory Factors; Pain Measurement; Intervertebral Disc Displacement; Low Back Pain

Lumbar disc herniation (LDH) is commonly seen in clinical settings. Due to the rupture of the annulus fibrosus, the nucleus pulposus may bulge out to compress the nerve and subsequently lead to LDH. The main clinical manifestation is pain in the low back and legs. It is reported that 90% of LDH patients suffer from sciatica, and 50% of pain in the low back and legs is caused by LDH[1-2]. LDH can be induced by various factors, but the pathogenesis is not clear. Research suggests that obvious pain in the low back and legs will occur only when the inflamed nerve root is compressed.In this regard, inflammatory response in the pathogenesis of LDH has attracted more and more attention[3]. With changes in life style and the increase in work pressure, the incidence rate of LDH is increasing year by year, with a trend toward the young. LDH easily relapses and seriously influences the patient’s quality of life. Therefore, it is urgent to find a convenient, safe,and effective treatment. Dealing with LDH with acupuncture and moxibustion has been extensively and deeply studied, and positive results have been achieved.Herbal cake-partitioned moxibustion is a special moxibustion method. In this study, based on pattern differentiation and the etiology as well as the pathogenesis of LDH due to kidney deficiency and blood stasis, we made herbal cakes and treated the enrolled LDH patients with herbal cake-partitioned moxibustion.We compared this treatment with flour cakepartitioned moxibustion and Western medication alone to observe the influence of this method on the lumbar functions and inflammatory factors in these patients and evaluate its clinical efficacy.

1 Clinical Materials

1.1 Diagnostic criteria

The diagnostic criteria of Western medicine referred to theClinical Practice Guideline for Diagnosis and Treatment of Lumbar Disc Herniation[4]. The pattern differentiation criteria of traditional Chinese medicine(TCM) referred to the classification criteria of kidney deficiency and blood stasis in theGuiding Principles for Clinical Study of New Chinese Medicines[5]combined with clinical practice. Stabbing pain in the low back and legs with a fixed location and tenderness, and limited low back and leg movements; weakness in the low back and legs aggravated upon exertion and relieved after lying for rest; a pale purple or dark purple tongue with ecchymosis, and a thready hesitant or hesitant pulse.

1.2 Inclusion criteria

Those who met the diagnostic criteria and confirmed LDH by CT or MRI examination; aged between 20 and 60 years old, regardless of gender; were able to cooperate with the questionnaire survey; did not take analgesic and anti-inflammatory drugs or receive acupuncture a week before recruitment; signed informed consent.

1.3 Exclusion criteria

Those with severe nerve dysfunction, cauda equina nerve compression or surgical indications caused by nucleus pulposus protrusion; those with spinal stenosis and orthopedic diseases such as spinal fracture and ankylosing spondylitis; those with serious organic diseases involving heart, brain, kidney, blood, or tumor;those with mental diseases; those who were allergic to diflunisal tablets; females in pregnancy or lactation.

1.4 Statistical methods

The SPSS version 21.0 statistical software was adopted for data analysis. The counting data were expressed as case numbers or rates and were tested by Chi-square test. The measurement data conforming to normal distribution were expressed as mean ± standard deviation (±s). One-way analysis of variance was used for inter-group comparisons. The least significant difference was used for comparisons between the two groups, and the pairedt-test was used for intra-group comparisons; for the measurement data that did not conform to normal distribution, Friedman’s test was used for intra-group comparisons, and Kruskal-WallisH-test was used for inter-group comparisons and ranked data.P＜0.05 indicated statistical significance.

1.5 General data

We enrolled 120 patients with LDH due to kidney deficiency and blood stasis who visited the First Hospital of Hunan University of Chinese Medicine and Yueyang Hospital of Traditional Chinese Medicine between October 2019 and October 2020. They were randomly divided into the following three groups: a herbal cakepartitioned moxibustion group, a flour cake-partitioned moxibustion group, and a Western medication group,with 40 cases in each group. There were no statistical differences in such general data among the three groups as gender, age, disease duration, body mass index (BMI), and disease location (P＞0.05), indicating that the three groups were comparable. Check Table 1 for details. This study was reviewed and approved by the Ethics Committee of the First Hospital of Hunan University of Chinese Medicine (Approval No.HN-LL-LW-2019001).

Table 1. Comparison of the general data among the three groups

2 Methods

2.1 Western medication group

The patients in this group were treated with diflunisal tablets (250 mg, Batch No. 01190816, Zhengzhou Taifeng Pharmaceutical Co., Ltd., China), 0.5 g per dose,2 doses a day.

