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Research Article

2018; 11(4): 145-152

Published online August 1, 2018 https://doi.org/10.1016/j.jams.2018.05.005

Copyright © Medical Association of Pharmacopuncture Institute.

Effect of Auriculotherapy on the Plasma Concentration of Biomarkers in Individuals with Knee Osteoarthritis

Rebeca Graça Costa-Cavalcanti18, Danúbia da Cunha de Sá-Caputo28, Eloá Moreira-Marconi38, Cristiane Ribeiro Küter18, Samuel Brandão-Sobrinho-Neto18, Laisa Liane Paineiras-Domingos48, Marcia Cristina Moura-Fernandes38*, João Marcelo Castelpoggi da Costa5, José Maurício de Moraes Carmo5, José Firmino Nogueira-Neto6, Shyang Chang7, Mario Bernardo-Filho8

1Mestrado Profissional Em Saúde, Medicina Laboratorial e Tecnologia Forense, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
2Faculdade de Fisioterapia, Faculdade Bezerra de Araújo, Campo Grande, RJ, Brazil
3Programa de Pós-Graduação Em Fisiopatologia Clínica e Experimental, Faculdade de Ciências Médicas, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
4Programa de Pós-Graduação Em Ciências Médicas, Faculdade de Ciências Médicas, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
5Departamento de Especialidades Cirúrgicas, Faculdade de Ciências Médicas, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
6Laboratório de Lípides, Faculdade de Ciências Médicas, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
7Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China
8Laboratório de Vibrações Mecânicas e Práticas Integrativas, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Correspondence to:Marcia Cristina Moura-Fernandes

Received: December 26, 2017; Revised: March 30, 2018; Accepted: May 9, 2018

http://creativecommons.org/licenses/by-nc-nd/4.0/

Abstract

Knee osteoarthritis (KOA) is one of the most frequent noncommunicable diseases with pain associated symptoms and affects the musculoskeletal system. Various forms of treatment can be indicated, and nonpharmacological treatment is also an available option for the management of KOA individuals. For instance, auriculotherapy (AT) is one possible procedure associated with the Traditional Chinese Medicine for dealing with KOA. It is believed that the concentration of certain biomarkers could be altered in individuals with KOA after AT. The aim of this study was to evaluate the effect of AT on plasma concentration of biomarkers in KOA individuals. This intervention is a controlled trial. Twenty-one subjects were grouped in two groups and submitted to AT with the stimulation of the Shen Men, kidney, and knee points in the treatment group or different points in the control group, once a week for 5 weeks. Blood was collected before the beginning of protocols and a week after the last session. Kolmogorov–Smirnov and Wilcoxon tests were performed, and a p ≤ 0.05 was considered statistically significant. Hematological parameters did not show any significant variation between the control group and treated group. Concerning the biochemical parameters, a significant reduction of direct bilirubin (from 43.31 ± 22.10 to 21.21 ± 5.30 μmol/L, p = 0.003), aspartate aminotransferase (from 0.48 ± 0.16 to 0.38 ± 0.09 μKat/L, p = 0.010), and triglycerides (from 7.04 ± 2.90 to 5.45 ± 2.57 mmol/L, p = 0.008) in the treated group was obtained. In conclusion, the analysis of results suggests that AT might be a useful intervention for the management of KOA individuals.

Keywords: auriculotherapy, bilirubin, biomarkers, knee osteoarthritis

1. Introduction

Osteoarthritis (OA) is a degenerative joint disease [1] characterized by focal and progressive loss of the hyaline cartilage, associated with bony changes. Usually, it is defined by symptoms such as pain, swelling, and joint stiffness. Radiographs have been used to aid in the diagnosis of the osteoarthritis. Changes, including joint space narrowing, development of osteophytes, and bony sclerosis or a combination of these can be observed in the radiographic images. [2].

The increase of OA world prevalence is related to aging [3]; it affects 13.9% of adults aged 25 years and older and 33.6% of those older than 65 years [4]. Women had higher rates than men, especially those older than 60 years. The knee is the joint in the leg most commonly affected, and a clinical radiographic diagnosis requires (i) the presence of osteophytes, (ii) knee pain, and (iii) age > 50 years, joint stiffness < 30 minutes, or crepitus [5]. Although there are clinical, clinical plus laboratory, and clinical plus radiographic tests, there is no consensus about the best criteria for diagnosing OA in clinical practice.

