The course of rheumatoid arthritis is variable, following a pattern of relapses and remissions.(Masi 1983) However, within about 2 years of diagnosis, patients usually have moderate disability and, after 10 years, around 30% are severely disabled.(NICE 2008) People with rheumatoid arthritis have a reduced life expectancy compared with healthy controls, and have excess cardiovascular disease mortality.(Goodson 2005)
The cause of rheumatoid arthritis is, as yet, unknown. Infection with a micro-organism in those genetically susceptible, hormonal influences, obesity, diet, and cigarette smoking have all been implicated as risk factors.(Silman 2004)
The aim of treatment is to control pain and inflammation, reduce joint damage, disability and loss of function, achieve low disease activity or remission, and improve quality of life.(NICE 2008; Smolen 2007) A variety of drugs are used, including NSAIDs, analgesics, corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs) like methotrexate, and ‘biologic’ drugs that block tumour necrosis factor-alpha (TNFα) such as etanercept, infliximab or adalimumab.(NICE 2008) None-drug treatments such as physiotherapy may also be used.(NICE 2008)
Goodson N et al. Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s. Ann Rheum Dis 2005; 64: 1595-601.
Masi AT. Articular patterns in the early course of rheumatoid arthritis. Am J Med 1983; 75(suppl6A): 16-26.
National Institute for Health and Clinical Excellence, 2007. Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis [online]. Available: http://www.nice.org.uk/nicemedia/pdf/TA130guidance.pdf
Panayi GS. B cells: a fundamental role in the pathogenesis of rheumatoid arthritis? Rheumatology 2005; 44 (suppl 2): ii3-ii7.
Östör AJ, Conaghan PG. Tight control in rheumatoid arthritis improves outcomes. Practitioner 2009; 253: 29-32.
Rituximab and abatacept for rheumatoid arthritis. DTB 2008; 46: 57-61.
Silman AJ. Rheumatoid arthritis. In: Silman AJ, Hochberg MC, eds. Epidemiology of the rheumatic diseases, 2nd ed. Oxford, Oxford Press, 2004: chapter 2, 31-71.
Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2003; 2: 473-88.
Smolen JS, et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 2007; 66: 143-50.
How acupuncture can help
Systematic reviews have come up with conflicting conclusions regarding the effects of acupuncture treatment for rheumatoid arthritis. One found that the data suggest favourable effects of moxibustion (alone or combined with conventional drugs) on response rate compared with conventional drug therapy.(Choi 2011) The other two reviews found acupuncture to be as good as or better than drugs, but with no consistent advantage over sham acupuncture controls.(Wang 2008; Lee 2008)
More recent trials have been small and do not present a compelling case for upgrading the reviews’ conclusions. It appears likely that some people may benefit from acupuncture treatment,(Lao 2010) but it is not known what proportion this may be, and to what degree and how acupuncture would compare to other possible interventions. More research is needed.
In general, acupuncture is believed to stimulate the nervous system and cause the release of neurochemical messenger molecules. The resulting biochemical changes influence the body’s homeostatic mechanisms, thus promoting physical and emotional well-being. Stimulation of certain acupuncture points has been shown to affect areas of the brain that are known to reduce sensitivity to pain and stress (Hui 2010) It has also be shown to reduce inflammation, by promoting release of vascular and immunomodulatory factors.(Zijlstra 2003; Kavoussi 2007)
Acupuncture treatment may help to relieve pain and improve function in patients with rheumatoid arthritis by:
- decreasing the proinflammatory cytokines IL-1 and IL-6 and increasing the inhibitory cytokines IL-4 and IL-10 (Ouyang 2010);
- inducing vasoactive intestinal peptide expression, an anti-inflammatory neuro-peptide (He 2011);
- inhibiting the function of synovial mast cells (which are substantially involved in the initiation of inflammatory arthritis) (He 2010);
- upregulating plasma adrenocorticotropic hormone, downregulating serum cortisol levels and synovial nuclear factor-kappa B p 65 immunoactivity, and restoring the hypothalamus-pituitary-adrenal axis (HPAA).(Gao 2010);
- stimulating nerves located in muscles and other tissues, which leads to release of endorphins and other neurohumoral factors, and changes the processing of pain in the brain and spinal cord (Pomeranz 1987; Han 2004; Zhao 2008; Cheng 2009);
- increasing local microcirculation (Komori 2009), which aids dispersal of swelling.
