Observation of pain-sensitive points in patients with knee osteoarthritis: A pilot study

Accepted Manuscript Title: Observation of Pain-Sensitive Points in Patients with Knee Osteoarthritis: A Pilot Study Authors: Ya-Nan Luo, Yu-Mei Zhou, Xu Zhong, Ling Zhao, Qian-Hua Zheng, Hui Zheng, Li Tang, Peng-Li Jia, Qiang Wu, Chen Huang, Ying Li, Fan-Rong Liang PII: DOI: Reference:

S1876-3820(18)30336-6 https://doi.org/10.1016/j.eujim.2018.06.006 EUJIM 811

To appear in: Received date: Revised date: Accepted date:

24-3-2018 13-6-2018 13-6-2018

Please cite this article as: Luo Y-Nan, Zhou Y-Mei, Zhong X, Zhao L, Zheng Q-Hua, Zheng H, Tang L, Jia P-Li, Wu Q, Huang C, Li Y, Liang F-Rong, Observation of PainSensitive Points in Patients with Knee Osteoarthritis: A Pilot Study, European Journal of Integrative Medicine (2018), https://doi.org/10.1016/j.eujim.2018.06.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Observation of Pain-Sensitive Points in Patients with Knee Osteoarthritis: A Pilot Study

Ya-Nan Luo a,1, Yu-Mei Zhou a,1, Xu Zhong a, Ling Zhao a, Qian-Hua Zheng

a,*

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, Hui Zheng a, Li Tang b, Peng-Li Jia b, Qiang Wu a, Chen Huang a, Ying Li , Fan-Rong Liang a,**

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a

Acupuncture and Tuina School, Chengdu University of Traditional Chinese

Chinese Evidence-based Medicine Center, West China Hospital, Sichuan

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b

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Medicine, Chengdu, Sichuan , China

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University, Chengdu ,Sichuan, China

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ABSTRACT

Introduction: The sensitive points are important points for acupuncture in traditional Chinese medicine. Previous studies have focused mainly on

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heat-sensitive points in patients with knee osteoarthritis (KOA). The aim of this

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study was to observe the distribution of pain-sensitive points in knee * Corresponding author. Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, China.

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**Corresponding

author. Acupuncture and Tuina School, Chengdu University of Traditional

Chinese Medicine, Chengdu, Sichuan 610075, China. E-mail: [email protected](Y. Li), [email protected]( F.r. Liang). 1 These

authors contributed equally to this work.

osteoarthritis (KOA), in order to provide a basis for future investigations. Methods: The knee was divided into 12 regions and points palpated in these regions for 36 patients with KOA. A pressure algometer was used to measure the pressure-pain threshold (PPT) of the points, including a-shi points and 13 known acupoints on the knees. Five points with the lowest pain threshold on

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each knee were regarded as the pain-sensitive points. Results: The pain-sensitive points were mainly located in the vastus medialis,

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semimembranosus, semitendinosus, sartorius, gracilis, and gastrocnemius of knee. Weizhong (BL40), Ququan (LR8), Yingu (KI10), Xiguan (LR7), and Yinlinquan (SP9) were the top 5 most frequent pain-sensitive acupoints. The

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pain-sensitive a-shi points in each region showed similar degrees of sensitivity. No significant differences of PPTs were found among 13 pain-sensitive

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acupoints.

Conclusions: The pain-sensitive points of KOA were mainly distributed within

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the medial regions of knee. Since this was a pilot study with a small sample size,

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further large studies are needed to confirm these findings.

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Abbreviations: KOA, knee osteoarthritis; PPT, the pressure-pain threshold;

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TCM, traditional Chinese medicine

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Keywords: Knee osteoarthritis; Pain-sensitive points; Acupuncture; Pilot study

1. Introduction Knee osteoarthritis (KOA), one of the most common degenerative joint diseases, is pervasive and characterized by chronic joint pain, early morning stiffness and bony crepitus [1, 2]. Nowadays approximately 30% of the global

population over 60 years old are suffering from KOA [3], which has been a leading cause of disability and functional limitation among elderly [4]. Despite the high prevalence of KOA, the conventional treatments, such as NSAIDs, glucosamine and intra-articular injections, are far from satisfactory [5. 6]. When surgical intervention is needed, arthroscopic knee surgery is frequently used before resorting to knee replacement [7]. Given the side-effects of

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conventional medications and the increasing burden of knee surgery [8, 9],

patients increasingly turn to complementary and alternative treatments [10, 11].

