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9 Articles in Volume 9, Issue #2
Acupuncture for Fibromyalgia
Brain Atrophy with Chronic Pain: A Call for Enhanced Treatment
Evaluating Function/Impairment of Low Back Pain Using SEMG
Medication-induced Xerostomia Secondary to Pain Management
Neuroscience, Neurophilosophy, and Neuroethics of Pain, Pain Care, and Policy (N3P3)
Reducing Pain and Anxiety During Reduction of a Fracture
Successful Treatment of Intractable Pain
Treating Chronic Pain by Patient Empowerment
Treatment of Scapulohumeral Periarthritis and Post-traumatic Joint Pain

Acupuncture for Fibromyalgia

Acupuncture may be a useful intervention to manage chronic pain of fibromyalgia.

Dr. Richard Harris has written a compelling article regarding the successful use of acupuncture in treating chronic pain in both fibromyalgia and other conditions. Since most fibromyalgia experts agree that a multidisciplinary treatment approach is most effective in reducing FM symptoms, it seems logical based on Dr. Harris’s observations that adding acupuncture to such a program would help decrease pain in many FM patients.

Acupuncture, as a therapeutic modality, has been used for at least two thousand years in China and is now being practiced with increasing frequency within Western countries. Although patients seek out this intervention for a variety of ailments, the scientific research community has yet to understand, from an experimental perspective, what the specific mechanisms of acupuncture are. For example, two acupuncture trials in fibromyalgia (FM) suggest that acupuncture needling produces more analgesia than sham acupuncture,1,2 yet conflicting data has arisen from two other clinical trials of acupuncture in FM that suggest that acupuncture is not efficacious when compared to sham.3,4 Similar mixed findings can be found for other chronic pain conditions.5-7 Regardless, acupuncture continues to be used widely by the public and it also appears to be cost-effective when compared to usual care.8,9 Given these data, one could ask, “Is there a specific physiological effect of acupuncture that is distinct from the placebo effect?” and “Should acupuncture be offered as a viable treatment option for some conditions—particularly those that are troublesome for conventional Western healthcare?”

In this article, I highlight some of the mechanistic factors involved in acupuncture analgesia—from both a Western medical perspective as well as a Traditional Chinese Medical perspective. I also explore the potential meaning underlying the findings from randomized controlled clinical trials of acupuncture in FM. Finally, I propose that since acupuncture is safe, effective (if not efficacious), and cost saving, it should be considered as a useful intervention in the treatment of complex pain syndromes.

Background

Acupuncture has been used as a therapeutic intervention for over two thousand years in Asia and remains an important facet of the modern Chinese medical system. The use of acupuncture as an alternative form of medicine in Western countries including the U.S. has increased over the past century and has expanded rapidly over the last three decades. Acupuncture has been used by millions of Americans and is performed by thousands of health care providers. The FDA estimates that Americans spend half a billion dollars a year on acupuncture treatments to deal with a variety syndromes. In 1996, after reviewing the existing body of knowledge, the FDA removed acupuncture needles from the category of “investigational and experimental medical devices” and now regulates them in the same manner as other medical devices—such as surgical scalpels and hypodermic syringes—under good manufacturing practices and single-use standards of sterility.10

Although no uniformly accepted definition is currently available, the 1997 Acupuncture-NIH Consensus Development Statement characterizes acupuncture as follows: “Acupuncture describes a family of procedures involving stimulation of anatomical locations on the skin by a variety of techniques. In most studies, the mechanism of stimulation of acupuncture points employs penetration of the skin by thin, solid, metallic needles, which are manipulated manually or by electrical stimulation. Stimulation of these areas by moxibustion, pressure, heat, and lasers is used in acupuncture practice but, due to the paucity of studies, these techniques are less easy to evaluate. Thus, there are a variety of approaches to diagnosis and treatment that incorporate medical traditions from China, Japan, Korea, and other countries.”10

This working definition tells us that acupuncture is heterogeneous, with differing medical traditions and practices being recognized. The traditional therapeutic intervention with acupuncture is frequently administered in a holistic setting that includes an initial evaluation or assessment of the underlying problems and may be combined with dietary, herbal, and/or pharmacological interventions. It is important to note that the scientific investigation of acupuncture to date has largely evaluated only limited facets of the clinical practice of acupuncture.