|Choi TY et al. Moxibustion for rheumatic conditions: a systematic review and meta-analysis. Clin Rheumatol. 2011 Feb 18. [Epub ahead of print]|
A systematic review that pooled data from 14 randomised controlled trials testing effectiveness of moxibustion for major rheumatic conditions. Trials were included if moxibustion was used alone (8 trials) or as a part of a combination therapy with conventional drugs (6 trials) for rheumatic conditions. All were of low methodological quality. The data suggested favourable effects of moxibustion alone on response rate compared with conventional drug therapy (p<0.02). the results also suggested favourable effects of moxibustion plus drug therapy on response rate compared with conventional alone p 0 02reviewers concluded that trials included in this review were low methodological quality making it difficult to draw firm conclusions
|Wang C et al. Acupuncture for pain relief in patients with rheumatoid arthritis: a systematic review. Arthritis Rheum 2008; 59: 1249-56.||A systematic review that assessed the efficacy of acupuncture on pain relief in patients with rheumatoid arthritis (RA). In all, 8 randomised controlled trials, involving a total of 536 patients, were included. The outcome measures were pain, measured by tender joint count (TJC) or a pain scale, morning stiffness, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. There were 4 placebo-controlled trials and 4 active-controlled trials. Average study duration was 11 weeks. Six studies reported a decrease in pain for acupuncture versus controls. In addition, 4 studies reported a significant reduction in morning stiffness, but the difference was nonsignificant versus controls. With regard to inflammatory markers, 5 studies observed a reduction in ESR and 3 observed a CRP level reduction; only 1 study showed a significant difference for both ESR and CRP. The reviewers concluded that there were some favourable results in active-controlled trials, but conflicting evidence in placebo-controlled trials concerning the efficacy of acupuncture for RA.|
|Lee MS et al. Acupuncture for rheumatoid arthritis: a systematic review. Rheumatology 2008; 47: 1747-53.|
|A systematic review that evaluated the evidence on acupuncture for treating patients with rheumatoid arthritis (RA). It included 8 randomised clinical trials of acupuncture, with or without electrical stimulation or moxibustion. Four trials compared the effects of manual or electro-acupuncture with penetrating or non-penetrating sham acupuncture and failed to show specific effects of acupuncture on pain or other outcome measures. One trial compared manual acupuncture with indomethacin and suggested favourable effects with acupuncture in terms of total response rate. Three trials tested acupuncture plus moxibustion versus conventional drugs and failed to show that it was superior to conventional drugs in terms of response rate, pain reduction or joint swelling. The reviewers concluded that penetrating or non-penetrating sham-controlled trials have failed to show specific effects of acupuncture for pain control in patients with RA.|
|Lao WN et al. Effects of acupuncture on rheumatoid arthritis. International Journal of Rheumatic Diseases. Conference: 14th Congress of Asia Pacific League of Associations for Rheumatology, APLAR 2010 Hong Kong Hong Kong. Conference Publication 2010; 13: 231.||An uncontrolled pilot study that explored the effects of acupuncture on disease activity, pain scores, functional ability and quality of life in 8 patients with RA (6 were positive for rheumatoid factor). No change in disease modifying anti-rheumatic drugs (DMARDs) was allowed 3 months before the study. Tender joint count improved by 33.3% to 100% in six patients. The visual analogue scale for pain score improved by 12.5% to 87.5% in four patients. Disease activity score using 28-joint counts dropped by 3.4% to 29.1% in 6 patients. Health assessment questionnaire score remained unchanged in five patients and improved by 37% to 60% in two patients. Physical well- being improved by 28.6% to 71.4% and social well-being improved by 4.4% to 75% in half of the patients, emotional well-being improved by 25% to 57.2% in three patients, functional well-being improved by 16.7% to 35.3% in two patients, fatigue sub-scale improved by 10% to 56.5% in three patients. No patients required adjustment of DMARDs, anti-inflammatory drugs or steroid during the therapy. The researchers concluded that their observations suggest acupuncture may be helpful in alleviating pain, improving disease activity, quality of life and functional ability in some patients with RA.|
|Bernateck M et al. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: A randomized controlled trial – Auricular acupuncture and autogenic training in rheumatoid arthritis. Forschende Komplementarmedizin 2008; 15: 187-93.|
A randomised controlled trial to compare the efficacy of auricular electroacupuncture (EA) with autogenic training (AT) in 44 patients with RA. At the end of the treatment and at 3-month follow-up a clinically meaningful and statistically significant improvement (p<0.05) could be observed in all outcome parameters both groups contrast to the at group onset of these effects ea already after 2nd treatment week 4th reported significantly less pain than p=”0.020).” end 7th assessed their as more improved erythrocyte sedimentation rate was reduced and serum concentration tumour necrosis factor-alpha increased compared. The researchers concluded that the adjuvant use of both EA and AT in the treatment of RA resulted in significant short- and long-term treatment effects. The treatment effects of auricular EA were more pronounced.
