This article is a commentary on:
Efficacy and Safety of Acupuncture on Symptomatic Improvement in Primary Sjögren’s Syndrome: A Randomized Controlled Trial
Hsin-Yuan Chen1,2
Ching-Mao Chang- 1Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- 2School of Post-baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan
- 3Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- 4Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
A Commentary on
Efficacy and safety of acupuncture on symptomatic improvement in primary Sjögren's syndrome: A randomized controlled trial
by Zhou, X., Xu, H., Chen, J., Wu, H., Zhang, Y., Tian, F, et al. (2022). Front Med. 9:878218. doi: 10.3389/fmed.2022.878218
In the prospective study titled “Efficacy and safety of acupuncture on symptomatic improvement in primary Sjögren's syndrome: a randomized controlled trial” (1), Prof. Jiang and colleagues evaluated acupuncture treatment of the main symptoms of primary Sjögren's syndrome (pSS), specifically dryness, pain, and fatigue. Their results suggested that acupuncture did not improve these symptoms more than a placebo did. However, in contrast to pharmacological interventions (2–6), acupuncture therapies depend on procedural expertise and are often complex and multifaceted.
Moreover, prior clinical and basic scientific literature support the possibility of specific effects being generated by sham acupuncture (7). It is therefore possible that acupuncture's reported failure to improve the main symptoms of pSS was related to the authors' use of the same acupoints and manipulations in their real and sham acupuncture groups; and that the reported lack of inter-group differences could have been influenced, at least in part, by the ostensibly sham condition having real effects, or at any rate, strong placebo effects. To avoid such a possibility, recent acupuncture trials have used non-acupoint locations for sham acupuncture. Zhao et al. (8), for example, adopted such an approach and found that true acupuncture was more closely associated with long-term reductions in migraine recurrence that either sham acupuncture or being placed on a waiting list.
According to Zhang et al.'s study published in 2022 in the BMJ (9), trialists should carefully consider the desirability of sham conditions that might lead to underestimation of acupuncture treatments' clinical effects. The lack of a placebo effect in prior acupuncture trials raised concerns about the integrity of the sham blinding, unintentional crossover in the sham treatment groups, and/or a physiological effect of the sham acupuncture (8). Hershman et al., to address prior concerns about these possible sham effects by ascertaining whether psychological effects are in play, designed a study with a waitlist control group whose members received no therapeutic intervention (10). In such a control group, the placebo effects arising from the acupuncturist-patient relationship and patients' expectations about the benefits of acupuncture may be zero, unlike those experienced by a sham acupuncture group (8).
Traditional Chinese medicine holds that an acupoint is a specific point on the body's surface that is inactive when the body is in a healthy condition, but which can be activated by certain stimuli. Brain activation associated with acupuncture stimulation has been found to be influenced by enhanced bodily awareness and bodily attention around the acupoints (11); and it has been shown that the spatial configurations of De-qi sensations in response to tactile stimulation can be influenced by visual bio-signal information. This suggests that information on physiological responses to acupuncture stimulations can change participants' expectations of how somatic sensations are perceived, as well as their expectations of how they will interpret the stimulations themselves. Moreover, expectations can be formed via various mechanisms, including verbal suggestions and conditioning (12). Therefore, when Prof. Jiang and colleagues informed their subjects that they would undergo “a new method of acupuncture”, it could have affected the latter's expectations.
The meaning of de-qi was acupuncture-related sensations of four types, i.e., soreness, numbness, fullness/distention and heaviness. However, factors related to understanding de-qi, such as its mechanisms, its related organs, its biological parameters, and even its relationship with acupuncture's efficacy remain unclear. According to Liang et al.'s study published in 2013 (13), volunteers could not distinguish between the de-qi feelings induced by real and sham needles, irrespective of whether the shift was from real to sham or vice versa; and a non-invasive placebo acupuncture device could simulate the de-qi sensation as effectively as real acupuncture. In another review (14), we found that real and sham acupuncture modulated different brain regions/networks, which may suggest that different mechanisms underlie these two techniques (15, 16). Hence, the choice of sham acupoints could be an important factor in sham acupuncture's efficacy.
In conclusion, due to the use of the same acupoints across both the real and sham acupuncture groups, a variety of stimuli could have had similar responses; acupuncture stimulations also can affect participants' expectations; and the lack of a waiting-list group is concerning. Hence, we are not convinced by Prof. Jiang and colleagues' results that acupuncture treatment had no value in improving pSS symptoms.
Author contributions
H-YC, J-HW, H-CL, Y-TS, C-MY, and C-MC were responsible for the study concept and design, modification of the study design, and review and interpretation of the data. H-YC, J-HW, and H-CL were responsible for drafting the manuscript. C-MY and C-MC made modifications to the study design and revised the manuscript. H-YC, J-HW, H-CL, and Y-TS contributed to the collection and analysis of data. H-CL, Y-TS, C-MY, and C-MC contributed to the interpretation of the data and revised the manuscript. All authors read and approved the final manuscript.
