While currently prescribed analgesics are inadequate in addressing chemotherapy-induced peripheral neuropathy and may induce adverse side effects, nonpharmacologic remedies such as acupuncture may be promising candidates for treatment.
—Bahar Javdan, BA, and Ting Bao, MD, DABMA, MS
Acupuncture is a traditional Chinese medicine technique that involves inserting and manipulating filiform needles into specific points of the body to achieve a therapeutic effect. According to traditional Chinese medicine, disruptions in the flow of “vital energy” (qi) throughout the body are the underlying reason behind certain pathophysiologic conditions. Acupoints are defined as anatomic locations that promote the flow of qi to correct imbalance and regulate visceral function.
In the United States and internationally, acupuncture is used to relieve stress, enhance immunity and reduce insomnia, often combined with conventional medication for the management of cancer pain. In 1997, the National Institutes of Health formally acknowledged acupuncture’s ability to achieve therapeutic effects, including relieving pain and nausea.1,2
Although its precise mechanism of action has yet to be definitively elucidated, acupuncture’s therapeutic effects are thought to occur via multiple pathways, including neurohormonal changes and immunomodulation. Animal research suggests that acupuncture induces analgesia by stimulating nerves in muscles, which then relay the signals to the spinal cord, midbrain, and hypothalamus-pituitary system, ultimately triggering release of neurotransmitters and hormones such as endorphins and enkephalins.3 Animal and human studies suggest that acupuncture works by improving the availability and utilization of brain nerve growth factor.4 Acupuncture has been associated also with significant reduction in proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor (TNF)-α.5-10
Acupuncture points may be stimulated in various ways. With manual acupuncture, the filiform acupuncture needle is inserted in an acupuncture point and manually rotated to stimulate the point. With electroacupuncture, acupuncture points are stimulated by passing electrical current through inserted needles. Electrical current may be passed also through an electrode on the skin without inserting acupuncture needles, a technique called “noninvasive electrostimulation.” Acupressure is a form of acupuncture that uses only physical pressure with a finger or device such as an embedded stud in an elastic wrist band.
Acupuncture and acupuncture point stimulation are widely used as complementary therapies to treat a broad range of illnesses and symptoms and are frequently used by cancer patients. Growing evidence suggests that acupuncture is beneficial for the treatment of cancer pain and for chemotherapy-induced nausea and vomiting. It also appears to relieve symptoms such as radiotherapy-induced xerostomia, fatigue, hot flashes, depression, anxiety, and insomnia.
This article provides a synopsis of the role of acupuncture in alleviating cancer pain, with a special emphasis on acupuncture for chemotherapy-induced peripheral neuropathy.
Acupuncture for Cancer-Related Pain
Cancer pain is the most common and one of the most distressing and feared symptoms among cancer patients. It is estimated that up to two-thirds of patients with metastatic cancer suffer from cancer-related pain,11 and more than 75% of hospitalized oncology patients experience cancer-related pain.12-14 Due to its prevalence and importance, pain is often referred to as the “fifth vital sign” in oncology.
Cancer pain varies both by type of malignancy and by site of cancer involvement.15 The majority of cancer pain is caused by the direct effect of cancer as a result of visceral involvement, bony metastasis, soft-tissue invasion, or infiltration to the nerve or nerve plexus.16 Cancer treatments such as chemotherapy, radiation, and surgery also may induce cancer pain.17,18
Cancer pain typically is treated with opioids and with interventional anesthetic or neurosurgical procedures. Despite maximal use of pain medications and the application of interventional procedures, a significant portion of cancer patients still suffer from pain. In addition, the undesired side effects of long-term use of opioid pain medication, which include changes in mental status as well as constipation, nausea, and fear of dependency, are issues of concern. Consequently, cancer patients often turn to acupuncture and other complementary therapies for pain control.
Despite common use by oncology patients in efforts to control cancer pain, acupuncture has not been sufficiently documented via well-designed clinical trials. Many previous trials suffer from methodologic flaws such as poor study design, small sample size, and/or lack of appropriate data analysis.19 Consequently, two recent Cochrane systematic reviews of randomized controlled clinical trials showed no strong evidence for acupuncture’s effectiveness in reducing cancer pain.20,21 Another Cochrane systematic review assessed the value of transcutaneous electrical nerve stimulation in the management of cancer-related pain in adults; results were inconclusive due to a lack of suitable randomized controlled trials.22
Randomized Controlled Trials
Several recent, well-designed randomized controlled trials have studied the role of acupuncture in treating cancer pain. Summarized in Table 1,23-31 they include four trials that explored the efficacy of various types of acupuncture in controlling postoperative pain. Mixed results were found.
Deng et al’s study of 106 cancer patients experiencing post-thoracotomy pain showed no statistical difference between real vs sham acupuncture in patients’ pain scores as measured by the Brief Pain Inventory at 30, 60, and 90 days’ follow-up.23 The efficacy of the unique intradermal needles used in this study was questionable.
A smaller trial (N = 27) by Wong et al showed a trend of lower visual analog scale pain scores in patients receiving electroacupuncture compared with patients receiving sham acupuncture on postoperative days 2 and 6 and a statistically significant lower cumulative dose of patient-controlled analgesia on postoperative day 2 (P < .05).24 This study, however, was limited by its small sample size.
Mehling et al’s randomized controlled trial compared acupuncture plus massage therapy vs usual care in controlling postoperative pain, nausea, vomiting, and depressive moods in 93 cancer patients.25 It showed that postoperative acupuncture and massage in addition to usual care significantly improved pain control when compared to usual care alone.