|Zanette S de A et al. A pilot study of acupuncture as adjunctive treatment of rheumatoid arthritis. Clinical Rheumatology 2008; 27: 627-35.|
|A double-blind randomised controlled pilot study that looked at the efficacy of acupuncture as an adjuvant treatment in the management of 40 patients with active rheumatoid arthritis (RA). They were allocated to receive a standard protocol of acupuncture (AC) or superficial acupuncture at non-acupuncture points (control AC) for 9 weeks. The primary outcome was achievement of 20% improvement according to the American College of Rheumatology (ACR) 20 criteria but this showed no significant difference between the groups , either at the end of treatment (p=0.479) or after 1 month of follow-up (p=0.068). Only the AC group showed significant improvement over baseline for a range of secondary clinical measures. Nevertheless, it was only statistically superior to the control for the patient and physician global assessment of treatment and physician global assessment of disease activity, not for other clinical and laboratory measures… The researchers concluded that there was no significant difference in the proportion of patients that reached ACR20 between the AC and control AC groups, but that this negative result could be related to the small sample size, selection of patients, type of acupuncture protocol applied, and difficulties in establishing an innocuous and trustworthy placebo group to studies involving acupuncture.|
|Tam LS et al. Acupuncture in the treatment of rheumatoid arthritis: A double-blind controlled pilot study. BMCComplementary and Alternative Medicine 2007; 7: 35.|
|A randomised double-blind placebo-controlled pilot study of acupuncture to obtain preliminary data on efficacy and tolerability of 3 different forms of acupuncture treatment as an adjunct for the treatment of chronic pain in patients with rheumatoid arthritis (RA). A total of 36 patients were allocated to electroacupuncture (EA), traditional Chinese acupuncture (TCA) or sham acupuncture (Sham). The primary outcome measure was change in the pain score. At week 10, the pain score remained unchanged in all 3 groups. However, the number of tender joints was significantly reduced for the EA and TCA groups. Physician’s global score was significantly reduced for the EA group and patient’s global score was significantly reduced for the TCA group. All the outcomes except patient’s global score remained unchanged in the Sham group. The researchers concluded that the pilot study allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn would help to clarify the existing evidence base on acupuncture for RA.|
Research on mechanisms for acupuncture
|He TF et al. Electroacupuncture inhibits inflammation reaction by upregulating vasoactive intestinal Peptide in rats with adjuvant-induced arthritis. Evid Based Complement Alternat Med 2011; 2011.|
|A study in rats that assessed the effects of electroacupuncture with adjuvant-induced arthritis. It was found to markedly decreased paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced body weight loss in an adjuvant-induced arthritis rat model. Electroacupuncture also resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP), a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was negatively correlated with the scores of inflammation in the synovial tissue (p=0.0026). The researchers concluded that their findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of rheumatoid arthritis, at least partially through the induction of VIP expression.|
|Ouyang BS et al. Effects of electroacupuncture and simple acupuncture on changes of IL-1, IL-4, IL-6 and IL-10 in peripheral blood and joint fluid in patients with rheumatoid arthritis. [Article in Chinese] Zhongguo Zhen Jiu 2010; 300: 840-4.|
A randomised controlled trial that explored the mechanism of acupuncture and electroacupuncture on rheumatoid arthritis (RA) in 63 patients. After 3 courses, changes of interleukins in peripheral blood and joint fluid of patients were observed. Both acupuncture and electroacupuncture had significant effects on interleukin (IL)-1, IL-4, IL-6 and IL-10 in the peripheral blood and joint fluid of patients with RA (p<0.05 and p 0 01 respectively). The researchers concluded that acupuncture and electroacupuncture can decrease the pro-inflammatory cytokines IL-1 and IL-6 and increase anti-inflammatory IL-4 and IL-10.
|Gao J et al. Involvement of the hypothalamus-pituitary-adrenal axis in moxibustion-induced changes of NF-kappaB signaling in the synovial tissue in rheumatic arthritic rats [Article in Chinese]. Zhen Ci Yan Jiu 2010; 35: 198-203.|
A study to observe the effect of moxibustion on the acupuncture points BL 23 and ST 36 on synovial nuclear factor (NF)-kappaB p65 expression, and plasma adrenocorticotropic hormone (ACTH) and serum cortisol (CS) contents in rats with rheumatoid arthritis (RA) with adrenalectomy (ADX). In comparison with the control group, the degree of swelling in the rats’ paws decreased significantly after moxibustion (p<0.01). compared with the model group serum cs contents and synovial nf-kappab p 65 immunoactivity in reduced moxibustion 0 01 05 The researchers concluded that moxibustion treatment can reduce inflammation reactions in rats with RA, which is closely associated with its effects in upregulating plasma ACTH, downregulating serum CS level and synovial NF-kappaB p 65 immunoactivity, and the intact hypothalamus-pituitary-adrenal axis (HPAA).
