Chao Liang,Cai-Yu Peng,Tao Jiang,Shao-Ping Chen,Yan-Zhen Zhang,Meng-Rui Zhang

1Haikou Hospital of Traditional Chinese Medicine,Hainan Haikou 570216,China.

Abstract

Background:Lumbar disc herniation is the most common back pain disorder characterized by lumbago-leg pain in clinical practice.The treatment of lumbar disc herniation in Western medicine mainly contains the operative or non-operative interventions (nerve block therapy, etc.) to relieve pain.Although the pain relief is fast and the short-term effect is clear, it often ignores the degeneration of intervertebral disc, resulting in recurrent symptoms,prolonged course of treatment, and easy to cause sequelae such as lumbar instability.Acupuncture has been used for a long time in the clinical treatment of lumbago-leg pain with definite and long-lasting effect.Methods: 116 cases of lumbar disc herniation were randomly divided into treatment group (n = 59) and control group (n = 57).The control group was treated with oral analgesics, and the observation group was treated with “Tongji”electro-acupuncture (the acupoints were selected at 1.3 inch away from the midline after level T12 (the 12th thoracic vertebra),L1(the 1st lumbar vertebra),L2(the 2nd lumbar vertebra),L3(the 3rd lumbar vertebra),L4(the 4th lumbar vertebra), L5 (the 5th lumbar vertebra) and S1 (the 1st sacral vertebra), the left and right sides are symmetrical) plus oral analgesics.Ⅴisual analog scale score and Japanese Orthopaedic Association score were evaluated before treatment and 5 days, 10 days and 1 month after treatment, respectively.The contents of interleukin-6 and substance P in peripheral serum were detected by enzyme-linked immunosorbent assay method,and the total clinical effective rate was calculated.Results: Both the pain visual analog scale score and Japanese Orthopaedic Association score in the treatment group and the control group after treatment were improved as compared with those before treatment (P ＜0.05).There were also significant differences in these two scores between the treatment group and the control group (P ＜0.05).Furthermore, there was no significant difference between 1 month and 10 days after treatment (P ＞ 0.05), indicating the long-term effect of “Tongji”electroacupuncture on improving lumbago-leg pain was significant.After treatment, the contents of interleukin-6 and substance P in both the control group and the treatment group were lower than those before treatment,and there was significant difference between the control group and the treatment group(P ＜0.05 and P ＜0.01 respectively).The total effective rate after treatment was 94.92%,which was higher than that of 87.72%in the control group(P ＜0.01).Conclusion:The intervention of“Tongji”electroacupuncture plus the routine oral analgesic can significantly improve the lumbar function of patients with lumbar disc herniation, alleviate the pain and improve the clinical symptoms of lumbar disc herniation via decreasing the production of inflammatory factors interleukin-6 and substance P,suggesting a better curative effect than oral analgesic alone.

Keywords:“Tongji”electroacupuncture,Lumbar disc herniation,Back pain,Interleukin-6,Substance P

Background

Lumbar disc herniation(LDH),the most common back pain disorder in clinical practice, is known as the rupture of the fibrous annulus of lumbar intervertebral disc or nucleus pulposus herniation of lumbar intervertebral disc, is a common disease of lumbar and leg pain caused by nucleus pulposus protrusion and compression of spinal nerve root after rupturing of the fibrous annulus between vertebral bodies [1].Due to the degenerative changes of the lumbar spine, the aging of the intervertebral disc and the calcification of the ligaments around the lumbar spine and the incidence of the disease is increasing and showing a trend of younger development.The treatment of LDH in western medicine is mainly through an operative intervention, mainly by foraminal endoscopic nucleus pulposus removal, simple interlaminar windowing nucleus pulposus removal, semi-(total) laminectomy and interbody fusion [2].Although it can relieve the symptoms, it affects the biomechanical stability of the lumbar spine, which is easy to cause secondary spinal canal stenosis or adhesion of the dural sac and nerve root.Modern studies have shown that intervertebral disc degeneration occurs with age, which initiates the inflammatory-immune mechanism and promotes nucleus pulposus cell apoptosis under the interaction of mechanical stimulation and physical and chemical factors [3–4].Because interleukin-6 is associated with the risk of LDH and directly reflects the intensity of inflammation, it can be considered as one of the observation indicators to judge the degree of intervertebral disc degeneration or injury.

