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The objective of this review is to investigate the detailed existing scientific information about the clinical efficacy of acupuncture on rheumatoid arthritis (RA) conditions and to reveal the proposed mechanisms.
We searched the PubMed, EMBASE, Cochrane, AMED (Allied and Complementary Medicine), NCCAM (The National Center for Complementary and Alternative Medicine), and CNKI (China National Knowledge Infrastructure) databases to identify relevant monographs and related references from 1974 to 2018. Chinese journals and theses/dissertations were hand searched.
Arthritis Curehow to Arthritis Cure for 43 studies were recruited. Each research was analyzed for study design, subject characteristics, intervention, selected acupoints, assessment parameters, proposed mechanisms, and results/conclusions.
In our review, we concluded that acupuncture alone or combined with other treatment modalities is beneficial to the clinical conditions of RA without adverse effects reported and can improve function and quality of life and is worth trying. Several important possible mechanisms were summarized including anti-inflammatory effect, antioxidative effect, and regulation of immune system function. However, there is still inconsistency regarding the clinical efficacy and lack of well-designed human/animal double-blinded RCTs. Future discussion for further agreement on taking traditional Chinese medicine (TCM) theory into consideration as much as possible is a top priority.
Rheumatoid arthritis (RA) is the most common inflammatory arthritis and has been known as a chronic and autoimmune disease involving inflammatory condition characterized with symmetrical and persistent synovitis and destructive polyarthritis . RA is also associated with morbidity, chronic disability, and poor quality of life and the cost of care is huge [2, 3]. The estimated prevalence of RA is 0.2–1% . As many factors like susceptibility genes, disease-causing immune cells, cytokine, and signal transduction networks are involved in the pathogenesis of RA , the treatment of RA has always been a challenge. The mainstream of the management regarding RA is the use of nonsteroid anti-inflammatory drugs, disease-modifying antirheumatic drugs, analgesics, and biological agents . But the concerns may arise when taking accompanying side effects and toxicity into consideration . Given the fact of the expanding awareness of unwanted side effects of pharmaceutical treatment, there has been an increased utilization of acupuncture as a contemporary healthcare option which has been reported as a kind of safe management [7, 8].
According to traditional Chinese medicine (TCM) theory, RA is categorized under the “Bi” or impediment disease, which means a group of diseases caused for 1 last update 2020/08/05 by the invasion of wind, cold, dampness, or heat pathogen on the meridians involving muscles, sinews, bones, and joints, manifested by local pain, soreness, heaviness, or hotness, and even articular swelling, stiffness, and deformities, also referring to arthralgia.According to traditional Chinese medicine (TCM) theory, RA is categorized under the “Bi” or impediment disease, which means a group of diseases caused by the invasion of wind, cold, dampness, or heat pathogen on the meridians involving muscles, sinews, bones, and joints, manifested by local pain, soreness, heaviness, or hotness, and even articular swelling, stiffness, and deformities, also referring to arthralgia.
Acupuncture has been regarded as an important part of TCM and has been used for thousands of years to treat various clinical disorders including “Bi” or RA like conditions based on TCM theory. There has been a trend to use complementary and alternative medicine (CAM) as 30–60% of rheumatic patients used CAM . In the United States, a small but significant linear increase in the use of acupuncture (from 1.4% in 2007 to 1.5% in 2012 of the US adults) was reported . About 41% of patients with rheumatic diseases sought the help from acupuncture in Israel . In Taiwan, a recent population-based study revealed the high prevalence and specific usage patterns of TCM including acupuncture in the RA patients . 54.6% of the newly RA user of CAM selected acupuncture only in Korea .
However, discrepancy exists between previously conducted investigations and reviews regarding clinical efficacy of acupuncture for RA [14, 15]. As early as in 1985, a literature analysis of the efficacy using acupuncture for RA was done by Bhatt-Sanders and no conclusion was drawn . Ernst and Posadzki suggested that the evidence to support the effectiveness of CAM as a treatment option for RA has also been ambiguous . On the other hand, Hughes concluded that acupuncture elicited a range of effects which contributed to improvements in RA patients''s opinions or pure descriptive literature reviews/systemic reviews.
