Acupuncture and Pain:
Applying Modern Science to an Ancient Practice

By NATIONAL INSTITUTES OF HEALTH • NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE

Qi, meridians, yin, yang. How can researchers study acupuncture, a 2,000-year-old form of traditional Chinese medicine (TCM) based on foreign concepts that seem impossible to measure, let alone define?

To Richard Nahin, Ph.D., M.P.H., NCCAM's Senior Advisor for Scientific Coordination and Outreach, the answer is obvious: "We don't necessarily have to understand the concepts of qi or meridians to study the safety or efficacy of acupuncture."

Harvard Medical School neuroscientist (and practicing acupuncturist) Vitaly Napadow, Ph.D., L.Ac., agrees. "I firmly believe that everything can be studied with the scientific method. Unfortunately, we don't currently have a 'qi meter.' So, in my research, we don't focus on meridians or qi. We take a neuroscientific approach to study how acupuncture functions through the nervous system."

Using the latest technologies in neuroimaging and genomics, Dr. Napadow and other NCCAM-supported scientists are drawing a scientifically coherent picture of how acupuncture affects the body. They can see physiological effects—changes in the brain's pain centers—with acupuncture. They've observed gene expression and molecular changes in the nervous and immune systems. They hope one day to be able to predict which patients are most likely to benefit from acupuncture.

Scientists aren't ready to claim that acupuncture works for any specific disease—yet. But NCCAM-supported studies have yielded promising evidence that this ancient practice modifies perception of pain and its processing by the brain, and that it may be helpful for pain management. In the years since the 1997 National Institutes of Health consensus statement on acupuncture concluded that more rigorous research was needed, NCCAM has supported a substantial body of research. A number of these studies have tackled the challenge of developing trial designs needed to answer practical clinical questions.

Acupuncture involves stimulating points on the body, using thin, solid, metallic needles that are manipulated by hand or by electrical stimulation. Chinese tradition teaches acupuncture practitioners that the aim is to improve levels of qi, which is considered the energy force behind all life, and restore balance in the opposing forces of yin and yang. The needles are placed along meridians, invisible energy channels described in ancient Chinese manuscripts as running the length of the body.

Building an Evidence Base: Clinical Research Progress

"Our goal is to build a house of evidence," explains long-time NCCAM grantee Brian Berman, M.D., director of the Center for Integrative Medicine at the University of Maryland School of Medicine.

To date, much of the progress in clinical research on acupuncture has come from an interdisciplinary approach that includes experts in acupuncture, clinical trial methodology, biostatistics, and relevant diseases such as osteoarthritis or carpal tunnel syndrome.

"What we've learned so far is that the most promising area for using acupuncture is pain," says Dr. Nahin. Clinical studies are showing acupuncture's efficacy for some types of pain, such as back, osteoarthritis, and postoperative pain. For example, a systematic review supports the use of acupuncture for postoperative pain management. An NCCAM-supported Phase III clinical trial led by Dr. Berman showed that acupuncture relieved pain and improved function in patients with knee osteoarthritis when it was used with standard medical care, including anti-inflammatory medications and opioid pain relievers. In a large study published in 2009, researchers found that people suffering from chronic low-back pain who received acupuncture or simulated acupuncture treatments fared better than those receiving only conventional care. Pilot studies have looked at acupuncture in posttraumatic stress disorder and chemotherapy-induced nausea and vomiting. And, the Cochrane Collaboration reviewed 11 randomized trials and found that acupuncture may be a valuable option for patients suffering from tension headaches.

But these clinical outcomes may involve more than acupoints and needles. Other aspects of the acupuncture experience may play important roles in healing, including reassurance provided by the practitioner, expectation of benefit, and the sensory experience elicited by acupuncture needling, which has been called de qi and variously described as aching, dull pain, tingling, or a heaviness. In several recent studies researchers have carefully designed their studies to compare true acupuncture to simulated acupuncture and have tried to mimic the sensory experience of true acupuncture so that patients would be unaware of whether they were receiving true or simulated acupuncture. In some of these studies, such as the 2009 study on low-back pain, both simulated acupuncture and real acupuncture produced greater benefit than standard therapy.

Acupuncture's Effect on the Brain

Fascinating results regarding the possible use of acupuncture are coming out of clinical trials, but what are the mechanisms of action behind these effects? For example, NCCAM-supported researchers are tapping into the power of genomic techniques to look at what is happening at the cellular level and study acupuncture's effect in the expression of genes involved in pain. Researchers are also harnessing cutting-edge technologies to uncover pathways in the brain involved in the body's response to acupuncture.

"We wanted to know if the brain was involved in the process and how it was involved," says Bruce Rosen, M.D., Ph.D., principal investigator of an NCCAM Center of Excellence on Acupuncture and Brain Activity at Harvard Medical School. And the time is right to approach these questions. Powerful imaging techniques—fMRI (functional magnetic resonance imaging), PET (positron emission tomography), and MEG (magnetoencephalography)—are now available to reveal areas of the brain affected during pain and to map the impact of acupuncture in patients experiencing pain.