Lastly, a study by Pfister et al showed that four weekly acupuncture treatments significantly reduced pain and improved function in cancer patients with chronic pain or dysfunction due to neck dissection, vs standard care alone.32 However, with no sham therapy group in the last two studies, it is difficult to tease out the placebo effect. It also leaves the question of whether professionally trained acupuncturists and massage therapists, as well as real vs sham acupuncture needles, are required for an intervention to succeed.
Chemotherapy-Induced Peripheral Neuropathy
A common side effect of chemotherapy, chemotherapy-induced peripheral neuropathy includes a variety of symptoms such as paresthesia, pain, and muscle weakness.33 Although the incidence of chemotherapy-induced peripheral neuropathy varies depending on the chemotherapy regimen and the duration of exposure, it is estimated to occur in approximately 38% of patients treated with multiple agents.34 The likelihood of developing the condition increases if the patient receives combinations of agents such as platinum drugs, vinca alkaloids, bortezomib (Velcade), or taxanes.35
Several characteristics of chemotherapy-induced peripheral neuropathy distinguish it from other forms of neuropathy such as carpal tunnel syndrome or metabolic neuropathy. Those diagnostic features include a symmetrical, distal, length-dependent “glove and stocking” distribution of the disorder, onset after administration of chemotherapy and progressive, dose-dependent continuation of chemotherapy, and predominantly sensory, rather than motor, symptoms.36 Nerve conduction studies have shown sensory axonal damage and reduced amplitude of sensory nerve action potential but unchanged motor nerve function throughout treatment.37
Chemotherapy-induced peripheral neuropathy can be serious enough to limit or delay the dose of administered chemotherapy and may warrant discontinuation of treatment. Long-term chemotherapy-related neuropathy often produces substantive functional decline and diminished quality of life.35,38
For patients with persistent chemotherapy-induced peripheral neuropathy, treatment may be limited to symptom management with narcotics, antidepressants, and antiepileptics.35 Studies suggest that analgesic regimens typically produce only modest relief of pain and other common side effects such as dizziness, sedation, dry mouth, and constipation.35 Antidepressants such as nortriptyline, and antiepileptics such as gabapentin and lamotrigine, may effectively reduce neuropathic symptoms associated with various conditions, not including chemotherapy-induced peripheral neuropathy.39-41
The only successful clinical trial for chemotherapy-related neuropathy treatment showed that the antidepressant duloxetine at 30 mg daily for 1 week followed by 60 mg daily for 4 more weeks caused a modest 1.06-point reduction in pain on a 10-point scale from baseline, compared with a 0.34-point reduction for placebo.42 However, duloxetine use was also associated with side effects, including fatigue and nausea, as well as a 12% dropout rate vs 1% for placebo.
The 2014 American Society of Clinical Oncology chemotherapy-induced peripheral neuropathy guidelines suggest a “moderate recommendation for treatment with duloxetine” and recommend further research in this area.33 Since there is currently no standard treatment for chemotherapy-induced peripheral neuropathy, new safe and effective treatments are needed.
Some relatively small studies have examined acupuncture’s ability to reduce the symptoms of chemotherapy-induced peripheral neuropathy. In a blinded randomized controlled trial, cancer patients with chronic peripheral or central neuropathic pain following cancer therapy were treated with auricular acupuncture. They experienced a 36% reduction in pain intensity vs a 2% reduction for sham-acupuncture–treated patients 2 months later (P < .0001).27
A case series of five patients suggested the potential efficacy of acupuncture in treating patients with chemotherapy-induced peripheral neuropathy.43 Another pilot study demonstrated that, among 11 patients with the disorder, 5 of 6 patients treated with acupuncture had improved nerve conduction vs only 1 of 5 patients who showed improvement in the control group.
In addition, objective nerve conduction studies demonstrated significant improvement with acupuncture approximately 3 months post intervention vs usual medical care.44 A positive correlation between improved chemotherapy-induced peripheral neuropathy and nerve conduction was found in 21 patients on acupuncture therapy vs 26 controls who received best medical care. A recent pilot study of 27 multiple myeloma patients with moderate to severe bortezomib-induced peripheral neuropathy demonstrated significantly reduced neuropathic pain and improved function following 10 weeks of acupuncture treatment.45
While currently prescribed analgesics are inadequate in addressing chemotherapy-induced peripheral neuropathy and may induce adverse side effects, nonpharmacologic remedies such as acupuncture may be promising candidates for treatment. The advantages of acupuncture include its low cost and minimal toxicity.
The preliminary research summarized here suggests that acupuncture may reduce chemotherapy-induced peripheral neuropathy symptoms, and that larger, more substantive randomized studies are warranted. Such studies should further evaluate acupuncture’s ability to reduce these symptoms and also should aim to elucidate the mechanism of action by which this effect occurs. ■
Disclosure: Dr. Bao and Ms. Javdan reported no potential conflicts of interest.
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Ms. Javdan, a recent graduate of the University of Pennsylvania, is spending her gap year prior to MD/PhD training in research with the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York. Dr. Bao is a breast medical oncologist in the Integrative Medicine Service at Memorial Sloan Kettering.
Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan Kettering Cancer Center, New York.
The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective information about herbs, vitamins, minerals, and other dietary supplements and unproved anticancer treatments. Each of the close to 300 and growing number of entries offer health-care professional and patient versions, and entries are regularly updated with the latest research findings.
In addition, the About Herbs app, Memorial Sloan Kettering Cancer Center’s very first mobile application, can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8. The app is compatible with iPad, iPhone, and iPod Touch devices.