In 2007, a landmark scientific conference was held by the Society for Acupuncture Research. This conference was held as a 10-year anniversary of the NIH 1997 Acupuncture-NIH Consensus meeting and the event was funded by the NIH/National Center for Complementary and Alternative Medicine and numerous acupuncture schools and organizations. This event—attended by 300 practitioners, scientists, and students originating from eight countries—discussed acupuncture research in both general and disorder-specific contexts. The data that was presented summarized acupuncture findings from the basic research setting as well as clinical trial perspectives.11-13 Overall, there was consensus that acupuncture elicited specific changes in biologic outcomes when examined from a physiological perspective, however clinical trial outcomes were less positive. While acupuncture was widely accepted to be superior to no treatment or standard of care, multiple randomized controlled clinical trials failed to show that acupuncture was superior to sham treatment. Therefore in many of the large randomized controlled trials for chronic pain,5-7 acupuncture was considered to be effective but not efficacious (see below).

Traditional Theories of Acupuncture

The traditional theoretical bases for the major schools of acupuncture—namely Chinese, Japanese, Korean and French—are both varied and complex.14,15 The theories are based on the medical traditions of these countries and have evolved over millennia of clinical use and experience and have only recently been the subject of western scientific investigation.

The concepts of Traditional Chinese Medicine (TCM) have greatly influenced the theoretical basis for acupuncture, regardless of the particular school. Classical acupuncture is based on key traditional Eastern medical concepts such as the circulation of Qi and the meridian system.10,15 The theory states that vital energy (i.e. Qi) flows along well-defined channels, meridians, or collaterals. The state of a person’s health and well being is dependent on the balance of this vital energy in the system and the overall level of energy.16 Symptoms and ill health are defined in terms of an imbalance in vital energy between organs and sub-organ systems. Acupuncture incorporates the insertion of needles at well-defined sites located on the channels and the needles are then manipulated with the goal of restoring or adjusting the energy flow to a state of balance and returning the patient to a state of good health. Regardless of the differing theoretical bases, the stimulation of needles that have been placed in well-defined sites on the body is a recurring theme in acupuncture practices throughout the world.

Conventional Theories

The traditional theory of acupuncture has increasingly been the subject of Western scientific investigation.3,4,17 However, Western medicine has not discovered a neuroanatomic correlation for channels or meridians. Nor does medical physiology identify a correlate to the concept of vital energy, or Qi. In the absence of methods to define channels, meridians, or points to quantify Qi, the testing of traditional acupuncture theory by standard methods of Western scientific inquiry remains problematic.

Studies have focused on the mechanisms of acupuncture-mediated analgesic effects and have been reviewed in detail.18,19 The importance of the sensation “De Qi” in response to the needle stimulation has been emphasized to produce a positive therapeutic response. This sensation is described as a sensation of numbness, tingling, achiness, or heaviness. It appears as though this sensation is evoked by activation of somatosensory nerves in the muscles below acupuncture needle sites rather than the skin or subcutaneous tissue. Pomeranz19 has suggested that one set of sensory nerves is responsible for the transmission of the sensation of numbness or tingling, while the achiness or heavy sensation is transmitted by a different set. What do these sensations mean for acupuncture’s efficacy and mechanism?

Functional magnetic resonance imaging (fMRI) studies suggest that different brain regions may be activated or deactivated during “De Qi” sensations as opposed to tactile stimulation.20 Multiple areas in the limbic system seem to be deactivated with needle stimulation (see below). However, we do not understand how these neuronal changes can result in pain relief. For example, the analgesic effect of acupuncture arises within 30 minutes following needle manipulation21 which is much later than effects measured in fMRI. In addition, multiple clinical trials demonstrate that sustained effects of acupuncture can persist for weeks to months following needle removal.5,7,22 The investigation of the molecular determinants of these more persistent analgesic effects, as well as those that arise in the tens of minutes, is lacking in mechanistic human acupuncture clinical trials. These effects may be important and are possibly the most clinically relevant outcomes for acupuncture.

Acupuncture Treatment in FM

There have been four well-executed randomized controlled trials of acupuncture in FM.1-4 These trials used differing acupuncture methods and, not surprisingly, obtained differing results. Deluze et al randomized 70 FM patients to receive either electroacupuncture or sham electrical stimulation and found improvement in seven of eight outcome measures in the active treatment group, whereas none were improved in the sham group.1 In a more recent trial, Martin et al randomized 25 FM patients to receive electro-acupuncture and 25 to sham acupuncture and found significantly greater pain reduction in the acupuncture group as compared to sham.2

However, two larger trials found similar efficacy of acupuncture to sham in FM. Harris et al compared correct acupuncture needle placement and stimulation to incorrect placement and found no difference between methods.3 Assefi et al used acupuncture with no manual manipulation as the active group and had control groups where 1) needles were placed in non-acupuncture points or 2) a non-insertion sham needle was used.4 She found no differences between groups, even when the skin was not penetrated with a needle.