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Acupuncture and moxibustion, as a non-pharmacological treatment, has long been an alternative in China and has received increasing attention in many Western countries [12, 13].

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According to the theory of traditional Chinese medicine (TCM), there are

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relationships between disease conditions and their respective acupoints or

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ashi-points. When the body suffers from one disease, these points will become

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sensitized, which is called point sensitization. The effectiveness of acupuncture and moxibustion on KOA has been demonstrated in previous

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systematic reviews and high quality clinical studies, in which the sensitive points were usually chose for treatment [14-17]. Additional, choosing sensitive

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points could achieve superior effects than choosing non-sensitive ones [18]. Therefore sensitive points may be the key factor of effectiveness, which may

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be the reason for the difference of curative effect [19, 20]. Some clinical studies have reported the distribution of sensitive points in

the visceral or musculoskeletal disease, such as functional intestinal disorder,

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shoulder pain and KOA [21-23]. However, there are various types of point sensitization, including pain, force, or heat [19, 24, 25]. Previous studies focused mainly on heat-sensitive points in patients with KOA [23, 26]. Therefore, a research on the distribution of pain-sensitive points is expected to undertaken. This pilot study aimed to observe the distribution of pain-sensitive points in

patients with KOA to supply a basis for future investigation to inform a future randomized controlled trial.

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2. Materials and Methods

2.1 Study design

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An observational pilot experiment (registered on ClinicalTrials. No :

03008668) was conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine (TCM) from October to December in 2016

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(Sichuan, China). The study was approved by the Bioethics Subcommittee of

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West China Hospital, Sichuan University (Approval No. 306).

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2.2 Participants

Participants aged 40 years or older and diagnosed with KOA were eligible

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to participate in the study. The diagnostic criteria of KOA was in accordance with the Chinese Guideline for the Medical Management of Osteoarthritis [27].

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Exclusion criteria were as follows: (1) a diagnosis of skeletal disorders, such as knee joint tuberculosis, tumours, rheumatism, rheumatoid arthritis, lower limb

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joint contusion or other trauma; (2) unable to walk properly due to foot deformity or pain; (3) unable to normally communicate coherently due to mental disorders; (4) those with severe cardiovascular, hepatic, renal disease or other illness; (5)

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women who were pregnant or lactating; (6) participants who had received knee arthroplasty; (7) participants who had received physiotherapy treatments for KOA in the past month; (8) participants who had participated in any other trial in the previous six months

2.3 The Test Regions Based on anatomical structure of knee joint and expert consensus [28], the anterior and posterior surface of the affected knees were divided into 12 regions in 36 patients with KOA (Figure1). Marking methods were as follows: (1) a line drawn horizontally three body inches (cun) above the patella as the

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upper boundary; (2) a line drawn horizontally across ST36 as the lower boundary; (3) two lines drawn horizontally between the upper and lower patella

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respectively; (4) in the front region, two lines drawn vertically across the top corners of the basis patellae respectively; (5) in the back region, two lines drawn vertically trisecting the popliteal area.

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2.4 Selection of the Test Points

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The test points included both acupoints and a-shi points in the testing

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regions. Based on literature [29] and expert consensus, we identified 13

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acupoints for PPT testing of KOA , namely Heding (EX-LE2), Nexiyan(EX-LE4), Dubi (ST35), Xuehai (SP10), Liangqiu (ST34), Yinlingquan (SP9),

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Yanglingquan (GB34), Zusanli (ST36), Weizhong (BL40), Yingu(KI10), Xiguan (LR7), Ququan (LR8), Weiyang (BL39). Similar to traditional acupoints, a-shi

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points, located outside meridians, are also regarded as the respective points of disease conditions on the surface of body [30]. A-shi points were identified

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when the patients felt the sensation of pain, distention, or soreness while the trained acupuncturist pressing vertically downward at an even speed with

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thumb.