Now, more and more patients with LDH are turning to non-operative treatments.Acupuncture is clinically regarded as the first choice in the non-operative treatments of LDH,especially for local lumbar pain[5].Our previous studies [6] also confirmed that electroacupuncture at Backshu acupoint and Jiaji acupoint can significantly alleviate the clinical pain symptoms of LDH patients and improve the symptoms of sciatic nerve compression, but the cure rate of numbness in buttocks and legs is relatively low, and the duration of analgesic effect is relatively short.The same conditions usually occur in many patients again within 3–4 weeks after the end of treatment [7].Therefore, in this study, “Tongji” electroacupuncture(the acupoints were selected at 1.3 inch away from the midline after level T12 (the 12th thoracic vertebra), L1(the 1st lumbar vertebra),L2(the 2nd lumbar vertebra),L3 (the 3rd lumbar vertebra), L4 (the 4th lumbar vertebra), L5 (the 5th lumbar vertebra) and S1 (the 1st sacral vertebra), and the left and right sides are symmetrical) was used to treat LDH patients in remission stage, and its efficacy and safety were further observed through clinical control study, to provide a certain clinical basis for the treatment of lumbar disc herniation.

Clinical data

Research objects

All the 120 cases were collected from the Department of Acupuncture and Rehabilitation of Haikou Traditional Chinese Medicine Hospital from January 2019 to June 2020,which met the diagnostic criteria of lumbar disc herniation.

Diagnostic criteria

Diagnostic criteria of Western medicine: according to the Guidelines for theDiagnosis and Treatment of Lumbar Disc Herniation[8] formulated by the Spinal Surgery Group of the Orthopaedic Association of the Chinese Medical Association and the Orthopaedic Rehabilitation Group of the Orthopaedic Association of the Chinese Medical in 2020.

Clinical manifestations.①M(fèi)ostly seen in young and middle-aged men, especially those bending-over manual workers.② Low back pain with lower extremity sciatic nerve radiation pain symptoms.Low back pain and lower limb pain are typical in the distribution area of lumbosacral nerve roots.

Physical signs.Lumbar deformity, limitation of lumbar activity, tenderness and percussion in lumbar vertebrae or lumbar, spinous process, etc.There were obvious tenderness points on the side of the interspinous ligament in L4, L5 or L5 and S1.According to the nerve distribution area, there were two signs of muscle atrophy, muscle strength weakening, sensory abnormality and reflex change,with straight leg raising test(+), strengthening test (+),neck flexion test(+).

Imaging examination.Scoliosis and lumbar kyphosis become shallower,the diseased intervertebral disc may become narrower, and there is osteophyte hyperplasia at the corresponding edge.Computed tomography magnetic resonance imaging examination can show the location and degree of intervertebral disc herniation.

Syndrome diagnosis of traditional Chinese medicine.According to the blood stasis syndrome type (blood stasis refers to a syndrome type in syndrome differentiation in traditional Chinese medicine.) of lumbar disc herniation in theDiagnostic and Therapeutic Standard of Diseases and Syndromes in Traditional Chinese Medicine[9] issued by the State Administration of Traditional Chinese Medicine in 1994,tingling pain in the waist and the fixed sore point refuses to be pressed.The pain is mild during the day and heavy at night.Symptoms include stiff waist,limited movement, dark purple tongue, or ecchymosis,and tight or astringent pulse.

Inclusion criteria

①Those who meet the diagnostic standard of low back pain in traditional Chinese medicine and lumbar disc herniation in western medicine.②Duration of LDH within 2 to 3 weeks and in the remission period.③Those aged 18–65, regardless of gender.④Those who are informed and signed written informed consent.

Figure 1 Study path diagram.ⅤAS, visual analog scale; JOA, Japanese Orthopaedic Association; IL-6,interleukin-6;SP,substance P.

Exclusion criteria

①Those who do not meet the diagnostic criteria of low back pain in traditional Chinese medicine and lumbar disc herniation in western medicine.②Those who belong to patients with prolapse or dissociation of the intervertebral disc, or lumbar spondylolisthesis Ⅱ°or above according to pathological classification.③Those with simple abnormal imaging findings, but without clinical symptoms of lumbar disc herniation.④Those with lumbar fracture, bone fracture, lumbar tuberculosis, abscess or space-occupying lesion of lumbar vertebrae.⑤ Those who are pregnant or lactating women.⑥those who have mental disorders and severe primary diseases such as heart,liver,kidney,hematopoietic system and endocrine system.⑦Those who are treated with other methods.

Randomized controlled design

SPSS22.0 statistical software is used to make a random table, by which the random distribution card is filled and sealed in a special opaque cowhide envelope.If the patient meets the inclusion criteria, the envelope is opened and studied according to the contents of the random table.