Thus, clinical trials of acupuncture in FM have had mixed findings. However, acupuncture may be engendering a strong analgesic response, given the high response rates observed in these trials, even the negative ones. For example, 25-35% of individuals in these trials received clinically relevant reductions in their pain symptoms following acupuncture. This is as large as the percentage of responders observed in clinical trials of pregabalin23 and duloxetine,24 two medications approved by the Food and Drug Administration for FM. It is interesting to note that the analgesic effects of acupuncture in these studies is somewhat larger than the responses to placebo pills administered in recent drug trials of FM.23,25,26 A logical question to ask is, “Does acupuncture result in enhanced placebo effects?”

The Placebo Effect

Attempts to address acupuncture from a Western scientific approach have received critique that acupuncture is largely a “placebo effect.”27 Indeed as mentioned above, some acupuncture trials have discovered that pain relief is no better when needles are placed in control locations as opposed to traditional acupuncture points. However this may reflect an artifact of trial design and the clinical research setting. For example, factors such as “regression to the mean” likely account for a high proportion of what is often termed a “placebo effect” (i.e. improvement in the group not receiving an active intervention) in the above trials of acupuncture. Just as in clinical practice, acupuncturists in clinical trials may form dialog and relationships with patients and this may provide a therapeutic effect. Furthermore, belief systems of either the acupuncturist or the patient may also play a role in the magnitude of placebo effect. All of these factors are operative in both participants receiving active and sham acupuncture in clinical trials and may obscure, or at least render it difficult to detect, a specific neurobiological effect that only occurs with active and not sham acupuncture. Neurobiological effects are also expected to be present because there is now substantial data suggesting that acupuncture engenders analgesic effects even in animal models of pain.28-33 In this setting, differences in patient/practitioner beliefs and/or the environment of the clinical research setting are presumably absent, suggesting that these more cognitive factors may not be the only factors engendering acupuncture analgesia.

Current techniques used to control for “non-specific” or “placebo effects” in acupuncture research include: 1) a retractable blunt needle34 or 2) a sharp pricking instrument.35 These instruments do not penetrate the skin and are thus proposed to separate effects of needle insertion from the above mentioned psychological and environmental factors. The retractable needle is similar to a stage dagger and does not require participants to be blindfolded during treatment. The sharp pricking device that mimics needle insertion has been used previously and requires a blindfold or mask so that participants cannot see that needles have not been inserted. With the advent of these more modern control groups, differentiation of the psychological effects resulting from patient/practitioner interactions from more physiological mechanisms of needle insertion, if present, may be obtained.

“Research over the last four decades has demonstrated that a significant component of acupuncture analgesia is thought to involve the release of endogenous opioids from neurons within the central nervous system.”44-47

One complicating issue with respect to the concept of the “placebo effect” is that all placebos may not be created equal. In a recent study of arm pain, investigators compared two different sham interventions: a placebo pill and sham acupuncture. Surprisingly, sham acupuncture was more effective at reducing arm pain than a placebo pill.36 If this finding is replicated by other groups, it would confirm a long held belief in the placebo field that not all placebos are created equal. Many have speculated that because sham surgery is more invasive it may engender a stronger “placebo effect” than less invasive control groups such as taking a sugar pill. This has implications for the field of acupuncture. Sham acupuncture may not be an inert intervention. If true, this would imply that the randomized controlled clinical trials of acupuncture in chronic pain states may have been “negative” due to an active control comparison group—thus reducing the effect size of acupuncture. In these cases, acupuncture is being compared to a effective analgesic.

Brain Imaging: Functional Magnetic Resonance Imaging (fMRI) in Acupuncture

One approach to differentiate acupuncture effects from the “placebo effect” is to investigate the underlying neural substrates of both processes. Recent investigations have focused on examining brain activity in response to needle insertion and manipulation. To date, multiple functional magnetic resonance imaging (fMRI) studies have addressed this issue.20,37-40 Zhang et al have shown that needle stimulation at different frequencies can produce differential changes in brain activity.32 Two studies by Hui and Napadow have shown that acupuncture needle stimulation engenders a decrease in the fMRI Blood Oxygenation Level Dependent (BOLD) signal within the limbic system and the cerebellum.38,39 These investigations clearly differentiate acupuncture needling effects from sham stimulation, emphasizing the point that needle insertion into the body has physiological effects on the brain that are different from placebo effects.

However most studies to date have focused primarily on healthy normal controls and have not examined chronic pain populations (but see refs. 41,42). Furthermore, the changes in brain activity observed using fMRI block designs are not sustained and cease when needle manipulation stops. Clinical experience indicates that analgesia resulting from acupuncture often persists for weeks to months after needles have been removed.5-7,22,43 Thus the majority of neuroimaging studies performed to date do not address the issue of how acupuncture would work to treat chronic or sustained pain.