Knee osteoarthritis (KOA) has a multifactorial etiology, and a cure is not known [6]. The knee pain is recognized as one of the characteristic symptoms that causes limitations in daily activities and is often the main complaint in clinical care [7]. Owing to high probability of unfavorable prognosis, KOA should be diagnosed early and treated with either nonpharmacological or pharmacological procedures [1]; however, the clinical efficiency of agents like analgesic and antiinflammatory is limited, and the adverse effects are unwanted [8, 9].

The main emphasis in KOA management is pain relief and function improvement, with minimal adverse effects. American College of Rheumatology 2012 Recommendations suggest conditionally the use of acupuncture, a technique of Traditional Chinese Medicine. Auriculotherapy (AT) is recommended when the patient with KOA has chronic moderate to severe pain and is a candidate for total knee arthroplasty, but is unwilling to undergo this procedure or the patient has comorbid medical conditions or is taking concomitant medications that lead to a relative or absolute contraindication to surgery or a decision by the surgeon not to recommend the procedure.

AT is a type of nonpharmacological therapy [9, 10], usually performed with needles. It is reported to be effective in the treatment for reducing chronic pain caused by KOA because of its analgesic effect, besides being associated with improved functional mobility and quality of life [8]. AT is achieved by the stimulation of points in a specific anatomical region, in the case of ear. It may be performed, among other methods, with mustard seeds (Semen vaccariae). It may generate effects in specific parts of the body, due to the somatotopic organization of the ear with direct relation to the human body through the branches of pairs of cranial nerves innervating the whole ear. [11].

Concerning the AT treatment, Manheimer et al, 2006 [12] demonstrated that AT therapy using needles seems to be effective for pain relief in cases of KOA. Yeh et al, 2014 [13] demonstrated a reduction in pain intensity and improvement in physical function in adult patients after auricular point acupressure. Moreover, other investigations involving AT have demonstrated beneficial effects in the management of postoperative pain relief due to knee arthroscopy [14]. Santoro et al, 2015 [15] demonstrated an increase in pain tolerability, rather than affecting the minimal pain threshold in healthy individuals. Furthermore, a systematic review [16] of the effect of the AT for pain management concluded that AT may be effective for the treatment of a variety of types of pain, especially postoperative pain.

Alteration in the plasma concentration of some biomarkers because of AT has been reported. Ju et al, 2014 [17] have described that the stimulation in the cavum conchae (region of the ear) may be an effective treatment for patients with type 2 diabetes mellitus. This procedure helps to decrease glycated hemoglobin, blood urea nitrogen, serum creatinine, total cholesterol (TC), and aspartate transaminase. Abdi et al, 2012 [18] have pointed out that the combination of AT plus dietary regulation is effective for weight loss and dyslipidemia, with possible effects on the immunological system.

Here we hypothesized that AT could alter the concentration of biomarkers in individuals with KOA.

The purpose of this study is to evaluate the effect of the AT on the concentration of some biomarkers in the plasma of patients with KOA.

2. Material and methods

2.1. Participants and ethical approach

This intervention is a controlled trial in which the effect the AT on the concentration of blood biomarkers is evaluated in individuals with KOA. It was approved by the Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro Ethics Committee (CAAE 19826413.8.0000.5259). Twenty-three participants diagnosed with KOA were recruited in the Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro. A physician (orthopedist) defined the clinical diagnosis of the individuals with KOA. In addition, patients who participated in the project signed a consent form before any procedure.

2.2. Anthropometric evaluation

The gender, age, height, body mass, and body mass index (BMI) of the individuals accepted in this study were noted. The patients were asked to maintain their usual lifestyle during the period of the intervention.

2.3. Inclusion and exclusion criteria

For this prospective study, the inclusion criteria for the intervention with AT were (i) patients aged above 40 years, (ii) men and women, (iii) with previous clinical diagnosis of KOA, and (iv) signing of an Instrument of Consent.

