Diagnosis and Objective Pain Assessment of Traditional Chinese Medicine May Be Useful to Demonstrate Specific Effects of Acupuncture in Low Back Pain: A Prospective, Randomized, Controlled and Single Blinded Pre-study

Susana Seca, Paula Capelo, Thomas Efferth, Christoph Alexander Doenitz, Sven Schroeder, Ana Anjos, Jorge Machado, Henry Johannes Greten,

1 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

2 Heidelberg School of Chinese Medicine, Heidelberg, Germany

3 University Hospital Center of Coimbra, Coimbra, Portugal

4 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany

5 HanseMerkur Center for Traditional Chinese Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

6 Porto Biomechanics Laboratory (LABIOMEP), University of Porto, , Portugal

7 German Society of Traditional Chinese Medicine, Heidelberg, Germany

Diagnosis and Objective Pain Assessment of Traditional Chinese Medicine May Be Useful to Demonstrate Specific Effects of Acupuncture in Low Back Pain: A Prospective, Randomized, Controlled and Single Blinded Pre-study

Susana Seca1,2, Paula Capelo3, Thomas Efferth4, Christoph Alexander Doenitz1,2, Sven Schroeder1,5, Ana Anjos1,2, Jorge Machado1,6, Henry Johannes Greten1,2,7

1 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

2 Heidelberg School of Chinese Medicine, Heidelberg, Germany

3 University Hospital Center of Coimbra, Coimbra, Portugal

4 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany

5 HanseMerkur Center for Traditional Chinese Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

6 Porto Biomechanics Laboratory (LABIOMEP), University of Porto, , Portugal

7 German Society of Traditional Chinese Medicine, Heidelberg, Germany

Objective: To prove specific effects of acupuncture on chronic pain. It was speculated that the potential specific effectiveness of acupuncture could be better shown in more properly designed studies. Therefore, diagnoses of both Western medicine and traditional Chinese medicine (TCM) were used as inclusion criteria to allocate acupoints more precisely to the complaints of the patients. Secondly, objectively measurable parameters of pain relief in addition to usual Visual Analogue Scale (VAS) were chosen to quantify the effects of acupuncture.

Methods: The study was prospective, randomized, controlled and single-blinded. Eighteen patients with chronic back pain and TCM diagnosis of a Taiyang/Yangmingsyndrome received one single session of acupuncture chosen according to TCM diagnosis or acupuncture on points outside the meridian system (controls). We evaluated pain via VAS and increased mobility via inclinometry of the back.

Results: Although the sample size was small, there was a statistically significant improvement in pain and mobility in the intervention group (n=13), but not in the control group (n=5). The calculated sample size adequate power was lower for inclinometry than for VAS, indicating that VAS is less probable to discriminate acupuncture effects.

Conclusion: Objectively measurable physical parameters such as the angle of flexion before and after acupuncture (inclinometry) may be more suitable to measure pain relief than subjective assessment by VAS in acupuncture studies. TCM diagnosis may be a helpful inclusion criterion in studies on acupuncture, so as to potentially allocate interventions better to the complaints of patients.

Low Back Pain; Traditional Chinese Medicine; Acupuncture Therapy; Sham Acupuncture; Randomized Controlled Trial

Chronic lower back pain is defined as back pain lasting more than three months[1]. It represents a common clinical syndrome corresponding to an enormous potential for suffering and disability, a problem with broad consequences for the personal, family work level on an epidemic scale[2-3]. Back pain has become one of the most frequent reasons for people to seek health care leading also to considerable economic costs[4].

The effectiveness of acupuncture in chronic back pain is not unequivocally accepted in the literature[5-6]. In the German acupuncture trials (GERAC), the effectiveness of acupuncture was assessed 1.7 times as potent as the standard therapy according to the guidelines with medication and physiotherapy. However, there were no specific effects of acupoints[7-8]. This study and meta-analyses of similar trials raise the question, why the specificity of acupuncture effects is that difficult to assess in a clinical context, though they have been repeatedly shown under experimental conditions.

This study aims to investigate whether specific effects may be more easily shown if pain assessment could be made in terms of measurable physical parameters instead of subjective scores like Visual Analogue Scale (VAS) only. Furthermore, we hypothesized that the traditional Chinese medicine (TCM) diagnosis can nowadays be understood as a vegetative functional status[9-11].

