Effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in knee osteoarthritis patients

CAI Jiangang (蔡建刚), ZHONG Hui (仲慧), WANG Liping (王利平), ZHANG Shuyun (张树芸), MA Yinfei (马银菲)Zhangjiakou First Hospital, Hebei Province, Zhangjiakou 075000, China

Abstract Objective: To observe the effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in patients with knee osteoarthritis (KOA) due to wind-cold-dampness Bi-impediment.Methods: A total of 101 patients with KOA due to wind-cold-dampness Bi-impediment were divided into an acupuncture-medication group and a Chinese medication group using the random number table method.Fifty cases in the Chinese medication group took oral Fang Feng Xi Bi Tang for treatment, and 51 cases in the acupuncturemedication group received additional warming triple needling therapy.The symptom score of traditional Chinese medicine (TCM), inflammatory factor levels, and motor function of the knee joint were compared before and after treatment.The clinical efficacy was also compared between the two groups after treatment.

Keywords: Acupuncture Therapy; Warm Needling Therapy; Triple Needling; Acupuncture Medication Combined;Osteoarthritis, Knee; Inflammation; Randomized Controlled Trial

Knee osteoarthritis (KOA) is a degenerative disease that mainly manifests as swelling and pain in the knee joint.With the progression of the disease, some patients may see their knee joints deformed, which severely affects their daily lives[1].In China, KOA is commonly seen among women aged 40 years and above, and its incidence reaches about 19.2% and increases with age[2].In traditional Chinese medicine(TCM), KOA is classified as bone Bi-impediment syndrome.The deficiency of the liver and kidney and undernourished sinews and bones are mainly involved in the pathogenesis, so the treatment should focus on reinforcing the liver and kidney and strengthening the sinews and bones[3].To interpret it further, the deficiency of healthy Qi is the basic pathogenic factor of developing KOA, and this deficiency causes the body’s susceptibility to wind, cold, and dampness pathogens,thus aggravating the symptoms of KOA[4].Western medicine takes anti-inflammation, easing pain, and protecting cartilage as major approaches to treat KOA,which can mitigate the clinical symptoms but may cause various adverse reactions and relapses after drug withdrawal[5].Warming needling is effective in treating KOA[6].This study observed the effects of warming triple needling plus Chinese medication on inflammatory responses and daily living in KOA patients.

1 Clinical Materials

1.1 Diagnostic criteria

1.1.1 Diagnostic criteria in Western medicine

We consulted the criteria in theGuidelines for Diagnosis and Treatment of Osteoarthritis(2018 Edition)[7]: recurrent knee joint pain in the last month; Xray examination revealed subchondral osteosclerosis or cystic degeneration, joint space narrowing, or osteophyte at the joint periphery; aged 50 or above;morning stiffness no longer than 30 min and bony crepitus or sensation during movements.

1.1.2 Diagnostic criteria in TCM

The diagnosis of bone Bi-impediment of wind-colddampness pattern consulted the criteria in theDiagnosis and Treatment Protocols of Traditional Chinese Medicine for 22 Professionals and 95 Diseases[8].The primary complaints were knee joint swelling, pain,and motor dysfunction.The secondary symptoms included the pain reduced with warmth and worsened with cold, cold sensations in the limbs and fear of cold,swelling joints, a pale tongue body with white coating,and deep tight pulses.

1.2 Inclusion criteria

Those who conformed to the above diagnostic criteria; those who could provide complete medical data; the patient and their families understood this study and offered informed consent.

1.3 Exclusion criteria

Those with significant organ dysfunctions; those with mental disorders or cognitive impairments; those comorbid with other forms of knee joint injuries like fracture or tendon rupture; those with skin infections;those allergic to the medicines used in the trial; those with a previous history of knee surgery or grade Ⅳassessed by the Kellgren-Lawrance (K-L) scale[9].

1.4 Dropout and elimination criteria

Those showing poor compliance and unable to receive treatments on time following the schedule of the trial or receiving treatments from other sources during the study; those having severe complications or adverse events during the study and unable to proceed with the trial; those quit the study on their own; loss to visit on social media or phone.

1.5 Statistical methods

The SPSS version 26.0 software was used to process data.Counting data were expressed as cases or percentages, and between-group comparisons were analyzed using the Chi-square test.The Kolmogorov-Smirnov test proved the normal distribution of the measurement data, which thus were expressed as mean ± standard deviation (±s) and analyzed using thet-test in both intra-group and between-group comparisons.The statistical significance was accepted whenP<0.05.