|He TF et al. Effects of acupuncture on the number and degranulation ratio of mast cells and expression of tryptase in synovium of rats with adjuvant arthritis [Article in Chinese]. Zhong Xi Yi Jie He Xue Bao 2010; 8: 670-7.|
A study that observed the effects of acupuncture on synovial pathology, synovial mast cell degranulation and tryptase expression and investigated the relationship between the functions of mast cells and effects of acupuncture on early adjuvant arthritis in rats. Compared with untreated rats, the body weight in the acupuncture group increased (p<0.05), while the paw volume decreased p 0 01 acupuncture inhibited inflammatory cell infiltration synovial hyperplasia and fibroplasia compared with no treatment 05 also it diminished numbers of total degranulated mast cells expression tryptase in synovium number degranulation ratio were positively correlated pathological scores. The researchers concluded that acupuncture can improve pathological conditions of inflammatory synovium in rats with early adjuvant arthritis by inhibiting the function of synovial mast cells.
|Hui KK et al. Acupuncture, the limbic system, and the anticorrelated networks of the brain. Auton Neurosci 2010; 157: 81-90.||A paper that discusses research showing that acupuncture mobilises the functionally anti-correlated networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response. The research used functional magnetic resonance imaging studies of healthy subjects to show that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. It has also been shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum.|
|Cheng KJ. Neuroanatomical basis of acupuncture treatment for some common illnesses. Acupunct Med2009;27: 61-4.|
|A review that looked at acupuncture treatment for some common conditions. It is found that, in many cases, the acupuncture points traditionally used have a neuroanatomical significance from the viewpoint of biomedicine. From this, the reviewers hypothesize that plausible mechanisms of action include intramuscular stimulation for treating muscular pain and nerve stimulation for treating neuropathies.|
|Komori M et al. Microcirculatory responses to acupuncture stimulation and phototherapy. Anesth Analg 2009; 108: 635-40.|
|Experimental study on rabbits in which acupuncture stimulation was directly observed to increase diameter and blood flow velocity of peripheral arterioles, enhancing local microcirculation.|
|Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008; 85: 355-75.||Review article that discusses the various peripheral and central nervous system components of acupuncture anaesthesia in detail.|
|Kavoussi B, Ross BE. The neuroimmune basis of anti-inflammatory acupuncture. Integr Cancer Ther 2007; 6: 251-7.|
|Review article that suggests the anti-inflammatory actions of traditional and electro-acupuncture are mediated by efferent vagus nerve activation and inflammatory macrophage deactivation.|
|Han JS. Acupuncture and endorphins.Neurosci Lett 2004; 361: 258-61.|
|A literature review of studies relating to the release of endorphins by acupuncture.|
|Zijlstra FJ et al. Anti-inflammatory actions of acupuncture. Mediators Inflamm 2003; 12: 59-69.|| |
An article that suggests a hypothesis for anti-inflammatory action of acupuncture: Insertion of acupuncture needles initially stimulates production of beta-endorphins, CGRP and substance P, leading to further stimulation of cytokines and NO. While high levels of CGRP have been shown to be pro-inflammatory, CGRP in low concentrations exerts potent anti-inflammatory actions. Therefore, a frequently applied ‘low-dose’ treatment of acupuncture could provoke a sustained release of CGRP with anti-inflammatory activity, without stimulation of pro-inflammatory cells.
|Pomeranz B. Scientific basis of acupuncture. In: Stux G, Pomeranz B, eds. Acupuncture Textbook and Atlas. Heidelberg: Springer-Verlag; 1987: 1-18.|
|Needle activation of A delta and C afferent nerve fibres in muscle sends signals to the spinal cord, where dynorphin and enkephalins are released. Afferent pathways continue to the midbrain, triggering excitatory and inhibitory mediators in spinal cord. Ensuing release of serotonin and norepinephrine onto the spinal cord leads to pain transmission being inhibited both pre- and postsynaptically in the spinothalamic tract. Finally, these signals reach the hypothalamus and pituitary, triggering release of adrenocorticotropic hormones and beta-endorphin.|