The exclusion criteria were (i) patients without diagnosis confirmation of KOA, (ii) younger than 40 years, (iii) high levels of blood pressure, ≥160 × 110 mmHg, (iv) severe or disabling medical illness, at the discretion of the investigator, like cardiovascular disease (coronary artery disease or stroke), neurological, musculoskeletal, or rheumatologic disease that do not permit the stimulation with seeds, (v) who refused to sign a consent form of participation in the study, or (vi) who were unable to complete the proposed steps of this research.

2.4. Measures

The participants, for convenience in order which they reached to the laboratory, were alternately allocated into two groups (auriculotherapy group—ATG and control group—CG). For each group, blood samples were collected by venipuncture one day before the beginning of intervention and a week after the last session to obtain a chronic evaluation. All blood samples were drawn in the morning after 12-h overnight fast by a qualified professional of the Hospital Universitário Pedro Ernesto that has the function to drawn blood samples. All participants were under medication indicated by the physician.

Assays were performed with commercially available assay kits and were analyzed on the same day of blood collection at the Laboratory of the Hospital Universitário Pedro Ernest. Specific procedures for each biomarker were followed, as indicated by the manufacturer. To the evaluation of the hematological parameters, the blood was collected in EDTA tubes and was measured by a hematology analyzer (XS—1000i/Sysmex).

A tube with clot activator and gel for serum separation was used to perform serum testing, using an automatic chemistry analyzer (A25/BioSystem) after centrifugation of the blood (2000 rpm, clinical centrifuge, 10 minutes). The biomarkers analyzed were glucose, uric acid, urea, creatinine, total protein, globulin, albumin and bilirubins, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase, gama-glutamil transpeptidase, alkaline phosphatase, C-reactive protein (CRP), plasma triacylglycerols (TG), TC, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), very low-density lipoprotein cholesterol, and calcium.

2.5. Auriculotherapy protocol

The participants received five sessions of either true AT (ATG) or sham AT (CG) at the laboratory once a week (on the same day of the week) for 5 weeks. All the procedures involving the fixation of the adhesive tapes were performed by a specialized professional in Traditional Chinese Medicine, including AT since 2003. Each session of stimulation was 10 minutes in duration. Asepsis of the ear was with 75% alcohol, and it was performed before the procedure. All participants who had adhesive bandages fixed on the ear with or without seeds received instructions to press them three times a day at least. On the night before of next session, the participants were asked to remove the bandage.

The individuals of the CG received pieces of bandages without seed fixed in lobe of the ear points mimicking the seeds with adhesive tape, as shown in Fig. 1A.

Figure 1. A) Tapes without seed (CG) in the lobe of the ears. (B) Seeds at acupoints (ATG). Knee joint is located at the superior crus of the antihelix. Shen Men is located at the bifurcation of the crura of the antihelix. Kidney is lying in the upper part of the cymba conchae.

To verify the effect of AT in KOA patients, acupressure was done with fingers on the knee points, kidney and Shen Men (French School) were each bilaterally stimulated by bandage with two mustard seeds, as shown in Fig. 1B.

2.6. Statistical analysis

Statistical analysis was performed using the software BioEstat 5.0. The normality of continuous variables was assessed using the Kolmogorov–Smirnov test. Data were analyzed comparing the parameters values before and after the protocols with Wilcoxon. The values of the measurements were expressed as mean and standard deviations. A p ≤ 0.05 was considered statistically significant.

3. Results

The participants were 19 females and four males and the age ranged from 50 to 71 years old (62 ± 5.51). Their mean previous BMI (calculated before any protocol procedure) was 32.85 ± 6.47 kg/m2, and they were classified as obese [19]. The BMI was not significantly (p > 0.05) altered just after the intervention. The participants have not reported other diseases besides obesity and KOA.

The flow diagram with the enrollment of the participants is shown in the Fig. 2. In the total of 23 participants, divided to either the CG or ATG, two women (one in each group) concluded the intervention protocol but did not return to the blood exams a week after sessions finished. There were 21 people who completed the study, 17 women and 4 men. No differences were observed between the two groups regarding anthropometric characteristics at baseline or after last session (results not shown).

Figure 2. Flow diagram with the enrollment of the participants.