1.6 General data

This trial was approved by the Ethics Committee of Zhangjiakou First Hospital, Hebei Province (Approval No.2020-0635).We recruited 101 patients who visited the TCM Physiotherapy Department of the hospital between August 2020 and August 2022 for KOA due to wind-cold-dampness Bi-impediment.They were divided into an acupuncture-medication group (51 cases) and a Chinese medication group (50 cases) using the random number table method.The acupuncture-medication group had 3 dropouts during the study: 2 loss to visit and 1 withdrawal.The Chinese medication group had 2 dropouts: 1 poor compliance and 1 loss to visit.Ultimately, 96 cases were included in the outcome analysis, including 48 cases in each group.There were no significant differences in gender, age, disease duration, or K-L grading between the two groups(P>0.05), suggesting that they were comparable.The details are shown in Table 1.The flow chart of this study is shown in Figure 1.

Table 1 Comparison of the general data between the two groups

Figure 1 Flow chart of the study

2 Treatment Methods

2.1 Chinese medication group

Patients in the Chinese medication group received oral administration of Fang Feng Xi Bi Tang.

Prescription:Fang Feng(Radix Saposhnikoviae) 20 g,Gou Ji(Rhizoma Cibotii) 20 g,Du Huo(Radix Angelicae Pubescentis) 15 g,Dang Gui(Radix Angelicae Sinensis)15 g,Zhi Gan Cao(Radix Glycyrrhizae Preparata) 10 g,Wei Ling Xian(Radix Clematidis) 10 g,Chuan Xiong(Rhizoma Chuanxiong) 10 g,Jiang Huang(Rhizoma Curcumae Longae) 10 g,Niu Xi(Radix Cyathulae) 10 g,Xi Xin(Herba Asari) 6 g,Fu Zi(Radix Aconiti Lateralis Praeparata) 5 g, andRu Xiang(Olibanum) 5 g.

Preparation: Took 1 dose daily to cook in water.The decoction was separated into 2 portions to take once in the morning and once at night, 100 mL each time.One week was considered 1 course, and 4 treatment courses were observed.

2.2 Acupuncture-medication group

Patients in the acupuncture-medication group received warming triple needling in addition to the same oral Chinese medication.

Points: Neixiyan (EX-LE4), Zusanli (ST36), Yinlingquan(SP9), and Dubi (ST35) on the affected side.

Operation: The patient took a supine position with a soft cushion under the popliteal fossa of the affected leg, and the knee joint bent by 90°.After the sterilization of the points using 75% alcohol, the physician perpendicularly inserted disposable filiform needles of 0.30 mm in diameter and 40 mm in length into the center of the points 30 mm deep.Then, the physician obliquely inserted two needles 0.5 Cun lateral to the insertion spot on both sides with the needle tip toward the center.When the needling sensation arrived(Deqi), a moxa cone (about 3 g) was affixed to the needle handle and ignited with a piece of cardboard protecting the surrounding skin.Each point was treated with 2 moxa cones, costing about 30 min.Then, the needles were removed.The above treatments were performed once every 2-3 d, 3 times a week for 4 weeks.

3 Outcome Observation

3.1 Outcome measures

3.1.1 TCM symptom score

We consulted theGuiding Principles for Clinical Study of New Chinese Medicines[10]to assess the TCM symptoms before and after treatment.The primary and secondary symptoms were scored based on their severity, respectively.Primary symptoms: free of symptom, 0 points; mild, 2 points; moderate, 4 points;severe, 6 points.Secondary symptoms: free of symptom,0 points; mild, 1 point; moderate, 2 points; severe, 3 points.

3.1.2 Inflammatory factor levels

Fasting venous blood was drawn before and after treatment, 6 mL from each person.The blood was centrifuged for 12 min at 2 500 r/min.The supernatant was then collected and stored at -20 ℃ for later tests.The enzyme-linked immunosorbent assay was used to determine the serum inflammatory factor levels,including interleukin (IL)-6, tumor necrosis factor(TNF)-α, and IL-1β.The kits were purchased from Wuhan MSK Biotechnology, Co., Ltd., China.

3.1.3 Knee joint function

We adopted the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) to evaluate the patient’s knee joint function[11].This scale consists of 3 types of indicators, including 24 items.The maximum score is 96 points.Of these, the knee pain intensity score ranges between 0 and 20 points, the knee joint stiffness score 0-8 points, and the daily functioning difficulty score 0-68 points.A higher WOMAC score indicates a worse condition in KOA.