2.2 Herbal cake-partitioned moxibustion group

The patients in this group were treated with additional herbal cake-partitioned moxibustion.

Points: Bilateral Shenshu (BL23) and Geshu (BL17),and L3-L5Jiaji (EX-B2) Points.

Ingredients of the herbal cake:Shu Di Huang(Radix Rehmanniae Praeparata) 20 g,Bu Gu Zhi(Fructus Psoraleae) 15 g,Tu Si Zi(Semen Cuscutae) 15 g,Du Zhong(Cortex Eucommiae) 10 g,Gou Qi(Fructus Lycii)10 g,Dang Gui(Radix Angelicae Sinensis) 10g,Shan Yu Rou(Fructus Corni) 10 g,Rou Cong Rong(Herba Cistanches) 10 g,Mo Yao(Myrrha) 10 g,Du Huo(Radix Angelicae Pubescentis) 10 g,Hong Hua(Flos Carthami)6 g,Yan Hu Suo(Rhizoma Corydalis) 10 g,Chuan Xiong(Rhizoma Chuanxiong) 10 g, andBing Pian(Borneolum Syntheticum) 3 g. We ground the above medicinals into powder, sifted the powder with a 200-mesh sieve,added about 200 mL of rice wine, mixed them into a paste, then made a herbal cake with a thickness of 3 mm and a diameter of 1.0±0.2 cm, pricked 8-10 holes on it with a disposable filiform needle, and then sealed it in a ceramic pot.

Methods:We asked the patient to take a prone position, put the herbal cake on the points after routine disinfection, then placed the moxa cone (0.5 cm in diameter, 1.5 cm in height, and about 1 g in weight) on the herbal cake and lighted it. After the moxa cone was burned out, replaced it with another one, 4 moxa cones for each point. The moxibustion lasted for about 30 min,once a day.

2.3 Flour cake-partitioned moxibustion group

On the basis of Western medication treatment, the patients in this group were treated with additional flour cake-partitioned moxibustion. The points and methods were the same as those of the herbal cake-partitioned moxibustion group, except that the herbal cake was replaced by a flour cake. The main ingredient of the flour cake was wheat flour, and its size and hardness were roughly the same as those of the herbal cake.

All the patients were treated for 10 d.

3 Observation of Clinical Efficacy

3.1 Observed items

3.1.1 Visual analog scale (VAS) score

VAS was used to evaluate the pain severity of the patients. The higher the score, the more severe the pain[6].

3.1.2 Japanese Orthopaedic Association (JOA) score

JOA was used to evaluate the lumbar functions of the patients, with a total score of 29 points. The higher the score, the better the lumbar functions[7].

3.1.3 Interleukin (IL)-6, tumor necrosis factor (TNF)-α,and substance P (SP)

The radioimmunoassay was used to test the levels of TNF-α and SP. The kits were purchased from Real-Ab Medical & Pharmaceutical Technology Co., Ltd., China.Enzyme-linked immunosorbent assay was used to test the level of IL-6. The kits were purchased from Shanghai Hengyuan Biochemical Reagent Co., Ltd., China. The specific steps were carried out according to the instructions.

3.2 Efficacy evaluation criteria

We formulated the efficacy evaluation criteria and the scoring criteria of TCM symptoms according to the literature[5,8]. TCM symptoms were classified into four levels: none, mild, moderate, and severe, scored 0, 1, 2,and 3 points, respectively. The symptoms of the tongue and pulse were not scored. The total score and the reduction rate of TCM symptom score were calculated.The efficacy was evaluated after treatment.

Reduction rate of TCM symptom score = (Total symptom score before treatment - Total symptom score after treatment) ÷ Total symptom score before treatment × 100%.

Cured: The pain in the low back and legs almost disappeared. Straight leg raising test (SLRT) was negative. The patient was able to work normally, and the reduction rate of TCM symptom score was ≥95%.

Markedly effective: The pain in the low back and legs partially disappeared without obvious tenderness in the local area. SLRT was negative. The patient was almost able to work normally. The reduction rate of TCM symptom score was ≥70% but ＜95%.

Effective: There was mild pain in the low back and legs. SLRT was (±). The patient was able to do part of the work. The reduction rate of TCM symptom score was ≥30% but ＜70%.

Invalid: The pain in the low back and legs was not relieved. SLRT was positive. The patient was not able to work. The reduction rate of TCM symptom score was＜30%.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The total effective rate of the herbal cake-partitioned moxibustion group was 92.5%, that of the flour cake-partitioned moxibustion group was 80.0%, while that of the Western medication group was 72.5%. The curative effect of the herbal cake-partitioned moxibustion group was better than that of the other two groups (P＜0.05). Check Table 2 for details.

