By Traci Pantuso, ND, MS
Adjunct Faculty, Bastyr University, Seattle; Owner, Naturopathic Doctor Harbor Integrative Medicine, Bellingham, WA
Dr. Pantuso reports no financial relationships relevant to this field of study.
- Individuals suffering with migraine often use complementary and integrative therapies to treat migraine symptoms.
- Acupuncture has moderate evidence in reducing the frequency of migraine attacks.
- Neuromodulation is a promising treatment on the horizon for those suffering with migraine.
Migraine is a common recurrent neurological disorder that affects 36 million Americans and is estimated to cost $13 billion a year because of decreased productivity and increased healthcare utilization.1 The estimated one-year prevalence of migraine is 18% for women and 6% for men in the United States,2,3 and migraine is the sixth most common diagnosis worldwide.4
Migraine is a complex brain network disorder that involves multiple cortical, subcortical, and brainstem regions. The pathogenesis of migraine has yet to be fully elucidated. Genetic and environmental factors appear to play a role in the susceptibility to migraine, and genome-wide association studies have identified some candidate genes.5 It is estimated that individuals with a family history are three times more likely to have migraines themselves,6 and another study found that 40-50% of an individual’s susceptibility is inherited.7 Historically, migraine was thought to be caused primarily by vascular changes; however, research over the last decade has demonstrated involvement between both neuronal and vascular components.8
The generation of pain in migraine headache is thought to involve meningeal afferents, neuropeptide release, and neurogenic inflammation.9 Cortical spreading depression theory links the migraine aura with the headache and is defined as the self-propagating wave of neuronal depolarization that spreads across the cerebral cortex.10 It is believed that the cortical spreading depression causes the migraine aura and activates the trigeminal nerve afferents, which lead to neurogenic inflammation. Neurogenic inflammation is the result of stimulation of the trigeminal ganglion, which then releases vasoactive neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinin A.9 The two main processes of neurogenic inflammation are plasma protein expression and vasodilation caused in part by CGRP. Neurogenic inflammation may be the cause of sensitization leading to the neurons becoming increasingly responsive to painful and non-painful stimulation.9
Migraine symptoms include moderate to severe unilateral head pain that may have a pulsating quality that lasts between four and 72 hours with any number of associated symptoms of photophobia, phonophobia, nausea, and vomiting.11
The head pain may be accompanied or preceded by an aura that may have sensory, motor, or language symptoms.11 Migraine can be described as an episodic migraine or chronic migraine, depending on the number of days per month with migraine. Episodic migraine is classified as less than 15 days with migrainous headaches per month, while chronic migrainous headaches occur more than 15 days per month.11 Treatment options in the prevention of migraine include various medications such as beta-blockers, calcium channel blockers, and various psychotropics, with reported response rates of 40-50%.12
Complementary and Integrative Therapies
Individuals suffering from migraine often seek complementary and integrative health (CIH) therapies to treat their symptoms.13,14 According to the National Health and Nutrition Examination Survey (NHANES), 18.7% of adults completing the survey reported suffering from headache and migraine; 37.6% of adults suffering from headache and migraine reported CIH use, and use increased with increasing severity of headache and migraine.15 The most popular reported CIH therapies included manipulative therapy, herbal supplementation, and mind-body therapy.15 Other studies have estimated that 28-82% of headache patients report CIH use.16 Unfortunately, not all CIH therapies that patients use to treat migraine are supported by evidence. However, acupuncture and neuromodulation are two non-pharmacological treatment options that are supported by evidence in treating migraine in adults.6,12
Acupuncture is a traditional Chinese medicine (TCM) practice that treats conditions by inserting thin needles into specific points called acupoints.14 In both China and the United States, acupuncture is used acutely to treat migraine pain and to prevent future migraine attacks.14,17,18 Acupoints are chosen by several different methods, which include eliciting tenderness at common local points while other points are chosen based on TCM principles of energy redistribution for symptom-
specific conditions.14 Once inserted into the acupoint, the acupuncture needles may be stimulated by the acupuncturist moving the needle slightly or by electrical stimulation, which is called electroacupuncture.14,17 A common local acupoint used in the treatment of migraine is Tai Yang EX-HN-5 in the temporal area; GV-20, GB-14, and Yin Tang are commonly used regional points.14
Mechanism of Action
The mechanism of action of acupuncture and its effects on migraine are not fully understood.12,17 One hypothesis is that acupuncture may activate the endogenous antinociceptive system, which would modulate pain response and transmission.17 Acupuncture has been shown to reduce sympathetic nerve activity and to dilate cerebral vascular vessels.19 In a migraine rat model study, acupuncture reduced levels of nitric oxide, which may be another potential mechanism of action in migraine.20 Acupuncture also has been shown to reduce plasma levels of CGRP, which is partially responsible for the neurogenic inflammation in a rat model.21 Further complicating the understanding of the mechanism of action and effectiveness of acupuncture is the placebo effect that occurs in the research comparison group of which sham acupuncture often is included.