3.2 Efficacy criteria[12]

Clinical control: The relevant signs and clinical symptoms were basically gone; the TCM symptom score was reduced by at least 95%.

Markedly effective: The relevant signs and clinical symptoms showed significant improvements; the TCM symptom score was reduced by ≥70% but <95%.

Effective: The relevant signs and clinical symptoms improved; the TCM symptom score was reduced by≥30% but <70%.

Invalid: The relevant signs and clinical symptoms showed no improvements or were even worse; the TCM symptom score was reduced by <30%.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The total effective rate was 95.8% in the acupuncture-medication group versus 79.2% in the Chinese medication group, and the between-group difference was statistically significant (P<0.05).The result suggested that the acupuncture-medication group produced more significant efficacy than the Chinese medication group.The details are shown in Table 2.

3.3.2 Comparison of TCM symptom score

There was no significant difference in the TCM symptom score between the two groups before treatment (P>0.05).The TCM symptom score dropped significantly in both groups after the intervention and was lower in the acupuncture-medication group than in the Chinese medication group (P<0.05).The details are displayed in Table 3.

Table 2 Comparison of the clinical efficacy between the two groups Unit: case

Table 3 Comparison of the TCM symptom score ( ±s) Unit: point

Table 3 Comparison of the TCM symptom score ( ±s) Unit: point

Note: TCM=Traditional Chinese medicine.

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 24.32±2.88 6.89±0.84 40.253 <0.001 Chinese medication 48 24.26±2.98 11.02±1.26 28.353 <0.001 t-value 0.100 0.920 P-value 0.920 <0.001

3.3.3 Comparison of inflammatory factor levels

There were no significant differences in the serum levels of IL-6, TNF-α, and IL-1β between the two groups before treatment (P>0.05).The serum levels of IL-6,TNF-α, and IL-1β decreased in both groups after treatment and were lower in the acupuncturemedication group than in the Chinese medication group(P<0.05).The data are detailed in Table 4, Table 5, and Table 6.

3.3.4 Comparison of knee joint function

There were no significant differences in the knee pain intensity, knee stiffness, and daily functioning difficulty scores between the two groups before treatment(P>0.05).The knee pain intensity, knee stiffness, and daily functioning difficulty scores dropped in the two groups after treatment and were lower in the acupuncture-medication group than in the Chinese medication group (P<0.05).See Table 7-Table 9.

Table 4 Comparison of the serum IL-6 level ( ±s) Unit: ng/L

Table 4 Comparison of the serum IL-6 level ( ±s) Unit: ng/L

Note: IL-6=Interleukin-6.

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 33.68±8.23 15.21±7.11 11.766 <0.001 Chinese medication 48 33.75±8.21 25.43±7.97 5.038 <0.001 t-value 0.042 6.519 P-value 0.967 <0.001

Table 5 Comparison of the serum TNF-α level ( ±s) Unit: mg/L

Table 5 Comparison of the serum TNF-α level ( ±s) Unit: mg/L

Note: TNF-α=Tumor necrosis factor-α.

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 0.93±0.23 0.42±0.15 12.868 <0.001 Chinese medication 48 0.91±0.25 0.69±0.18 4.948 <0.001 t-value 0.408 7.984 P-value 0.684 <0.001

Table 6 Comparison of the serum IL-1β level ( ±s) Unit: ng/L

Table 6 Comparison of the serum IL-1β level ( ±s) Unit: ng/L

Note: IL-1β=Interleukin-1β.

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 56.27±9.61 42.13±8.14 7.779 <0.001 Chinese medication 48 56.43±9.58 48.89±8.67 4.043 <0.001 t-value 0.082 4.129 P-value 0.935 <0.001

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 13.21±3.47 7.01±2.43 10.140 <0.001 Chinese medication 48 13.42±3.35 8.79±2.73 7.423 <0.001 t-value 0.302 3.374 P-value 0.764 0.001

Table 7 Comparison of knee pain intensity score ( ±s) Unit: point

Table 7 Comparison of knee pain intensity score ( ±s) Unit: point

Table 8 Comparison of knee joint stiffness score ( ±s) Unit: point

Table 8 Comparison of knee joint stiffness score ( ±s) Unit: point

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 5.08±1.78 1.62±1.31 10.846 <0.001 Chinese medication 48 5.11±1.68 2.79±1.44 7.264 <0.001 t-value 0.085 4.164 P-value 0.933 <0.001