3.3.2 Comparison of the VAS and JOA scores

There was no statistical significance in comparing the VAS or JOA scores among the three groups before treatment (P＞0.05). After treatment, the VAS scores of the three groups were lower than those before treatment, and the JOA scores were higher than those before treatment, indicating intra-group statistical significance (P＜0.05). After treatment, the VAS score of the cake-partitioned moxibustion group was lower than that of the other two groups, while the JOA score was higher than that of the other two groups (P＜0.05).Check Table 3 for details.

3.3.3 Comparison of the serum inflammatory factors

There was no statistically significant difference in the levels of IL-6, TNF-α, or SP among the three groups before treatment (P＞0.05). The levels of IL-6, TNF-α,and SP of the three groups after treatment were lower than those before treatment, indicating intra-group statistical significance (P＜0.05). After treatment, the levels of IL-6, TNF-α, and SP of the herbal cake-partitioned group were lower than those of the other two groups (P＜0.05). Check Table 4 for details.

Table 2. Comparison of the clinical efficacy among the three groups (case)

Table 3. Comparison of the VAS and JOA scores among the three groups before and after treatment ( ±s, point)

Table 3. Comparison of the VAS and JOA scores among the three groups before and after treatment ( ±s, point)

Note: VAS=Visual analog scale; JOA=Japanese Orthopaedic Association; compared with the group before treatment, 1) P＜0.05; compared with the flour cake-partitioned moxibustion group and the Western medication group after treatment, 2) P＜0.05

Group n VAS JOA Before treatment After treatment Before treatment After treatment Herbal cake-partitioned moxibustion 40 6.2±1.7 2.4±0.61)2) 14.9±3.2 23.8±3.91)2)Flour cake-partitioned moxibustion 40 6.1±1.5 3.2±0.81) 15.3±3.4 20.6±4.11)Western medication 40 5.9±1.4 3.5±0.91) 15.7±2.8 19.4±3.31)

Table 4. Comparison of the serum inflammatory factor levels before and after treatment among the three groups ( ±s)

Table 4. Comparison of the serum inflammatory factor levels before and after treatment among the three groups ( ±s)

Note: IL-6=Interleukin-6; TNF-α=Tumor necrosis factor-α; BT=Before treatment; AT=After treatment; compared with the group before treatment, 1) P＜0.05, compared with the flour cake-partitioned moxibustion group and Western medication group after treatment, 2) P＜0.05

Group n IL-6 (pg/mL) TNF-α (ng/L) Substance P (ng/L)BT AT BT AT BT AT Herbal cake-partitioned moxibustion 40 24.2±4.7 13.1±2.21)2) 21.6±4.8 10.2±2.71)2) 42.2±6.1 22.7±3.81)2)Flour cake-partitioned moxibustion 40 23.4±4.4 16.5±2.61) 20.2±5.3 13.8±2.21) 41.5±5.6 26.2±4.41)Western medication 40 23.7±5.2 17.3±3.11) 20.9±5.2 14.5±3.31) 41.8±6.7 27.6±4.91)

4 Discussion

As a common spinal disease, LDH may cause pain in the back and low back and radiculalgia[9]. According to its clinical manifestations, it falls under the categories of“low back pain” and “Bi-Impediment syndrome” in TCM.It is mainly caused by injury and impediment, with the nature of a deficient root. Stasis exists throughout its duration. The dull pain in the early stage, the swelling and stabbing pain in the middle stage, and the numbness and lassitude in the later stage are all related to blood circulation. In addition, with the growth of age,deficient kidney Qi may fail to nourish tendons and bones. Consequently, tendons and bones may be easy to get injured by external forces, causing local Qi stagnation and blood stasis and subsequent low back pain. Therefore, kidney Qi deficiency and blood stasis are the important pathogenesis of LDH. In this regard,the main treatment principles are to tonify the kidney,strengthen tendons and low back, promote blood circulation, remove stasis, and relieve pain.

Based on pattern differentiation, in this study,Shenshu (BL23) and Geshu (BL17) were selected to tonify the kidney, strengthen the low back, promote blood circulation, and remove stasis. Connected with the Governor Vessel and the Bladder Meridian, the L3-L5Jiaji (EX-B2) Points can activate Yang Qi, unblock local meridians, promote blood circulation, regulate Qi, and relieve pain. Needling these points can alleviate the pain induced by LDH and change the biomechanics in the lumbodorsal muscles[10].