Table 1 shows the measurements of hematological parameters to both groups (CG and ATG), before and after the correspondent protocol. It was observed that in the CG, as in the ATG, the concentrations of the plasma biomarkers were not altered on the period of time of the study. No significant result, but with an important alteration, was found in the percentage of the basophils due to the treatment of the AT.

ATG = auriculotherapy group; CG = control group; KOA = knee osteoarthritis; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; RDW = red cell distribution width..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Hematological parameters in patients with KOA before and after the protocols..

Hematological parametersCG (n = 11)ATG (n = 10)


BeforeAfterpBeforeAfterp
Red blood cell (1012/L)4.69 ± 0.374.63 ± 0.430.2244.60 ± 0.644.54 ± 0.710.220
Hemoglobin (g/dL)12.94 ± 0.6912.76 ± 0.920.16613.05 ± 1.1212.09 ± 1.280.297
Hematocrit (%)40.17 ± 2.1639.51 ± 2.260.17940.16 ± 3.4840.0 ± 4.300.287
MCH (pg)27.72 ± 2.3327.67 ± 2.300.37928.53 ± 2.0728.88 ± 2.500.104
MCV (fL)86.03 ± 7.2085.74 ± 6.660.41287.83 ± 5.8788.7 ± 6.370.203
MCHC (g/L)32.20 ± 1.0032.27 ± 1.050.48232.50 ± 0.7432.52 ± 0.790.429
RDW (%)14.13 ± 0.7813.91 ± 1.230.17914.08 ± 1.0614.46 ± 0.870.061
White blood cell (109/L)5.81 ± 1.576.02 ± 2.080.4296.06 ± 2.175.97 ± 1.990.339
Neutrophils (%)57.41 ± 7.8554.71 ± 11.090.06555.48 ± 7.8355.80 ± 10.250.479
Basophils (%)0.31 ± 0.180.24 ± 0.270.1660.60 ± 0.830.20 ± 0.220.181
Eosinophils (%)3.18 ± 2.513.90 ± 3.440.1204.61 ± 5.624.31 ± 4.750.406
Lymphocyte (%)31.79 ± 6.1433.68 ± 9.140.10631.35 ± 6.2131.32 ± 8.860.399
Monocytes (%)7.38 ± 2.197.35 ± 2.550.4597.96 ± 1.638.37 ± 1.950.220
Platelets (109/L)252.54 ± 45.51256.90 ± 49.030.399272.60 ± 72.59260.80 ± 66.210.057

ATG = auriculotherapy group; CG = control group; KOA = knee osteoarthritis; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; RDW = red cell distribution width..



The measurements of biochemical biomarkers on the plasma of participants with KOA, before and after protocols, are shown in the Table 2. Regarding the biomarker of renal function, there was no significant alteration after the protocols in both groups. The dosages of total protein and protein fractions plasma, similarly, did not appear to be influenced by the stimulation of points of the ear selected in this research.

AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; GGT = gama-glutamil transpeptidase; CK = creatine kinase; CRP = C-reactive protein; KOA = knee osteoarthritis; TC = total cholesterol; HDLC = high-density lipoprotein cholesterol; LDLC = low-density lipoprotein cholesterol: VLDLC = very-low-density lipoprotein cholesterol; TG = plasma triglycerides. *Significant difference..

&md=tbl&idx=2' data-target="#file-modal"">Table 2

Biochemical parameters in patients with KOA before and after protocols..

Biochemical parametersCG (n = 11)ATG (n = 10)