Sample size

The estimation formula of sample size is n = 2 × (Uα＋ Uβ)2 × P(1-P)/δ2.The sample sizes of the test group and the control group are distributed in equal proportion.Taking into account the shedding factor,the number of cases is increased appropriately by 15%–20%.Therefore,there are 60 cases in each group,120 cases in total.In the course of the experiment, 1 case fell off in the treatment group (the patient was unable to walk because of acute low back pain, and was performed), 3 cases fell off in the control group(1 case could not receive treatment on time due to work reasons; 1 case withdrew from treatment because of poor efficacy, and 1 case took painkillers without authorization).According to the intention-to-treat analysis, 59 cases were in the treatment group and 57 cases in the control group.

Ethics

The clinical trial was approved by the Ethics Committee of Haikou Branch of Yueyang Integrated Traditional Chinese and Western Medicine Hospital affiliated to Shanghai University of Traditional Chinese Medicine (Approval time:Apr.02,2020).The implementation of the experiment complies with World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects, 2004.All patients entered the trial stage after signing the informed consent form.

Treatment methods

The control group

Patients were treated with diclofenac sodium double release enteric-coated capsule (Boehringer Ingelheim Pharma company, Germany), 75 mg once a day for 10 days.

The observation group

Patients were treated with“Tongji”electroacupuncture,once a day for 10 days, plus oral analgesics same as that of the control group.

The acupoints were selected at 1.3 inch away from the midline after level T12,L1,L2,L3,L4,L5 and S1,and the left and right sides are symmetrical.

Operation

Spinal penetratio n needling method: the patient took a prone position or lateral recumbent position, the acupuncture needles were twirled and obliquely inserted into the subcutaneous 1.3 inch by neutral supplementation and draining method.Puncture the points and try to penetrate the vertebral lamina and stab the nerve trunk.The specific depth of acupuncture depends on the degree of fatness and thickness of muscle of patients.The needles handle located on the ipsilateral L3 and L5 were respectively connected to the G-r6805a electroacupuncture stimulator (Shantou Medical Equipment Co.,Ltd.,China).Dense wave and stimulation parameters were FM wave 15/100Hz,intensity 1 ～2mA,for 30min.

Needles

φ0.25×75mm Huatuo stainless steel disposable acupuncture needle (Suzhou Medical Supplies Factory Co.LTD,China).

Treatment course and treatment time

Once a day for 10 days.

Observation indexes

Primary indexes

The visual analog scale (VAS) score [10].With a 10 cm scale, 0 represents complete painless, while 10 represents the most severe pain.The patient marks the corresponding position of pain on the scale, and then the value of pain intensity is measured.

Lumbar Japanese Orthopaedic Association (JOA)score [11].The modified JOA was used for comprehensive evaluation:it is composed of four parts,which could be roughly divided into subjective symptoms,objective signs,limitation of daily activities and voiding function.The total score was calculated after all questions were answered.

Evaluation standard for curative effect.According to theDiagnostic and Therapeutic Standard of Diseases and Syndromes in Traditional Chinese Medicine[9]formulated by the State Administration of Traditional Chinese Medicine, cured: subjective symptoms such as lumbago-leg pain disappears,straight leg raising test is negative, and the patient return to normal work.Obvious effect: subjective symptoms such as lumbago-leg pain disappears,straight leg raising test is close to 70, and the patient return to normal work.Effective: Compared with previous conditions, the symptoms partially disappear,the movement is slightly limited and the straight leg raising test is improved.Even: the patient can take on lighter jobs.Ineffective: no improvement was found in symptoms and signs, and the patients were still incompetent for jobs.Total effective rate = (cured cases+obvious effective cases+improved cases)/total cases × 100%.

Secondary indexes

Measurement of serum interleukin-6 (IL-6) and substance P (SP) content.5 mL of blood samples were collected from elbow vein.After the centrifugation treatment of 3000 r/min for 5 min, the serum was collected and stored at -20℃for testing.Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of IL-6 and SP (Wuhan Boshide Biological Co., Ltd., China) and the optical density value was determined by the American BIOTRAK-Ⅱautomatic enzyme labeling instrument.Double antibody sandwich method was used in this experiment.The anti-human IL-6/apolipoprotein-1(APO-1) and SP/APO-1 monoclonal antibodies were coated on the enzyme plate.The corresponding human antibodies in the standard and sample were combined with the monoclonal antibodies, and the biotinylated anti-human antibody was added to form an immune complex attached to the plate.After binding the streptavidin labeled by horseradish peroxidase to biotin,the enzyme-substrate tetramethylbenzidine was added to blue, and then turned yellow after adding the terminating liquid sulfuric acid.The optical density value was measured as 450 nm, and the concentration of IL-6/APO-1 and SP/APO-1 in humans in the sample was calculated by drawing a calibration curve.