149 studies from 1974 to 2018 were analyzed and 43 studies were recruited into the review. As there are not many researches specific for acupuncture and RA, we tried to include as many articles as possible. The study designs, subjects'' left ankle diameter, serum TNF-α, IL-1α, and ICAM-1
Most of the studies (33 out of 43) are randomized controlled trails (RCT) [22, 23, 25–27, 29, 30, 32–35, 37–45, 48–50, 52, 54–57, 59–62, 66]; 4 of them are double-blinded RCT [49, 54, 61, 62]. There are two single case studies [31, 36]. The rest of the analyzed articles are clinical trials without mentioned randomization or controls groups [24, 28, 46, 47, 51, 53, 58, 63–65].
There are studies with human RA patients [23, 24, 28–30, 33–37, 42–66] and studies with animal subjects; most of them are rats [22, 26, 31, 32, 38–41] and rabbits [25, 27] with an established RA model group by in vivo injection of adjuvant components.
Liu et al. included 180 human RA subjects with peptic ulcer to investigate the efficacy of ginger-partitioned acupoint stimulation which is known to be the research with most subjects included . 5 studies contained human subjects more than 100 [23, 29, 37, 42, 60]. 2 researches focused on elderly RA patients [24, 50], one focused on 6 female RA patients , and 3 researches recruited healthy human subjects for control as well [33, 34, 66].
There are 18 researches written in English [22, 24, 31, 34, 36–38, 43, 46, 47, 49, 51–54, 61, 62, 64] and the rest of the analyzed researches in Chinese. English abstracts can be found for most of the studies in Chinese.
The selection of acupoints has not been very unanimous according to the authors''s adjuvant , or ovalbumin and extra freezing process to imitate the cold syndrome as classified in TCM , the disease progression may not be the same in real RA patients, and most of the investigations did not have adequate follow-up period till the chronic stage was achieved (e.g., 10 days ). As compared to most human studies, there were at least 3–12 weeks of treatment and follow-up with the longest follow-up period of 3 years . This made the conclusions drawn less practical and applicable for RA patients. But Jie et al. used buccal acupuncture and found that central analgesic effect with upregulation of endorphin and CCK-8 in cerebrospinal fluid could be observed with needle retaining for 30 minutes in RA rabbits; this is the shortest observation but with good results .
Some authors provided better clinical efficacy using different needling techniques including warm needling [26–28, 33, 41, 55, 63, 65], plus herb steaming , needle-sticking method , reinforcing-reducing/twirling-reinforcing needling , and moxibustion [57, 66]. EA was used in several studies [22, 30–32, 36, 43, 44, 52, 54, 60], and some authors suggested a better effect than traditional acupuncture [43, 44, 52, 54]. Several studies employed sham acupuncture or EA as the control group [22, 38, 49, 54, 61, 62]. Special forms of acupoints stimulation included laser [24, 34], ginger-partitioned therapy , and millimeter waves .
We found an interesting fact that acupoint ST36 was used in almost every research and followed by GB34 and LI4. According to TCM theory, RA should fit the disease condition called “Bi” or impediment disease, which means any disease pattern that results from blockage of the meridians occurring when wind, cold, and dampness invade the fleshy exterior and the joints, and that manifests in symptoms such as joint pain, sinew and bone pain, and heaviness or numbness of the limbs as stated in Elementary Questions (Su Wen, bi lun). Distinction is made between three pattern types, each of which corresponds to a prevalence of one of those three evils: wind impediment (or moving impediment) characterized by wandering pain and attributed to a prevalence of wind; cold impediment (or painful impediment) characterized by acute pain and attributed to a prevalence of cold; damp impediment (or fixed impediment) characterized by heaviness and attributed to a prevalence of dampness. A fourth type, heat impediment, arises when the three evils transform into heat. The basic philosophy of how all the acupoints were selected derived from the above theory. As a result, the number of acupoints used seems not to affect the clinical efficacy.
Measurements of quality of the 1 last update 2020/08/05 life domain have gained more interest among RA patients than other disease-related parameters such as inflammatory biomarkers or joint counts . In this review, some studies have adopted related questionnaires [24, 30, 36, 37, 46, 62] and acupuncture was able to improve the quality of life except in one study .Measurements of quality of life domain have gained more interest among RA patients than other disease-related parameters such as inflammatory biomarkers or joint counts . In this review, some studies have adopted related questionnaires [24, 30, 36, 37, 46, 62] and acupuncture was able to improve the quality of life except in one study .