2.5 Measurements of PPT The electronic Von Frey (2390-type made by the IITC Company, United States), with a flat contact surface of 0.8 mm diameter rigid tip, was used by a trained acupuncturist to measure the PPT of acupoints and a-shi points. At first,

the verbal instructions were given to the patients: “This is a test of your ability to detect a sensation of a pinprick. The instrument that increase in sharpness will be pressed gently press your test points. You may be feel them firstly, but not feel they are pricking in any way. Eventually a component of pricking will be added to this sensation. Please say “yes” immediately when you feel the slightest pricking sensation [31].” while the patients were instructed to lie down

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with local skin of the knee exposed. The acupuncturist held the detector,

moving the probe tip vertically downward the skin at an even speed. The probe

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tip was immediately removed once the patients felt a sensation of a pinprick,

and the PPT on the detector was digitally recorded [32]. All points were tested three times at an interval of five minutes. The average of the three values was

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taken as the final PPT. The five points with the lowest PPT were selected and

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2.6 Statistical Analysis.

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marked as pain-sensitive points.

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Statistical analysis was performed by SPSS for Windows statistics software (version 21.0). Demographic and PPTs were summarized using frequencies, percentages, mean (±standard deviations), median (interquartile range) as

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appropriate. Comparisons of PPTs among pain-sensitive a-shi points in each region were undertaken using either Kruskal - Wallis Test or Analysis of

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Variance. The same analysis were performed for the comparisons of PPTs among 13 pain-sensitive acupoints. All statistical tests were two-tailed, and P <

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0.05 was taken to indicate statistical significance.

3. Results 3.1 Characteristics of Patients Of the 53 potential patients recruited, 6 did not meet the diagnostic criteria,

7 were excluded due to rheumatoid arthritis and 4 were excluded for having received acupuncture within the last month. A total of 36 patients with KOA (19 cases with KOA in bilateral sides, 9 cases in the left knee, and 8 cases in the right knee, a total of 55 knees) were evaluated in the end. Among them, females accounted for 91.7%. The age of patients ranged from 40 to 78 years old, with a mean age of 57.47±8.22y. The mean weight and height of patients

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was 58.36±8.41kg and 157.28±6.29cm respectively. The mean history of

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KOA was 5.34±5.19 years.

3.2 The Distribution of Pain-Sensitive Points Measured by Von Frey

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A total of 1088 points including 715 acupoints and 373 a-shi points

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in 55 knees were measured by an electronic Von Frey detector. In the

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indicated 12 regions, a total of 275 pain-sensitive points were found. Among them, 153 of them were acupoints and 122 were a-shi points.

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The greatest concentration of 122 a-shi points were located in the I, IV, and VII

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regions, which had 24, 25, and 18 points respectively (Table 1). The pain-sensitive acupoints found 153 times were mainly distributed on Liver Meridian, followed by Spleen Meridian, and on the Bladder Meridian (Figure 2);

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The acupoints BL40, LR8, KI10, LR7, and SP9 were the 5 acupoints were the

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top 5 most frequent pain-sensitive acupoints (Table 2).

3.3 The Comparison of PPTs among Pain- Sensitive Points Detected by Von

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Frey detector

3.3.1 The Comparison of PPTs among Pain- Sensitive A-shi Points in Each Region The results revealed no significant differences in PPTs value among

pain-sensitive a-shi points in each region (P > 0.05) (Figure 3).

3.3.2 The Comparison of PPTs among 13 Pain- Sensitive acupoints No significant differences of PPTs level were found among 13

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pain-sensitive acupoints (P > 0.05) (Figure 4).

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4. Discussion

Sensitive points may not only reflect the pathological phenomenon of

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disease on the body but also represent an optimal target for acupuncture

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treatment [19, 33]. Several studies have reported the distribution of sensitive

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points in different diseases [21-23]. However, little research has been

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conducted to observe the distribution of pain-sensitive points in patients with KOA.