Evaluation time

All indexes were evaluated before treatment, 5 days after treatment, 10 days after treatment, and 1 month after treatment.

Statistical analysis

SPSS22.0 software was used for statistical analysis.The measurement data were expressed as mean ±standard deviation (mean ± standard deviation).t-test was used for inter-group comparison between two independent samples.Paired sample t-test was used for intra-group comparison, andχ2test and rank-sum test were used for counting data.The difference was statistically significant whenP＜0.05.

Results

Baseline data analysis

There was no significant difference in gender, age and course of disease between the treatment group(n=59)and the control group(n=57)(P＞0.05)(Table 1).

VAS score

Though no significant difference was found in ⅤAS score before treatment(P＞0.05),the ⅤAS score in the observation group decreased significantly 5 days after treatment (P＜ 0.01), 10 days and 1 month after treatment respectively(P＜ 0.01) (Table 2).By intra-group comparison, it was found that the ⅤAS score 1 month after treatment was the lowest,indicating the analgesic effect could lasted until 1 month after the end of treatment (compared with 10 days after treatment,P＞0.05).

Lumbar JOA score

It can be seen from Table 3 that there was no significant difference in the JOA score between the two groups before treatment (P＞0.05), but the JOA score in the observation group was significantly higher than that in the control group 10 days after treatment(P＜0.01), indicating that “Tongji” electroacupuncture plus oral analgesics can significantly improve the lumbar function of LDH patients.One month after treatment, there was a significant difference in the score between the treatment group and the control group(P＜0.01).It showed that the long-term effect of this treatment is better than that of drug therapy.The intra-group comparison found that the JOA score of the treatment group increased significantly 10 days after treatment (P＜0.01), and the JOA score remained at a high level 1 month after treatment, indicating that“Tongji” electroacupuncture has significant short-term and long-term effects on relieving lumbago-leg pain and improving lumbar function.

Curative effect

The total effective rate was 94.92% in the treatment group and 87.72% in the control group, and the difference was statistically significant (P＜ 0.01)(Table 4), indicating that the curative effect of the treatment group was better than that of the control group.

Level of IL-6 and SP

There was no significant difference in the contents of IL-6 and SP between the two groups before treatment(P＞0.05),but a drop in the levels of IL-6 and SP(P＜0.01), and there was also a significant difference compared with the control group on 10 days and 1 month after treatment(P＜0.01,P＜0.05 respectively)(Table 5 and Table 6).

Table 1 Comparison of general clinical data between the two groups(mean ± SD)

Table 2 Visual analogue scale score(mean ± SD)

Table 3 Comparison of lumbar Japanese Orthopaedic Association score(mean ± SD)

Table 4 Comparison of total effective rate

Table 5 Comparison of interleukin-6 level(mean ± SD,μg/L)

Table 6 Comparison of substance P level(mean ± SD,ng/mL)

Discussion

Clinical data demonstrated about 1/3 of LDH patients presented with low back pain and leg pain and numbness at the same time, but the low rates of cure rates severely affect daily living and quality of life in patients.This is because the nucleus pulposus tissue includes notochord cells and cartilage-like cells have similar cytological morphology to articular chondrocytes and can express Sox9, type Ⅱcollagen and cartilage proteoglycan mRNA) [12].With aging the notochordal cell population is replaced by cartilage-like cell population.

Degeneration of an intervertebral disc involves some changes of the nucleus pulposus, mostly concerned with the number, structure and extracellular matrix components [13].The interaction of mechanical stimulation and physical and chemical factors can activate the expression of target genes in the upper and lower part of the intervertebral disc to degrade the extracellular matrix, make the nucleus pulposus tissue break through the annulus fibrosus or posterior longitudinal ligament, and initiate the inflammatory-immune mechanism to trigger apoptosis[14].Previous studies have shown that inflammation factors are the main reason which causes apoptosis in the intervertebral disc, in which the IL-Fas-FasL molecular signal pathway is the main pathway.The expression of interleukin series factors is found in normal and degenerative human intervertebral disc tissue [15–16].The content of IL in peripheral blood have also been found in patients with discogenic low back pain.Meanwhile, a certain amount of FasL plays the role of inflammatory factors, induces a series of IL factors,aggravates the immune-inflammatory response,and promotes the apoptosis of nucleus pulposus cells[17].This is the major factor of intervertebral disc degeneration.Therefore, our study focused on the mechanism of intervertebral disc inflammation,and we can judge the analgesic and inflammatory inhibitory effect of “Tongji” electroacupuncture by observing the change of IL-6 and SP content.From an experimental point of view,“Tongji”electroacupuncture had a direct inhibitory effect on the secretion of inflammatory factor IL-6 and painful substance SP.The content of both began to decrease after treatment 5 days, and the inhibitory effect lasted until the end of treatment and remained at a low level during the one-month follow-up period.The JOA score showed that the subjective symptoms of patients with clinical waist and leg discomfort were significantly reduced, and the self-care ability was also significantly improved.