BeforeAfterpBeforeAfterp
Glucose (mmol/L)6.04 ± 2.065.97 ± 1.130.4795.50 ± 0.935.66 ± 0.920.257
Urea (mmol/L)1.82 ± 0.461.75 ± 0.600.2531.86 ± 0.751.82 ± 0.780.479
Creatinine (μmol/L)75.53 ± 18.2780.36 ± 11.490.18791.93 ± 28.2289.28 ± 18.560.379
Uric acid (mmol/L)0.27 ± 0.060.26 ± 0.070.4290.32 ± 0.110.33 ± 0.130.253
Total protein (g/L)62.09 ± 4.8265.72 ± 8.670.17568.80 ± 14.2066.30 ± 7.000.383
Albumin (g/L)39.09 ± 3.1739.90 ± 2.870.23841.00 ± 6.7039.40 ± 3.700.276
Globulin (g/L)23.00 ± 3.7425.81 ± 8.550.32327.80 ± 8.7026.90 ± 6.100.360
Bilirubin (μmol/L)69.91 ± 19.9482.77 ± 27.740.06192.82 ± 39.7861.88 ± 17.680.005*
Direct bilirubin (μmol/L)34.55 ± 25.1435.36 ± 19.360.28743.31 ± 22.1021.21 ± 5.300.003*
Indirect bilirubin (μmol/L)35.36 ± 13.1047.41 ± 17.800.13149.50 ± 30.9440.66 ± 14.140.131
AST (μKat/L)0.38 ± 0.090.42 ± 0.110.1300.48 ± 0.160.38 ± 0.090.010*
ALT (μKat/L)0.31 ± 0.080.35 ± 0.090.1060.43 ± 0.140.34 ± 0.080.084
ALP (μKat/L)1.12 ± 0.361.02 ± 0.310.2221.21 ± 0.441.11 ± 0.320.360
GGT (μKat/L)0.58 ± 0.390.54 ± 0.400.4290.71 ± 0.770.71 ± 0.940.459
CK (μKat/L)2.62 ± 1.793.00 ± 1.840.2383.50 ± 2.393.14 ± 2.500.101
Calcium (mmol/L)0.55 ± 0.110.55 ± 0.070.3120.55 ± 0.090.53 ± 0.0050.317
CRP (mg/L)4.60 ± 3.684.45 ± 3.540.3774.00 ± 3.94.70 ± 6.900.341
TC (mmol/L)11.52 ± 2.1412.07 ± 3.640.39413.16 ± 3.7112.17 ± 1.360.379
HDLC (mmol/L)3.44 ± 0.933.34 ± 0.970.2384.39 ± 1.564.45 ± 1.620.399
LDLC (mmol/L)6.74 ± 1.747.33 ± 3.570.4647.36 ± 3.416.62 ± 1.680.399
VLDLC (mmol/L)1.32 ± 0.371.39 ± 0.440.3611.41 ± 0.571.08 ± 0.520.007*
TG (mmol/L)6.64 ± 1.836.97 ± 2.180.3947.04 ± 2.905.45 ± 2.570.008*

AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; GGT = gama-glutamil transpeptidase; CK = creatine kinase; CRP = C-reactive protein; KOA = knee osteoarthritis; TC = total cholesterol; HDLC = high-density lipoprotein cholesterol; LDLC = low-density lipoprotein cholesterol: VLDLC = very-low-density lipoprotein cholesterol; TG = plasma triglycerides. *Significant difference..



Regarding some liver function parameters, while the direct bilirubin and AST did not present any significant alteration in CG (p = 0.287 and p = 0.130, respectively), they showed a significant reduction in ATG after the AT protocol (p = 0.003 and p = 0.010, respectively).

With regard to blood lipid profile, in the group treated with AT, TG decreased from 7.04 ± 2.90 to 5.45 ± 2.57 mmol/L (p = 0.008) and very low-density lipoprotein cholesterol decreased from 1.41 ± 0.57 mmol/L to 1.08 ± 0.52 mmol/L (p = 0.007) after five sessions of AT. However, these changes were not found in the CG. The concentrations of TC, HDLC, and LDLC did not change significantly, nor were CRP, calcium, and CK modified.

4. Discussion

Although the participants of this study were obese, in general, the evaluations and discussions of the effect of the AT were related to the KOA on the concentration of plasma biomarkers. Other authors have evaluated the effect of AT on plasma biomarkers, such as Sampaio-Filho et al [29] who evaluated the effect of low-level laser at AT points to reduce postoperative pain in inferior third molar surgery. To the best of our knowledge and considering the publications of the PubMed databank, this is the first study that investigates the AT effect on the plasma concentration in KOA individuals.