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In our study, a total of 275 pain-sensitive points were found in 55 affected knees. The pain-sensitive a-shi points were mainly located in the I, IV, and VII

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regions, including the vastus medialis, anserine, and lateral gastrocnemius of knee, which were similar to the results of previous study [34-36]. When

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movement such as bending the knee, these muscles will be recruited into contraction or stretching and cause pain. Therefore, the location of pain-sensitive a-shi points may not only relate to the disease conditions but

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also to biological structure of knee. Additionally, all of the acupoints showed different degrees of sensitivity. Such characteristics may relate to acupoint sensitization [35]. According to the theory of TCM and clinical evidence, acupoints may reflect both the physiological functions and pathological states of the body. With a pathological condition, such as KOA, some relevant meridians and acupoints will become sensitized [26]. In addition, the

hyperalgesia and traditional acupoints have certain correlations in anatomic locations and clinical indications [37]. Similar to previous study [21, 24], JIANLIAO (SJ14), JIANYU (LI15) and JIANZHEN (SI9) are sensitized in the shoulder pain. Patients with Gastric Ulcer or Gastritis are more sensitive to ST36, SHANGJUXU (ST37), and XIAJUXU (ST39). An interesting phenomenon was found that the pain-sensitive a-shi points in each region

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showed similar degrees of sensitivity, and no significant differences of PPTs

were found among 13 pain-sensitive acupoints. These may be limited by the

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small sample size. Additionally, the measurement of PPT could be more or

less affected by some external factors, for example the test environment or the concentration of patients during the testing time. Further studies are required to

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minimize these interference factors.

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Several studies have reported that the mechanism of pain sensitization

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may relate to nervous system [38]. When sensitization appears, the central and peripheral sensitization will occur, which are significant mechanisms in

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musculoskeletal pain [36]. Indeed, there have some evidence that peripheral and central sensitization contributes to KOA pain [32, 40]. Emerging evidence

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suggests that hyperalgesia local to the knee may demonstrate peripheral nervous system changes due to prolonged inflammatory processes. while,

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hyperalgesia remote to the knee indicate the involvement of the central nervous system [41]. These central changes are regarded to be initiated by

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ongoing pathological neuronal signals from the joint [42, 43]. To our knowledge, this is the first study to observe the distribution of

pain-sensitive points in patients with KOA. In our study, both a-shi points and acupoints were taken into account. Compared with other studies about measurement of PPT [44, 45], the electronic Von Frey, which provides reliable, quantitative assessment, are more objective, accurate and less time consumption to measure the degrees of pain sensitivity [46]. This pilot study,

offered feasible methods of mapping test regions and PPT measurement to provide beneficial references and help for future study. Currently a large study is being conducted to confirm the regularity of pain-sensitive points distribution. Additionally, by identifying the pain sensitive points associated with KOA, a promising therapeutic effect of acupuncture against KOA is expected to be

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achieved.

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We acknowledge that our study has several limitations. Firstly, only 36

patients with 55 affected knees were evaluated. However, it was a pilot study that we discussed with statisticians, clinical experts, and felt that 36 cases

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were sufficient for pretesting. Secondly, the gender bias existed because of the small sample of the study, higher incidence in women of KOA [47] and the

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enthusiasm of women to participate in the trial, which could lead to internal

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validity limitation. We will continue to recruit subjects to minimize trial deviation

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caused by gender in future studies. Thirdly, the test regions were limited to the local knee joint, ignoring the distal areas. Fourthly, previous research has

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measured the acupoint's area on the body surface [48]. However there still has no definite conclusion about the scope of the acupoints. So we marked the 13

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acupoints according to “WHO standard acupuncture location” before palpation, If points located outside the marked acupoint areas with palpation related pain,

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they were identified as a-shi points. These a-shi points may be within the acupoint area, or may not be, which requires further study in the later stage. Fifthly, pain sensitivity may be associated with KOA symptom severity [41].

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However we did not observe the correlation between the pain-sensitive points and symptom severity. In addition, this observational study, which was lacked a control group, whether the sensitization experienced at points changes as the disease progresses is not known. Further studies are needed to confirm the phenomena observed here.

5. Conclusion

In conclusion, the pain-sensitive acupoints of knee osteoarthritis were mainly distributed in the interior regions of knee. The results of this pilot study may provide feasibility for further study in the area of the distribution of

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pain-sensitive points.

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Funding

This study was supported by the National Natural Science Foundation of

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China (no. 81590955 and no. 81590951).

