**2. Acupuncture for rheumatoid arthritis**

#### **2.1 Acupuncture therapeutics**

Acupuncture, originating in China more than 3,000 years ago, is one of the most popular sensory stimulation therapies. It is an ancient technique of inserting and manipulating fine needles to stimulate specific anatomic points, also known as acupuncture points or meridian points. There have been extensive investigations into the biological mechanisms of acupuncture (Cho et al., 1998; Darras et al., 1992; Dhond et al., 2008; Gao et al., 1997; Han & Terenius, 1982; Han, 1997; Harris et al., 2009; Hui et al., 2000; Hui et al., 2005; Kaptchuk, 2002; Kovacs et al., 1992; Langevin et al., 2001a; Langevin et al., 2001b; Langevin et al., 2007; Li et al., 2007; Napadow et al., 2005; Napadow et al., 2007; Napadow et al., 2008; Pariente et al., 2005; Wu et al., 1999; Zhang et al., 2005). Some of the best evidence is in relation to treatment of pain. Three previous systematic reviews examined the efficacy of acupuncture in patients with rheumatoid arthritis and reported that acupuncture has conflicting evidence for treatment of RA in the placebo-controlled trials (Casimiro et al., 2005; Lee et al., 2008; Wang et al., 2008a). Another narrative review examined 63 Chinese studies with a variation of acupuncture therapies in patients with rheumatoid arthritis and concluded that acupuncture is helpful for rheumatoid arthritis (Suzuki et al., 2005). However, in addition to the complexities revealed by an evaluation of this sort of intervention, many of these prior studies have methodological concerns that limit their interpretation. Therefore, this section performs an updated review of all currently available data, including Chinese publications.

#### **2.2 Clinical evidence**

Explanatory mechanisms from eastern and western biological theory provide a supposed rationale for the effectiveness of acupuncture to treat the chronic inflammatory nature of rheumatoid arthritis (Han et al., 1986; Han, 2004; Wang et al., 1985; Zijlstra et al., 2003). Considerable evidence has shown that acupuncture analgesia may be imitated by stimulation of nerves, which, in turn, trigger endogenous opioid mechanisms. Recent functional magnetic resonance imaging studies also demonstrated that acupuncture has regionally specific, quantifiable effects on relevant structures of the human brain (Hsieh et al., 2001; Hui et al., 2000; Napadow et al., 2005; Pariente et al., 2005; Wu et al., 1999; Yoo et al., 2004). However, clinical research into the effects of acupuncture on chronic pain is challenged by methodological concerns, including finding appropriate inactive controls. For example, the larger literature on clinical trials of acupuncture on pain has failed to show a significant improvement over sham acupuncture (Brinkhaus et al., 2006; Linde et al., 2006; Melchart et al., 2005). Indeed, there are troublesome findings of non-superiority of acupuncture over shams.

To update the current clinical evidence regarding the effects of acupuncture on rheumatoid arthritis, a comprehensive search of 10 western and Chinese databases and reference lists was performed based on our previous work (Wang et al., 2008a). The review included clinical trials with pain as an endpoint being measured by tender joint count or a pain scale. The effects of acupuncture on morning stiffness, erythrocyte sedimentation rate and Creactive protein were also reported. Nine studies met eligibility criteria with a total of 597 subjects. There were 4 placebo-controlled trials and 5 active-controlled trials (**Table 1**). The average study duration was 11 weeks. Mean (SD) numbers of acupuncture points and sessions were 11 (8) and 42 (62), respectively. The average duration of needle insertion was 24 minutes. Eight trials used traditional acupuncture (TA) (Cui et al., 2001; David et al., 1999; Jiang & Fan, 2003; Liu et al., 2003; Tam et al., 2007; Wang, 2002; Zanette Sde et al., 2008; Zhou & Zhu, 2000), two used electroacupuncture, (EA) (Man & Baragar, 1974; Tam et al., 2007) and one used both (Tam et al., 2007). Four trials used placebo needles (sham acupuncture orincorrectly placed needles) as the control (David et al., 1999; Man & Baragar, 1974; Tam et al., 2007; Zanette Sde et al., 2008). The other five studies published in China used a variety of active interventions in the control groups, including methotrexate, topical Votalin ointment, and non-steroidal anti-inflammatory drugs.