Suen et al [20] described that AT can be applied to elders with KOA as a treatment with effect in terms of pain relief, ambulation status, and range of movement of the knees during flexion and extension. It has been shown that AT it is not an invasive therapy, and it could be an interesting tool for the management of these individuals. The patients were asked to maintain their normal lifestyle during the period of time of the intervention, and their antropometric parameters (height, body mass, and BMI) were the same before and just after the 5 weeks procedure. Moreover, it is important to consider that the patients of both groups in the current study had an elevated concentration of the level of bilirubin, TC, LDLC, and triglycerides before the intervention. Following the statements of the American College of Rheumatology 2012 Recommendations, these altered concentrations of the level of the referred biomarkers might also justify the use of a technique of the Traditional Chinese Medicine in the KOA population that was submitted to the AT. Moreover, the increased concentration of bilirubin could be associated with liver disease [30].

The present study aimed to investigate the effects of AT on blood profile of KOA patients, men and women, aged above 40 years. The obtained results in KOA patients showed that AT caused a greater decrease in direct bilirubin, AST, and TG (Table 2), although the hematological parameters were not altered (Table 1).

Although CRP is highly associated with KOA [21] as a measure of an acute phase response and inflammation, the participants in this research started the procedure without elevated concentrations of this biomarker in the blood. After 5 weeks, in both groups, controlled and treated ones, there was no statistically significant change in blood concentration. These findings are consistent with those described by Abdi et al [18] who used seeds in points of overweight and obese subjects and measured CRP before and after 12 weeks without finding significant changes between treated and CGs.

It could be important to consider the role of the calcium signal in the chondrocyte mechanobiology [22]. Moreover, periarticular muscles can contribute to joint stability, fundamental for patients suffering with KOA, and the fact that the muscle damage is absent, considering the biomarker CK, it is important to monitor the treatment with AT [23]. In Table 2 we show that AT (at the knee, Shen Men, and kidney points) did not alter the concentration of CK and calcium in the current study.

Teng et al [24] have evaluated the effect of the different types of Traditional Chinese Medicine related to liver function and have observed that a couple of therapies could interfere in zinc and magnesium concentration. Beyond the trace elements, the liver function could be evaluated by biomarkers. In our current research the concentration of AST and bilirubin were reduced in blood (Table 2). This fact has demonstrated that bilateral AT probably does not promote liver alteration in KOA patients after five sessions of therapy.

Similar to our data (Table 2), the reduction in AST values due to the intervention with AT also was described by Ju et al [17]. They have proposed a treatment with auricular electrical stimulator in the cavum choncha for 30 min, once daily for three consecutive months, that was effective in decreasing the plasma levels of serum creatinine and total cholesterol. Moreover, considering the muscle activity, Colombini et al [32] have reported that the increased activity of AST, CK, and lactate dehydrogenase indicates a progressive increase in muscular effort, possibly associated with a certain degree of muscular damage [31]. The increased activity of AST, CK, and LDH, as already reported [32], marks a progressively increased muscular effort, possibly associated with a certain degree of muscular damage [31].

The evaluation of the lipid profile could be an important tool in the care of KOA patients. Ju et al [17] have observed, in patients with type 2 diabetes, a reduction in total cholesterol values in blood. Abid et al [18] have observed, in obese individuals, no significant changes comparing control and case groups. In the current study, a decrease of TG and VLDL concentration in KOA patients submitted to bilateral AT was found (Table 2). TG is directly related to visceral obesity, and more and more evidence suggests that the visceral obesity is associated with an inflammatory state in a certain degree, including OA. Although we observed a small, but not significant, increase of HDLC after AT protocol, it is important to note that in the CG there was a reduction in the concentration of this biomarker. Considering that HDLC plasma concentration can be increased by the use of medications, primarily statin [25] and lately nicotinic acid and fibrates [26], and maybe AT could be a nonpharmacological treatment that promotes this fact. On the other hand, the alterations in these biomarkers are interesting because reduction of anthropometric factors of these obese patients after treatment protocol was not observed.

Abdi et al [18] have also reported that AT plus diet have immunomodulatory effects on the immune system by regulation of the levels of antibodies. Although our data did not show any significant change in immune cells, an important reduction of the percentage of the basophils due to the treatment of the AT was observed. This could be interesting for the treatment of individuals with KOA. According to the findings of Tang et al [27], these cells may be affecting the T helper cells (Th1/Th2) balance in rheumatoid arthritis, another joint disease.