Anti-inflammatory effect has been the most well-known mechanism of how acupuncture works for RA as many studies in this review used inflammatory biomarkers for comparison such as ESR, CRP, RF, IL, NF-κB, and TNF-α. Most of the studies comparing these biomarkers indicated the anti-inflammatory effect of acupuncture [22–24, 26, 31, 32, 37–39, 41, 43, 44, 50–55, 58, 59, 66]. Wang et al. indicated the reduction of ESR and CRP after acupuncture in RA subjects in their review as well . Han et al. thought that acupuncture can lower TNF-α and VEGF in peripheral blood and joint synovia to improve the internal environment which is beneficial for RA .
Dong et al. indicated that toll-like receptor (TLR) signaling pathway contributed to the development and progression of RA and acupuncture could reduce the expression of TLR4, thus leading to anti-inflammation . However, some authors did find clinical effect but not via anti-inflammation [46, 49]. Efthimiou and Kukar indicated that even though no clear anti-inflammatory effect has been demonstrated, acupuncture may still be a useful adjuvant for pain . In our review, we think anti-inflammatory effect acts in certain occasion to improve the RA conditions.
Another possible mechanisms could be attributed to the antioxidative effect (such as inducing the increased activities of SOD and catalase in the serum of RA, alleviating oxidative stress and inflammation, and improving antioxidant and energy metabolic status) [33, 34, 47] and triggered release of endorphins  and regulation of immune function as IgG, IgA, and IgM decreased, while IgE did not change evidently after acupuncture in 12 RA patients [23, 32, 64–66].
Forestier et al. concluded in 2009 the evidence level of acupuncture for RA is limited to professional agreement with no scientific evidence . Along with other inconclusive information regarding the clinical efficacy [54, 72], well-designed RCTs are warranted . Most animal studies lack the consistency in establishing the RA model such as the standard injected substance, the dosage, the injected site, the duration of observation after injection, the treatment protocol including acupoints selection, animal acupuncture localization standard, TCM syndrome differentiation, the period of follow-up, and assessment parameters. As for human study, the most important thing is to decide if treatment protocol should vary according to TCM differentiation. Although different mechanism leads to different study design in terms of the parameters that will be assessed, efforts should be put on the standardization and it should be thought whether other methods like functional imaging test would be appropriate.
Arthritis Curehow to Arthritis Cure for Acupuncture has its root in TCM and traditionally TCM has one distinguished character; that is, it does not completely seek the specific pathogen and pathological changes in a specific organ or individual, but it seeks the disturbances among the self-controlled systems by analyzing all symptoms and signs. The TCM intervention is based on the differentiation of symptoms to clarify what is wrong in the self-controlled system. TCM seeks the therapeutic mechanism from the integrity and balance, in each individual and between the individual and the environment. The therapeutics work by activating and improving system connection and enhancing human resistance. The mechanism in TCM is not like modern medicine that seeks the mechanism from cellular or molecular perspectives . In light of this, to attend simultaneously to a well-designed RCT with every possible variable controlled and TCM theory is extremely difficult. Future agreement on this issue warrants extensive discussion.
Arthritis Curehow to Arthritis Cure for Although we have tried our best searching and analyzing all the eligible articles, some earlier works are not available due to language barriers. We were not able to level the quality of each article as there are not many of them. We also exclude some investigations such as ones using venom acupuncture or gold thread embedding as more information about efficacy and mechanism may not be revealed. Some Chinese articles did bring about the treatment philosophy according to TCM, but it was very hard to organize and summarize well.
In our review, we concluded that acupuncture alone or combined with other treatment modalities is beneficial to the clinical conditions of RA without adverse effects reported and can improve function and quality of life and is worth trying. Several important possible mechanisms were summarized including anti-inflammatory effect, antioxidative effect, and regulation of immune system function. However, there is still inconsistency regarding the clinical efficacy and lack of well-designed human/animal double-blinded RCTs. Future discussion for further agreement on taking TCM theory into consideration as much as possible is a top priority.
This work is supported by research grants from China Medical University, Taiwan (CMU103-S-48).
The authors declare that there are no conflicts of interest regarding the publication of this paper.