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Conflict of interests

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The authors declare that they have no conflict of interest.

Acknowledgements

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We thank all authors in this article. The first two authors (YNL and ZYM) contributed equally to this study, they analyzed the data and wrote the paper.

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LY and LFR designed the study and was responsible for obtaining approval by the Chengdu University of Traditional Chinese Medicine. ZX, ZL and ZQH provided language help. ZH,TL and JPL modified the manuscript. WQ and HC

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provided of study materials or patients. All authors read and approved the final version of the manuscript accepted for publication.

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Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization, Arthritis Rheum. 65 (2013):363-372. [46] Baad-Hansen, M. Pigg, P. Svensson, Assessment of Mechanical Pain Thresholds in the Orofacial Region: A Comparison Between Pinprick Stimulators and Electronic Von Frey Device, J Oral Facial Pain Headache. 30 (2016) 338-345.

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[47] Q. Pan, M.I. O'Connor, R.D. Coutts, S.L. Hyzy, R. Olivares-Navarrete, Z. Schwartz, B.D. Boyan, Characterization of osteoarthritic human knees indicates potential sex differences, Biol Sex Differ. 7(2016) 27.

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[48] Y.L. Zhang, X.S. Lai, Measurement of Acupoint's Area on Body Surface:Present Situation and Thinking, JCAM. 27 (2011) 50-52.

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FIGURE 1: Mapping Test Regions

A. The test regions mapped in the anterior of knee; B. The test regions

A

mapped in the posterior of knee. I. The vastus medialis muscle of the starting and ending point; II. Bursae suprapatellaris and the start-end point of rectus femoris; III.Vastus lateralis of the starting and ending point; IV. The medial retinaculum, sartorius, gracilis and semimembranosus cross fusion region; V. Patellar; VI. Patellar retinaculum and lateral collateral ligament fusion region; VII. Tibial plateau, tibial lateral ligament, sartorius, gracilis, parts of

semitendinosus muscle composed of anserine bursa, lateral gastrocnemius; VIII. Patellar ligament and bursa region; IX. The tibial plateau and tibialis anterior; X. Parts of biceps femoris and semitendinosus; XI. popliteal fossa; XII.

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Gastrocnemius.

A

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FIGURE 2: The distribution of meridians in the pain-sensitive acupoints.

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FIGURE 3: There was no significant difference in PPTs among

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M

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pain-sensitive a-shi points in each regions (P > 0.05).

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FIGURE 4: No significant differences of PPTs were found among 13

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N

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pain-sensitive acupoints (P > 0.05).

TABLE 1. The Distribution and PPTs of Pain-Sensitive Ashi Points in Each Region Detected by Von Frey Detector.

Ashi Points, n

PPT, Q2 (IQR) (g)

I

24

42.19 (42.74)

IIa

0

/

III

10

32.53 (42.87)

IV

25

42.13(27.45)

Vb

0

VI

7

VII

18

VIIIc

2

IX

11

Xd

1

XI

10

XII

14

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32.20 (26.44)

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A

N

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35.75 (23.72) /

23.13 (27.57) / 45.86 (43.58) 30.74 (11.63)

number of points is less than 4, which cannot be represented by the median.

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a,b,c,d,The

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PPT: the pressure-pain threshold; Q2: median; IQR:interquartile range.

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Regions

TABLE 2. The Distribution and PPTs of Pain-Sensitive Acupoints Detected by Von Frey

N(Times)

PPT, Q2(IQR) (g)

ST 34

8

41.35(41.22)

ST 35

8

38.03(30.98)

ST 36

4

56.57(66.02)

SP 9

11

40.52(43.50)

SP 10

16

54.81(62.39)

BL 39

4

93.29(57.77)

BL 40

22

43.86(37.14)

KI 10

19

40.30(41.60)

GB 34

5

LR 7

18

LR 8

19

EX-LE2

9

EX-LE4

10

U

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Meridian Acupoints

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A

N

59.43(28.56) 42.41(31.78) 34.43(43.30) 39.40(70.62) 33.91(47.27)

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PPT: the pressure-pain threshold; Q2: median; IQR:interquartile range.

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Detector