Moxibustion can warm Yang and tonify Qi, thus especially suitable for deficiency and cold patterns[11].Herbal cake-partitioned moxibustion is a kind of indirect moxibustion. The medicinal properties of mugwort leaves and other herbs can penetrate skin into the disease location through warm stimulation[12]. The prescription of the herbal cake in this study is mainly based on Bu Shen Huo Xue Tang (kidney-tonifying and blood-activating decoction).Shu Di Huang,Bu Gu Zhi,

Tu Si Zi,Du Zhong,Gou Qi,Shan Yu Rou, andRou Cong Rongcan nourish blood and strengthen tendons and bones;Dang Gui,Mo Yao,Du Huo,andHong Huacan promote blood circulation, remove stasis, unblock collaterals, and relieve pain, and their functions can be strengthened under the help ofYan Hu SuoandChuan Xiong; the aromaticBing Piancan help the body absorb the properties of the herbs[13]; rice wine can help promote blood circulation and unblock meridians. The combination of all these ingredients can tonify the kidney, strengthen tendons, promote blood circulation,and relieve pain.

Modern medicine holds that such clinical manifestations of LDH as inflammatory reactions, low back pain, leg pain, and lumbar dysfunction are mainly induced by nucleus pulposus herniation that compresses the nerve root[14]. Clinically, VAS is often used to evaluate pain severity and development, and JOA is used to evaluate clinical symptoms and lumbar functions[15]. In this study, after 10 d of treatment, the VAS score of the three groups decreased and the JOA score increased. It is similar to the result of the study conducted by SHAO Y Y,et al[16]. This result suggests that the patients’ low back pain is relieved and the lumbar function is improved, which may be related to the analgesic and anti-inflammatory effects of diflunisal tablets. The efficacy of the herbal cake- partitioned moxibustion group is better than that of the Western medication group and the flour cake- partitioned moxibustion group. This result shows that partitioned moxibustion based on the Western medication treatment can enhance the treatment effect, which may be related to the fact that moxibustion can relieve the pain in LDH patients and improve their lumbar functions[17]; this result also suggests thatBing Piancan promote the effect of the herbal cake and thus improve the treatment effect. In addition, the total effective rate of the herbal cake-partitioned moxibustion group was higher than that of the other two groups, showing the significant effect of herbal cake-partitioned moxibustion in the treatment of LDH due to kidney deficiency and blood stasis.

Inflammatory factors may induce sterile inflammation when the intervertebral disc is worn and compressed, leading to tissue ischemia and hypoxia, as well as the secretion of C-reactive protein, IL-6, etc. This condition may cause joint injury, stimulate spinal nerve endings, and subsequently induce pain in the low back and legs, as well as radiating pain in the lower limbs[18].TNF-α can promote T cells to produce various inflammatory factors and subsequently promote the chronic inflammatory reaction of the glands around the lumbar spine. IL-6 is a versatile pleiotropic cytokine. In addition to regulating immune response, it plays an important role in inflammatory responses. SP is widely distributed in the central and peripheral nervous systems, and its main role is to transmit pain information.

The levels of TNF-α and IL-6 in LDH patients were significantly higher than those in the people without this condition, and SP and IL-6 aggregated in the intervertebral disc and adjacent tissue, suggesting that TNF-α, IL-6, and SP may promote the occurrence and development of inflammation and participate in the degeneration of lumbar intervertebral disc and the generation of radiculalgia[19-20]. Therefore, to treat LDH,priority should be given to eliminating inflammatory radiculalgia. In this study, the levels of IL-6, TNF-α, and SP of the three groups were lower than those before treatment, suggesting that the inflammatory response is suppressed, which is similar to the results of the study conducted by SONG J W,et al[14]. This may be related to the fact that diflunisal tablets can inhibit cyclooxygenase and thus block the synthesis of prostaglandins to relieve pain and inflammation. After treatment, the levels of IL-6, TNF-α, and SP of the herbal cake-partitioned moxibustion group were lower than those of the flour cake-partitioned moxibustion group and the Western medication group. This is because that moxibustion can treat inflammatory diseases by regulating inflammatory reactions and autophagy[21]. In addition, the herbal cake can strengthen the anti-inflammatory effect of moxibustion.The results of this study suggest that the treatment of the herbal cake-partitioned moxibustion group may inhibit the inflammatory reaction, thus alleviating the pain and improving the patient’s lumbar functions by reducing the levels of TNF-α, IL-6, and SP.

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

This work was supported by Project of Hunan Provincial Natural Science Foundation of China (湖南省自然科学基金项目, No. 2021JJ40396); Scientific Research Project of Department of Education of Hunan Province (湖南省教育厅科学研究项目, No. 19C1397).

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received: 14 September 2020/Accepted: 22 April 2021