Previous studies investigating the efficacy of true, or verum, acupuncture as a treatment for migraine prevention have been complicated by the placebo-like effects of sham acupuncture. Sham acupuncture techniques include not inserting the needles into the acupoint fully and/or using other non-acupoints to place needles.13,18,19,22 In a study comparing the effectiveness of placebo treatments in migraine prophylaxis, sham acupuncture (proportion of responders, 0.38; 95% confidence interval [CI], 0.30-0.47) and sham surgery (0.58; 95% CI, 0.37-0.77) were found to be associated with a more pronounced reduction in migraine frequency than oral pharmacological placebos (0.22; 95% CI, 0.17-0.28).22 Sham acupuncture groups have been found to report an increased placebo response compared to oral pharmacological placebo groups (odds ratio, 1.88; 95% CI, 1.30-2.72).22
A Cochrane Review published in 2016 investigating the efficacy of acupuncture as a treatment in the prevention of episodic migraine found acupuncture to be beneficial.13 There was a moderate reduction of headache frequency compared to no acupuncture (four trials, 2,199 participants; standardized mean difference [SMD], -0.56; 95% CI, -0.65 to -0.48); findings also were statistically heterogeneous (I2 = 57%; moderate quality evidence). Forty-one percent of participants receiving acupuncture had a headache frequency that was at least halved compared to 17% receiving no acupuncture (relative risk [RR], 2.40; 95% CI, 2.08-2.76; four studies and 2,519 participants; number needed to treat for an additional beneficial outcome [NNTB], 4; 95% CI, 3-6; I2 = 7%; moderate quality evidence). Only one study in the analysis included post-treatment follow up at 12 months after randomization and found a small but significant benefit (RR, 2.16; 95% CI, 1.35-3.45; NNT, 7; 95% CI, 4-25; 377 participants, low-quality evidence). Acupuncture reduced the frequency of migraines significantly more than drug prophylaxis after treatment (SMD, -0.25; 95% CI, -0.39 to -0.10; three trials, 739 participants). However, at follow-up, no significant difference was found. Fifty-seven percent of participants receiving acupuncture and 46% receiving prophylactic drugs had a headache frequency that was halved at three months (pooled RR, 1.24; 95% CI, 1.08-1.44). Participants receiving acupuncture were less likely to experience adverse effects and drop out (OR, 0.27; 95% CI, 0.08-0.86; four trials, 451 participants) than participants receiving prophylactic drugs (moderate quality evidence). The authors concluded that a course of acupuncture for at least six treatment sessions may benefit patients with migraine. The authors further calculated that if a patient has an average of six days with migraine per month before starting acupuncture treatment, it would be reduced to three and a half days with true acupuncture.13
In a recent randomized, controlled trial in China investigating the long-term effect of prophylactic acupuncture for migraine without aura, true electroacupuncture significantly reduced the frequency of attacks at 16 weeks compared to both the sham acupuncture and waitlist groups.19 This study included 249 participants between 18 and 65 years of age who suffered from migraine without aura occurring two to eight times per month. Both the verum acupuncture and sham acupuncture groups received treatments five days per week for the first four weeks and then were followed for a total of 24 weeks. At 16 weeks, there was a significant difference (P = 0.001) in migraine frequency measured between the three groups, with the verum acupuncture group demonstrating a mean (SD) of 3.2 attacks (2.1), sham acupuncture group 2.1 attacks (2.5), and the wait list group 1.4 attacks (2.5). The verum acupuncture group had a significant decrease in frequency compared to the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = 0.002) and the wait list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P < 0.001).19