On the basis of this hypothesis, outcome of acupuncture as a reflex therapy would depend on allocation of points to this status (TCM diagnosis). Therefore, we set TCM diagnosis as an inclusion criterion when recruiting the patients to ① homogenize both intervention and control group on a functional level and ② allocate the acupoint concept to patients, who may exactly need the treatment strategy applied.

1 Materials and Methods

The study design was preliminary, prospective, randomized, controlled and single-blinded. The study was carried out according to the guidelines of the Helsinki protocol and approved by the respective ethical commission.

1.1 Inclusion criteria

Unspecific lower back pain for more than three months; major impairment by flexion; TCM diagnosis of a Taiyang/Yangming syndrome as defined in the Shang Han Lun (Treatise on Cold Damage) and as more closely defined by the Heidelberg model of TCM[12-14]; written consent; age ＞18 years; currently no other therapy such as non-steroidal antirheumatic drugs (NSARDs).

1.2 Exclusion criteria

Specific causes for low back pain; contraindications to acupuncture; pregnancy or lactating; major neurological or psychiatric disorders; known autoimmune or inflammatory disease; history of substance abuse; receiving or applying for payments due to handicap or disability; prior acupuncture treatment.

1.3 Recruitment

Patients were recruited from the Pain Consultation Unit of the University Hospitals of Coimbra, Portugal, after written consent. Eighteen individuals were randomly allocated to the intervention group (n=13) or the control group (n=5). The intervention group received eleven needles on acupoints specific to the Chinese diagnosis (Yangming), whereas the control group received eleven needles on unspecific skin areas located outside of meridian region using the same insertion depth, stimulation and gauge.

Pain was assessed in all participants both before and 10 min after treatment using a VAS. In addition, we assessed an objective target parameter that may serve as an objectively measurable indicator of pain reduction. For this purpose, the angle between the trunk and leg was determined using a goniometer (inclinometry), an objective measurement parameter. A decrease in this angle of inclination corresponds to increased ability to bend forwards and was interpreted as a functional improvement of the back by pain relief.

Statistical analysis was carried out with SPSS 17 software (Dynelytics AG, Zurich, Switzerland). Wilcoxon test was used to assess for significant intra-group differences between baseline and after treatment. Mann-Whitney U test was applied to assess for significant intergroup differences between intervention and control. By the use of Receiver Operating Characteristics (ROC) analysis, the effect sizes for the respective Mann-Whitney U group comparison for the VAS and inclination angle were calculated. Sample size and power calculations were performed by using nQuery Advisor Software version 7.0 (Statistical Solutions Ltd., Cork, Ireland).

We chose to present the results in boxplots. The box itself is limited by the lower and upper quartile, thus indicating the value of the middle 50% of the data. The bold line inside the box is the median. The antennas display the 95% confidence interval.

2 Results

A total of 18 patients participated, 13 in the intervention group and five in the control group. The average age was lower in the intervention group (i=45.3±13.6 versus c=60.6±11.5).

Fig.1 and Fig.2 depict the mean level of pain and mean angle of inclination (flexion) for both groups before and after the intervention.

For the control group, there was only a line and a star in measurement before acupuncture (Fig.1). The line represents the median (four out of five participants had VAS 5), the star indicated the single outlier at VAS 7.

The pain level decreased significantly to a level of less than half in the intervention group (4.4±2.0 to 2.1±1.7; P=0.002). In the control group, the reduction was less marked and not significant (5.4±0.9 to 4.2±1.6; P=0.109).

Fig.1 Comparison of pain assessment

Fig.2 Comparison of inclinometry

The angle of inclination significantly improved in the intervention group by 9.31° (122.46±8.80 to 113.15±9.30; P=0.001). In the control group, the reduction was not statistically significant at only 1.60° (118.40±13.83 to 116.80±10.94; P=0.588).

The differences between the groups were not significant (Pain: P=0.143; Inclination: P=0.075).