Latini et al [28] suggest the use of serum creatinine as one of standard tools for recognizing changes in renal function. In this current study, the stimulation of the kidney point to treat KOA patients did not significantly alter the plasma concentration of creatinine, uric acid, urea, beyond glucose, and proteins.

There are some limitations in the study, such as the small number of participants, selection of only three points in the ear, and the reduced time of the intervention.

5. Conclusion

Important effects due to the 5 weeks AT treatment of patients with KOA were observed. A decrease in the concentration of some blood biomarkers, such as total and direct bilirubin, triglycerides, and AST, is relevant to the studied population that, besides the presence of KOA, was obese. Furthermore, hematological parameters were not modified. In addition, the findings of this study may stimulate further investigations about the use of AT to the management of KOA individuals.

Acknowledgment

The authors thank the FAPERJ and CNPq for the financial support. They also thank Joel Christopher Creed for a revision of the English language.

Declaration


Ethics approval and consent to participate: This investigation was approved by the Ethics Committee of the Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro (CAAE 19826413.8.0000.5259).

Consent for publication


Not applicable.

Availability of data and materials


The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Disclosure statement


The authors declare that they have no competing interests.

Funding


FAPERJ and CNPq funded this study.

Authors' contributions


RGCC collected, analyzed, and interpreted the blood results, welcomed the patient, presented the research to them, collaborated with the design of the research, and was a major contributor in writing the manuscript. DCSC collaborated with the design of the research, applied auriculotherapy, and accompanied the patients during their stay in the laboratory. EMM, CRK, SBSN, MCMF, and LLPD applied auriculotherapy and accompanied the patients during their stay in the laboratory. JMMC and JMCC diagnosed and indicated the patient to participate in the research. JFNN coordinated the blood evaluation. SC and MBF coordinated the research and designed the research. All authors read and approved the final manuscript.

Fig 1.

Figure 1.A) Tapes without seed (CG) in the lobe of the ears. (B) Seeds at acupoints (ATG). Knee joint is located at the superior crus of the antihelix. Shen Men is located at the bifurcation of the crura of the antihelix. Kidney is lying in the upper part of the cymba conchae.
Journal of Acupuncture and Meridian Studies 2018; 11: 145-152https://doi.org/10.1016/j.jams.2018.05.005

Fig 2.

Figure 2.Flow diagram with the enrollment of the participants.
Journal of Acupuncture and Meridian Studies 2018; 11: 145-152https://doi.org/10.1016/j.jams.2018.05.005

Table 1 . Hematological parameters in patients with KOA before and after the protocols..

Hematological parametersCG (n = 11)ATG (n = 10)


BeforeAfterpBeforeAfterp
Red blood cell (1012/L)4.69 ± 0.374.63 ± 0.430.2244.60 ± 0.644.54 ± 0.710.220
Hemoglobin (g/dL)12.94 ± 0.6912.76 ± 0.920.16613.05 ± 1.1212.09 ± 1.280.297
Hematocrit (%)40.17 ± 2.1639.51 ± 2.260.17940.16 ± 3.4840.0 ± 4.300.287
MCH (pg)27.72 ± 2.3327.67 ± 2.300.37928.53 ± 2.0728.88 ± 2.500.104
MCV (fL)86.03 ± 7.2085.74 ± 6.660.41287.83 ± 5.8788.7 ± 6.370.203
MCHC (g/L)32.20 ± 1.0032.27 ± 1.050.48232.50 ± 0.7432.52 ± 0.790.429
RDW (%)14.13 ± 0.7813.91 ± 1.230.17914.08 ± 1.0614.46 ± 0.870.061
White blood cell (109/L)5.81 ± 1.576.02 ± 2.080.4296.06 ± 2.175.97 ± 1.990.339
Neutrophils (%)57.41 ± 7.8554.71 ± 11.090.06555.48 ± 7.8355.80 ± 10.250.479
Basophils (%)0.31 ± 0.180.24 ± 0.270.1660.60 ± 0.830.20 ± 0.220.181
Eosinophils (%)3.18 ± 2.513.90 ± 3.440.1204.61 ± 5.624.31 ± 4.750.406
Lymphocyte (%)31.79 ± 6.1433.68 ± 9.140.10631.35 ± 6.2131.32 ± 8.860.399
Monocytes (%)7.38 ± 2.197.35 ± 2.550.4597.96 ± 1.638.37 ± 1.950.220
Platelets (109/L)252.54 ± 45.51256.90 ± 49.030.399272.60 ± 72.59260.80 ± 66.210.057

ATG = auriculotherapy group; CG = control group; KOA = knee osteoarthritis; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; RDW = red cell distribution width..