Lumbar disc herniation belongs to the category of“l(fā)ow back pain” and “arthralgia syndrome” in traditional Chinese medicine.Acupuncture has achieved a good curative effect in the treatment of lumbar disc herniation with the principles of dredging or nourishing meridians and has become the first treatment of lumbar disc herniation [18].Acupuncture at Jiaji acupoints(Ex-B2)has been extensively used in clinical practice in the treatment of the disease.Jiaji acupoints (Ex-B2) is located 1.6 cm beside the spine,and its circulation is exactly where the governor meridian and bladder meridian are covered by the extension of Qi.Therefore,stimulating this acupoint to treat low back pain could play a role to regulate Qi and nourish meridians and collaterals [19].Modern studies have also shown that acupuncture at Jiaji acupoints(Ex-B2) can promote the blood circulation of local spinal nerve roots and mobilize the neurohumoral mechanism to reduce local inflammation for analgesia[20].While most of the related studies focus on the treatment of low back pain, less has been reported about the sciatic nerve symptoms caused by compression of the herniated intervertebral disc.Uncomfortable symptoms such as numbness, tension or tension are often overlooked and significantly more attention is the immediate analgesic effect of treatment.At present, there is no safe and effective treatment for lower limb discomfort.Therefore, this study aimed at the effects of “Tongji” electroacupuncture on patients with lumbar disc herniation in remission stage,exploring the effectiveness and persistence of acupuncture analgesic effect.

Based on the clinical observation,more than 50%of the patients with low back pain are blood stasis syndrome type [21–22].This is because the fundamental contradiction of lumbar intervertebral disk protrusion is a series of symptoms caused by the stress imbalance of two adjacent lumbar vertebrae,intervertebral disc dehydration, degeneration,compression of surrounding tissues and nerves,and the location of the lesion is relatively deep.This study reconfirmed the curative effects of “Tongji”electroacupuncture on patients with blood stasis.

Jiaji acupoints(Ex-B2),also known as Hua Tuo Jiaji acupoints and Tuoji acupoint, is a strange acupoint outside the meridian.The treatment of low back pain by Jiaji acupoints (Ex-B2) was recorded inSu Wen(Plain Questions, one part ofHuang Di Nei Jing, an ancient Chinese medical book that has been treated as the fundamental doctrinal source for Chinese medicine for more than two millennia)· Miao Acupuncture Theory.Acupuncture at Jiaji points(Ex-B2) can enrich the connective tissue such as blood vessels and nerves at acupoints and produce a series of protective effects on lumbar spine.When acupuncturing at 0.1 cm beside the inferior edge of the lumbar spinous process, it can stimulate the superficial branch of the posterior medial branch of the spinal nerve and directly relieve the pain;at 1.6 cm, it can relieve the spasm of the deep muscle,improve the muscle stress and balance the traction on both sides, restore the normal position of the spinal facet joint; at 3.3 cm, it can reach the deep muscle or/and lumbar dorsal muscle and fascia, relieve or reduce the nerve entrapment state [23].Our previous study found that electroacupuncture at Jiaji acupoints(Ex-B2, 3.3 cm beside the posterior midline) could significantly improve clinical symptoms, reduce the score of low back pain, facilitate the recovery of lumbar joint function and improve the ability of daily living.This study also found that on the basis of oral drug therapy, “Tongji” electroacupuncture not only significantly relieves the postoperative pain of the patients, but reduces the content of inflammatory factor IL-6,regulates the secretion of painful substance SP, and inhibits the local immune and inflammatory reaction to a certain extent.After the treatment, no recurrence of pain and numbness symptoms happens,with lasting efficacy and obvious consolidation.

Conclusion

In conclusion, using “Tongji” electroacupuncture combined with oral diclofenac sodium double release enteric-coated capsule in the treatment of lumbar disc herniation has a significant analgesic effect, and improves lumbar function in patients with LDH, which is worthy of promotion for clinical use.However, the mechanism of this therapy in regulating lumbar immune inflammation needs to be further studied.