Funding
This study was supported by the Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei, Taiwan and National Science and Technology Council, Taipei, Taiwan (NSTC-111-2320-B-075-006-MY2).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
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References
1. Zhou X, Xu H, Chen J, Wu H, Zhang Y, Tian F, et al. Efficacy and safety of acupuncture on symptomatic improvement in primary Sjogren's syndrome: a randomized controlled trial. Front Med. (2022) 9:878218. doi: 10.3389/fmed.2022.878218
2. Yu MC, Lin SK, Lai JN, Wei JC, Cheng CY. The traditional Chinese medicine prescription patterns of Sjogren's patients in Taiwan: a population-based study. J Ethnopharmacol. (2014) 155:435–42. doi: 10.1016/j.jep.2014.05.049
3. Chang CM, Chu HT, Wei YH, Chen FP, Wang S, Wu PC, et al. The core pattern analysis on Chinese herbal medicine for Sjogren's syndrome: a nationwide population-based study. Sci Rep. (2015) 5:9541. doi: 10.1038/srep09541
4. Chen HH, Lai JN, Yu MC, Chen CY, Hsieh YT, Hsu YF, et al. Traditional Chinese medicine in patients with primary Sjogren's syndrome: a randomized, double-blind, placebo-controlled clinical trial. Front Med. (2021) 8:744194. doi: 10.3389/fmed.2021.744194
5. Lee GA, Chang CM, Wu YC, Ma RY, Chen CY, Hsue YT, et al. Chinese herbal medicine SS-1 inhibits T cell activation and abrogates T(H) responses in Sjogren's syndrome. J Formos Med Assoc. (2021) 120:651–659. doi: 10.1016/j.jfma.2020.07.024
6. Chang CM, Wu PC, Lin JR, Jan Wu YJ, Luo SF, Hsue YT, et al. Herbal formula SS-1 increases tear secretion for Sjogren's syndrome. Front Pharmacol. (2021) 12:645437. doi: 10.3389/fphar.2021.645437
7. Zucker NA, Tsodikov A, Mist SD, Cina S, Napadow V, Harris RE. Evoked pressure pain sensitivity is associated with differential analgesic response to verum and sham acupuncture in fibromyalgia. Pain Med. (2017) 18:1582–1592. doi: 10.1093/pm/pnx001
8. Zhao L, Chen J, Li Y, Sun X, Chang X, Zheng H, et al. The long-term effect of acupuncture for migraine prophylaxis: a randomized clinical trial. JAMA Intern Med. (2017) 177:508–15. doi: 10.1001/jamainternmed.2016.9378
9. Zhang YQ, Jiao RM, Witt CM, Lao L, Liu JP, Thabane L, et al. How to design high quality acupuncture trials-a consensus informed by evidence. BMJ. (2022) 376:e067476. doi: 10.1136/bmj-2021-067476
10. Hershman DL, Unger JM, Greenlee H, Capodice JL, Lew DL, Darke AK, et al. Effect of acupuncture vs sham acupuncture or waitlist control on joint pain related to aromatase inhibitors among women with early-stage breast cancer: a randomized clinical trial. JAMA. (2018) 320:167–176. doi: 10.1001/jama.2018.8907
11. Song HS, Jung WM, Lee YS, Yoo SW, Chae Y. Expectations of the physiological responses can change the somatosensory experience for acupuncture stimulation. Front Neurosci. (2019) 13:74. doi: 10.3389/fnins.2019.00074
12. Aichner S, Haile A, Hoffmann V, Olliges E, Tschop MH, Meissner K. The role of tactile stimulation for expectation, perceived treatment assignment and the placebo effect in an experimental nausea paradigm. Front Neurosci. (2019) 13:1212. doi: 10.3389/fnins.2019.01212
13. Liang ZH, Xie CC, Li ZP, Zhu XP, Lu AP, Fu WB. Deqi sensation in placebo acupuncture: a crossover study on chinese medicine students. Evid Based Comp Alternat Med. (2013) 2013:620671. doi: 10.1155/2013/620671
14. Chang CM, Yang CP, Yang CC, Shih PH, Wang SJ. Evidence of potential mechanisms of acupuncture from functional MRI data for migraine prophylaxis. Curr Pain Headache Rep. (2021) 25:49. doi: 10.1007/s11916-021-00961-4
15. Harris RE, Zubieta JK, Scott DJ, Napadow V, Gracely RH, Clauw DJ. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage. (2009) 47:1077–85. doi: 10.1016/j.neuroimage.2009.05.083
Keywords: acupuncture, Sjögren's syndrome, traditional Chinese medicine, sham effects, auto-immune
Citation: Chen H-Y, Wu J-H, Lin H-C, Su Y-T, Yen C-M and Chang C-M (2023) Commentary: Efficacy and safety of acupuncture on symptomatic improvement in primary Sjögren's syndrome: A randomized controlled trial. Front. Med. 9:1098862. doi: 10.3389/fmed.2022.1098862
Received: 15 November 2022; Accepted: 14 December 2022;
Published: 04 January 2023.
Edited by:
Jing He, Peking University People's Hospital, ChinaReviewed by:
James Cheng-Chung Wei, Chung Shan Medical University Hospital, TaiwanLiwei Yin, Guangzhou University of Chinese Medicine, China
Copyright © 2023 Chen, Wu, Lin, Su, Yen and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ching-Mao Chang, 
magicbjp@gmail.com