Table 2 . Biochemical parameters in patients with KOA before and after protocols..

Biochemical parametersCG (n = 11)ATG (n = 10)


BeforeAfterpBeforeAfterp
Glucose (mmol/L)6.04 ± 2.065.97 ± 1.130.4795.50 ± 0.935.66 ± 0.920.257
Urea (mmol/L)1.82 ± 0.461.75 ± 0.600.2531.86 ± 0.751.82 ± 0.780.479
Creatinine (μmol/L)75.53 ± 18.2780.36 ± 11.490.18791.93 ± 28.2289.28 ± 18.560.379
Uric acid (mmol/L)0.27 ± 0.060.26 ± 0.070.4290.32 ± 0.110.33 ± 0.130.253
Total protein (g/L)62.09 ± 4.8265.72 ± 8.670.17568.80 ± 14.2066.30 ± 7.000.383
Albumin (g/L)39.09 ± 3.1739.90 ± 2.870.23841.00 ± 6.7039.40 ± 3.700.276
Globulin (g/L)23.00 ± 3.7425.81 ± 8.550.32327.80 ± 8.7026.90 ± 6.100.360
Bilirubin (μmol/L)69.91 ± 19.9482.77 ± 27.740.06192.82 ± 39.7861.88 ± 17.680.005*
Direct bilirubin (μmol/L)34.55 ± 25.1435.36 ± 19.360.28743.31 ± 22.1021.21 ± 5.300.003*
Indirect bilirubin (μmol/L)35.36 ± 13.1047.41 ± 17.800.13149.50 ± 30.9440.66 ± 14.140.131
AST (μKat/L)0.38 ± 0.090.42 ± 0.110.1300.48 ± 0.160.38 ± 0.090.010*
ALT (μKat/L)0.31 ± 0.080.35 ± 0.090.1060.43 ± 0.140.34 ± 0.080.084
ALP (μKat/L)1.12 ± 0.361.02 ± 0.310.2221.21 ± 0.441.11 ± 0.320.360
GGT (μKat/L)0.58 ± 0.390.54 ± 0.400.4290.71 ± 0.770.71 ± 0.940.459
CK (μKat/L)2.62 ± 1.793.00 ± 1.840.2383.50 ± 2.393.14 ± 2.500.101
Calcium (mmol/L)0.55 ± 0.110.55 ± 0.070.3120.55 ± 0.090.53 ± 0.0050.317
CRP (mg/L)4.60 ± 3.684.45 ± 3.540.3774.00 ± 3.94.70 ± 6.900.341
TC (mmol/L)11.52 ± 2.1412.07 ± 3.640.39413.16 ± 3.7112.17 ± 1.360.379
HDLC (mmol/L)3.44 ± 0.933.34 ± 0.970.2384.39 ± 1.564.45 ± 1.620.399
LDLC (mmol/L)6.74 ± 1.747.33 ± 3.570.4647.36 ± 3.416.62 ± 1.680.399
VLDLC (mmol/L)1.32 ± 0.371.39 ± 0.440.3611.41 ± 0.571.08 ± 0.520.007*
TG (mmol/L)6.64 ± 1.836.97 ± 2.180.3947.04 ± 2.905.45 ± 2.570.008*

AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; GGT = gama-glutamil transpeptidase; CK = creatine kinase; CRP = C-reactive protein; KOA = knee osteoarthritis; TC = total cholesterol; HDLC = high-density lipoprotein cholesterol; LDLC = low-density lipoprotein cholesterol: VLDLC = very-low-density lipoprotein cholesterol; TG = plasma triglycerides. *Significant difference..


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