Table 9 Comparison of daily functioning difficulty score ( ±s) Unit: point

Group n Before treatment After treatment t-value P-value Acupuncture-medication 48 40.88±13.22 20.83±8.24 8.917 <0.001 Chinese medication 48 41.02±13.17 25.03±8.76 7.004 <0.001 t-value 0.052 2.420 P-value 0.959 0.017

4 Discussion

KOA mainly manifests as the formation of osteophytes, subchondral bone changes, and cartilage degradation, often accompanied by joint swelling and pain, or even deformity, with a high risk of disability and recurrence.As a result, it significantly affects the patient’s physical and mental health.According to TCM theory, the essential pathogenesis of KOA involves the deficiency of the liver and kidney and the invasion of wind, cold, and dampness pathogens.Hence, the treatment of KOA should focus on reinforcing the liver and kidney and dispelling wind, cold, and dampness.

The study revealed that the TCM symptom score dropped in both groups after the intervention and was lower in the acupuncture-medication group than in the Chinese medication group.Also, the serum IL-6, TNF-α,and IL-1β levels were lower in the acupuncturemedication group than in the Chinese medication group after treatment.These results suggest that warming triple needling plus Fang Feng Xi Bi Tang can improve TCM symptoms and inflammatory responses in KOA patients.The post-treatment changes in IL-6, TNF-α,and IL-1β were similar to those in the studies of MA S Y,et al[13]and ZHOU L L[14].Two aspects contribute to the result.First, Fang Feng Xi Bi Tang can dispel wind, cold,and dampness.In this prescription,Wei Ling Xian,Du Huo, andFang Fengwork to clear wind and dampness and ease the pain.Modern pharmaceutical research discovers thatFangFengcontains prim-Oglucosylcimifugin and pyranocoumarins, which can regulate immune function, reduce inflammation and bacteria, kill pain, and release heat[15].Dang Guicontains polysaccharides that can enhance the activity of immune cells and fortify specific and non-specific immunocompetence[16].Gou JiandJiang Huangcontain protocatechuic acid and curcumin, respectively, which can inhibit inflammatory responses[17-18].Chuan Xiong,Ru Xiang, andJiang Huangact to unblock meridians to stop pain, circulate blood, and dredge collaterals.Niu XiandGou Jican reinforce the liver and kidney to strengthen sinews and bones.Last but not least,Zhi Gan Caoworks to harmonize medicines and tonify Qi of the spleen and stomach.These medicines combine together to form Fang Feng Xi Bi Tang, producing satisfactory efficacy in treating KOA due to wind-colddampness Bi-impediment.Second, of the four points treated with warming triple needling, Yinlingquan (SP9),Zusanli (ST36), and Dubi (ST35) are from either the Spleen Meridian or the Stomach Meridian.The spleen and stomach are the source of generating Qi and blood and are thus called postnatal foundations[19].Warming triple needling at the above three points can activate Qi of the Spleen and Stomach Meridians, regulate Qi and blood, reinforce the spleen and stomach, and eliminate dampness and cold.Neixiyan (EX-LE4) is an extra point often used to treat lower limb diseases as it can circulate blood and cease pain[20].The four points cooperate in circulating blood, unblocking collaterals,and dissipating stasis to stop the pain and dispel wind,cold, and dampness.Warming triple needling plus Fang Feng Xi Bi Tang can reinforce the liver and kidney and eliminate wind, cold, and dampness, treating KOA from both root causes and superficial manifestations.

With the constant progression of the disease, KOA patients may experience joint contracture and motor dysfunction, which significantly affect their daily living[21].This study showed that the knee pain intensity,knee joint stiffness, and daily functioning difficulty scores dropped in both groups after treatment and were markedly lower in the acupuncture-medication group than in the Chinese medication group, and the acupuncture-medication group obtained a higher total effective rate than the Chinese medication group.These results support that warming triple needling plus Fang Feng Xi Bi Tang can produce more significant effects in improving the patient’s joint function and daily functioning and enhancing clinical efficacy than using the Chinese medication alone.

To sum up, warming triple needling combined with Fang Feng Xi Bi Tang can effectively reduce inflammatory responses, ameliorate daily functioning,and improve the quality of life in patients with KOA.However, the design of the study was too elementary,and the sample scale was small.These weaknesses require improvements in subsequent studies.

Conflict of Interest

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

Acknowledgments

This work was supported by the Key Research and Development Program of Zhangjiakou, Hebei Province (张家口市重点研发计划项目, No.2221166D).

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received: 13 June 2023/Accepted: 11 September 2023