Endogenous Opioids and Acupuncture

Research over the last four decades has demonstrated that a significant component of acupuncture analgesia is thought to involve the release of endogenous opioids from neurons within the central nervous system.44-47 The release of these neurotransmitters within the synapse is thought to subsequently activate opioid receptors.48 Activation of these receptors and, in particular, the µ type is thought to result in both pre- and post-synaptic neuronal inhibition which reduces the sensation of pain.49,50

Interestingly, the activation of central µ-opioid receptors (MORs) has also been implicated in the “placebo effect.”51 Since multiple large-scale randomized controlled clinical trials of acupuncture in different chronic pain conditions have demonstrated similar analgesic effects following both traditional and sham acupuncture therapy (see above), acupuncture effects on opioidergic neuronal pathways may be partly shared with those activated during placebo administration. This seems feasible since, under conditions of expectation of analgesia, the administration of a placebo induces the activation of µ-opioid receptors in pain regulatory regions.47,51-54

As mentioned above, recent functional neuroimaging studies demonstrate that during acupuncture needle stimulation, limbic structures—including the amygdala, the hippocampus, and the perigenual cingulated—appear to be deactivated via a mechanism that is distinct from pain and from that seen with sham stimulation.37,38,55 Thus, paradoxically, traditional acupuncture and sham acupuncture therapy may have equivalent analgesic effects yet they evoke divergent neurobiological consequences.

Another potential explanation for the largely negative trials of acupuncture in chronic pain conditions is that the disorders themselves render patients to respond less well to the intervention. For example, multiple neuroimaging studies in chronic pain patients have demonstrated reduced opioid receptor binding ability at locations within the brain known to process or modulate pain. One study by our group in FM56 and two additional ones in other chronic pain states (rheumatoid arthritis57 and central neuropathic pain following stroke58,59) found a reduction in opioid receptor binding potential within the brain. In the case of FM, the reductions in MOR binding potential observed were localized in regions known to be involved in antinociception in animal models,60,61 as well as pain and emotion regulation—including the affective quality of pain—in humans62-64 (i.e., dorsal anterior cingulate, nucleus accumbens, amygdala).

These effects may have repercussions on the efficacy of acupuncture. For example, if chronic pain patients have an activated opioid receptor system pre-treatment—as evidenced by reduced receptor binding availability—they may therefore be less likely to respond to an intervention like acupuncture that is thought to increase release of endogenous opioids. The receptors in the chronic pain patients may already be maximally occupied by the endogenous opioids. Alternatively, the reduced receptor binding availability may be indicative of fewer numbers of the receptors available to bind the ligand. This too would result in a reduced analgesic effect of released endogenous opioids. Either way, chronic pain patients may have a reduced effect of acupuncture.

Cost-Effectiveness of Acupuncture

Regardless of the potential mechanisms of action of acupuncture, the potential usefulness of this intervention in the United States health care system is demonstrated by recent trials suggesting the cost-effectiveness of acupuncture. The equipment needed to perform acupuncture is quite minimal. The basic materials needed are needles, isopropyl alcohol, cotton balls, and a biohazard container to dispose of the needles. The cost of typical acupuncture needles range in price from $3.00- $11.00 per box (with typically 100 needles per box), with the average acupuncture treatment using 8-20 needles. This results in an estimated equipment cost of less than $2.20 per session. The fee for the acupuncturist is the major expense and this can range from $60-$100 per treatment session. Since the effects of acupuncture tend to be cumulative and lasting, with sustained symptom relief for weeks to months following treatment,5-7 costs from the initial treatments may be counterbalanced by lasting treatment effects. Because some prescription medications have side effects—for example, commonly prescribed nonsteroidal antiinflammatory drugs can cause internal gastrointestinal bleeding—patients may be driven to seek additional health care and so acupuncture may be a cost-effective option. Two recent studies demonstrate the cost-effectiveness of acupuncture in chronic headache pain and osteoarthritis when compared to standard of care.65,66

Conclusions

Acupuncture has specific biological effects in both animal and human pain conditions however the clinical effects of acupuncture needling tend to be no better than sham acupuncture. While acupuncture is typically better than no treatment or wait list control groups, it generally is no better than sham therapy. That said, it is possible that the mechanisms of action of acupuncture may be fundamentally different than the “placebo effect.” Despite the fact that both may rely on endogenous opioids, multiple fMRI studies have illustrated divergent mechanisms for acupuncture and sham treatment. Perhaps, most importantly, acupuncture appears to be a cost-effective treatment when compared to standard of care. Is it right to reject a safe, effective, and cost-saving treatment option especially for conditions that are poorly managed by the existing health care system? Future studies may provide more insights into this question and may also stimulate the movement of acupuncture into more conventional care settings.

Disclosure

Funding for this article came from Department of Army grant DAMD-Award Number W81XWH-07-2-0050.

Last updated on: April 26, 2012
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