The Mann-Whitney U test effect size, given by the area under the ROC curve, reflected the probability that for two randomly chosen individuals from the intervention group and control group, the individuals of the intervention group show higher negative change in VAS and inclination angle respectively, compared to the individuals of the control group. For VAS, the effect size revealed to be P=0.738 (G1＜G2), which was slightly smaller compared to the effect size calculated for the inclination angle with P=0.777 (G1＜G2).

Post-hoc sample size calculations revealed that a group sample size of 12 patients for VAS and a group sample size of 9 patients for inclination would have been necessary in order to achieve a significant test result (P＜0.05) with a two-sided Mann-Whitney U test at the actual observed effect sizes. The lack of statistical significance in the inclination comparison (total sample size was 18 as minimal required) was due to the fact that the group sample sizes were not balanced [n=5 (control) vs. n=13 (intervention)].

In order to achieve sufficient power (80%) in prospective studies assuming the same effect sizes as observed with equally sized comparison groups, total sample sizes of 48 patients for VAS and 36 patients for inclination would be needed.

3 Discussion

These results highlight interesting aspects and outcomes of the study.

3.1 Potential role of the TCM diagnosis

After acupuncture, both groups showed amelioration of pain and improvement of mobility. This improvement was only statistically significant in the intervention group. A specific effect of acupuncture was not even shown using meta-analyses with approximately 20 000 patients included. To the best of our knowledge, we cannot see that a well-defined TCM diagnosis was used as the basis of recruitment and point selection in the studies previously examined by Vickers, et al[15]or in the recent review of Linde, et al[16]. These reviews suggested that the effects of acupuncture may be unspecific, which evoked a highly emotional dispute on acupuncture among physicians and within the public.

We interpret our data as a hint that it may be useful to take TCM diagnosis as an inclusion criterion. This seems to be explainable as TCM diagnosis is currently better understood. TCM is now interpreted as a model of vegetative system biology[17]and the diagnosis as vegetative functional state which serves to select reflex points (acupoints). If there was a specific effect of acupuncture, and if our preliminary results could be generalized, this effect might potentially be seen in much smaller sample sizes if TCM diagnosis is set as an inclusion criterion for recruitment and serves as the basis of point selection.

The difference between the two groups was not statistically significant, which may be an effect of the small sample size. Therefore, larger trials in the range of approximate 50/50 patients should be undertaken on the basis of the design here.

Double blinding of acupuncture is possible as earlier shown by our group[18]. Double blinding should be additionally used to exclude suggestive or placebo effects as a possible cause of unspecific acupuncture effects.

3.2 Role of the type of pain assessment

The change of angle of inclination (inclinometry) seems to be a better candidate parameter for a statistical significance as the P-value was closer to reaching significance. Sample sizes such as more than 36 and higher are suggested for adequately powered future studies. This sample size is smaller than that calculated for VAS (48). This suggests that inclinometry may discriminate potential specific effects of acupuncture effects much better than VAS, and about one third less of patients are needed to show significant effects.

VAS and also other scores of subjective sensations and perceptions are widely used for pain assessment. We hypothesized that these parameters may be more inviting to include and detect personal expectations of the patients than the relatively sober assessment of the angle of movements.

The relative lack of discriminative properties of VAS and other scores may have been a possible factor which may have contributed to the poor results analyzed by the reviews quoted above.

4 Conclusion

The overall of clinical trials on acupuncture in chronic pain was interpreted in recent meta-analyses and reviews as acupuncture having a pain relieving effect, which may most possibly be unspecific[19].

However, numerous trials in animals and man have shown under experimental conditions that specific effects of acupuncture exist[20-39]. We hypothesize that there may a specific acupuncture effect on chronic pain too, but more appropriate study designs have to be developed to show these acupoint-dependent effects in nonclinical scenarios. This study suggests that the way to objective study designs may require ① the assessment of the functional state prior to invention by correct TCM diagnosis or other methodologies, and ②the proper assessment tools such as objectively measurable parameters in addition to VAS.

Furthermore, already existing double blinding assays should be combined with these requirements to undertake the first prospective, randomized, controlled clinical trial in chronic back pain to be double blinded.

5 Declaration

The authors hereby certify that there is no actual or potential conflict of interest in relation to this article.

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R246.2

A

Date: January 8, 2013

Author: Susana Seca

Henry Johannes Greten, M.D.

E-mail: heidelbergschool@aol.com