"With the advent of noninvasive brain imaging we were able to begin looking at human brain response to acupuncture and start to evaluate potential mechanisms in humans," says Dr. Napadow. And they found differences in this brain response between people with chronic pain and healthy controls.

For example, in research on carpal tunnel syndrome, which can cause pain and numbness due to compression of nerves in the wrist, Dr. Napadow and colleagues performed fMRI before and after acupuncture and found that patients with carpal tunnel syndrome responded to acupuncture differently from healthy controls. Their studies, published in 2007, showed that the brain of patients with carpal tunnel syndrome responded to acupuncture needling with greater activation in an area of the brain known as the hypothalamus and deactivation in another area known as the amygdala. These two areas of the brain are involved in behavior, emotions, long-term memory, and maintenance of a persistent pain state.

A number of aspects of the acupuncture experience probably contribute to the neural effects and quite possibly to the clinical benefit. Researchers have learned that the direct effects of acupuncture may be amplified by the expectation of benefit. "We found that expectation itself is a powerful modulator of the brain," says Dr. Rosen. "Expectation seems to be as powerful an influence on reduction in pain as acupuncture needling, though it appears to work in a different network in the brain that may be complementary."

Next-Generation Studies

While researchers continue to tackle the challenges in conducting acupuncture studies, such as differences between Western and TCM diagnostic approaches, acupuncture's focus on individualized care, and finding the best possible simulated or placebo procedure, they are also working toward the next generation of studies.

"We want definitive information for health care providers and the public on when acupuncture should be used and for whom, and what types and course of therapy will show efficacy," says NCCAM's Dr. Nahin. "We want to know the most appropriate dose, how many treatments per week, and what needle points are effective so acupuncturists can use evidence-based medicine to give the best care to their patients."

Researchers would also like to know if adjuvant acupuncture could enable reduction in doses of pain medications, with fewer adverse effects of the medication.

Finally, having a test to know who would benefit from acupuncture would be a move toward personalized medicine. Researchers are using imaging studies and genomic studies to search for biomarkers to predict who would be good candidates for acupuncture. "Now we can embed brain imaging evaluation within a clinical trial to correlate clinical outcome measures with brain changes," says Dr. Napadow.

"There's something about the specifics of acupuncture that seem to evoke a more dramatic response in certain parts of the brain than other kinds of sensory stimuli," Dr. Rosen says. "It suggests there's something special about acupuncture that's worth trying to understand."

Progress on Pain

NCCAM-supported studies are revealing how and when acupuncture works, such as the neurological effects of stimulation with acupuncture needles and the role expectation can play in pain.

Patients who are experiencing chronic pain show different brain changes from those of healthy volunteers, an important finding for understanding overall pain processes, as well as acupuncture's effects.
Acupuncture appears to affect several mechanisms in the brain and spinal cord, including those involved in pain and inflammation.
Expectation of pain relief plays a role in acupuncture's impact, although it affects an area of the brain that tells the body how to deal with pain, rather than the pain-reducing areas affected by needle stimulation itself.

For more information on acupuncture for pain, see this issue's interview column.

References

Allen JJ, Schnyer RN, Chambers AS, et al. Acupuncture for depression: a randomized controlled trial. Journal of Clinical Psychiatry. 2006;67(11):1665–1673.
Berman BM, Lao L, Langenberg P, et al. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Annals of Internal Medicine. 2004;141(12):901–910.
Cherkin DC, Sherman KJ, Avins AL, et al. A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain. Archives of Internal Medicine. 2009;169(9):858–866.
Ezzo J, Richardson MA, Vickers A, et al. Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting. Cochrane Database of Systematic Reviews. 2006(2):CD002285.
Hollifield M, Sinclair-Lian N, Warner TD, et al. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial. Journal of Nervous and Mental Disease. 2007;195(6):504–513.
Kelley JM, Lembo AJ, Ablon JS, et al. Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosomatic Medicine. 2009;71(7):789–797.
Kong J, Gollub RL, Webb JM, et al. Test-retest study of fMRI signal change evoked by electro-acupuncture stimulation. NeuroImage. 2007;34(3):1171–1181.
Kong J, Kaptchuk TJ, Polich G, et al. Expectancy and treatment interactions: a dissociation between acupuncture analgesia and expectancy evoked placebo analgesia. NeuroImage. 2009;45(3):940–949.
Linde K, Allais G, Brinkhaus B, et al. Acupuncture for tension-type headache. Cochrane Database of Systematic Reviews. 2009(1):CD007587.
Napadow V, Kettner N, Liu J, et al. Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome. Pain. 2007;130(3):254–266.
Napadow V, Kettner N, Ryan A, et al. Somatosensory cortical plasticity in carpal tunnel syndrome—a cross-sectional fMRI evaluation.NeuroImage. 2006;31(2):520–530.
Napadow V, Liu J, Li M, et al. Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture. Human Brain Mapping. 2007;28(3):159–171.
Sun Y, Gan TJ, Dubose JW, et al. Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials. British Journal of Anaesthesia. 2008;101(2):151–160.