Auricular, or ear, acupuncture also has been found to be beneficial in the reduction of pain in migraine without aura attacks.15 In a randomized, controlled trial with 35 participants with migraine without aura, researchers compared traditional acupuncture with ear acupuncture and found a reduction in migraine severity after eight weeks of weekly treatments. Both groups had improvements from baseline and both groups were comparable at the end of treatment and three months later. After six months, residual pain was 16.80% and 48.83% for somatic and ear acupuncture, respectively (P = 0.038).15
Acupuncture generally is safe; however, mild adverse effects, such as tingling, mild swelling, and occasionally subcutaneous hemorrhage at needle insertion sight, have been reported.19
Peripheral neuromodulation is a treatment that delivers electrical stimulation to targeted sites and alters the nerve activity. It can be either invasive (occipital nerve stimulation or stimulation to the sphenopalatine ganglion) or non-invasive (single pulse transcranial magnetic stimulation, transcutaneous vagal nerve stimulation, or transcutaneous supraorbital nerve stimulation).6 This review will focus on the noninvasive neuromodulation approaches.
Single pulse transcranial magnetic stimulation is a painless method that has been shown to be effective in treating migraine pain. The mechanism of action that is believed to be responsible for the decreased migraine pain is through blocking cortical spreading depression.6,23 In a randomized, double-blind, placebo-controlled, parallel-group study in patients with migraine with aura, a single pulse transcranial magnetic stimulation device (Cerena Transcranial Magnetic Stimulator [eNeura]) decreased migraine pain.6,23 The eNeura is used over the occipital cortex. This study included 164 participants who treated their migraine with aura after it started; there was a 39% reduction in pain in the active treatment group that was significantly different than the 22% reported by the sham group (P = 0.0179).6,23
Transcutaneous vagal nerve stimulation by the gammaCore device is approved for use in cluster headache; however, the evidence for use in treating migraine is still unclear. The device is applied to the neck and an adjustable electric current stimulates the cervical portion of the vagus nerve. The effectiveness of this treatment in migraine currently is being studied.6,23
Transcutaneous supraorbital nerve stimulation has demonstrated promise in treating migraine with the Cefaly device.8,23 A current of 16 mA is applied to the end branches of the trigeminal nerve and should be performed for 20 minutes each day to prophylactically treat migraine.8 There is some research to support its use, with 23 out of 35 (65.7%) participants expressing satisfaction with the device and showing a reduction of headache frequency at three months. Further studies are being performed to evaluate the efficacy of this treatment. Adverse effects, including paresthesias, have been reported.6,23,24
Transcutaneous occipital nerve stimulation (tONS) is a method of using transcutaneous electrical nerve stimulation (TENS) over the occipital nerves. The U.S. Food and Drug Administration has approved TENS stimulation over the supratrochlear and supraorbital nerve for the prevention of episodic migraine. In a prospective RCT investigating the effectiveness of tONS on migraine prevention, 110 participants were randomized to one of three tONS groups with differing frequencies delivered: Group A (2 Hz), Group B (100 Hz), and Group C (2/100 Hz).25 The tONS groups applied the electrode over the bilateral occipital nerves and received the electrical stimulation, while a sham control group did not receive the electrical stimulation. There was also a control group that did not receive tONS therapy but did take the migraine prevention medication topiramate (100 mg/day). At four weeks, the 50% responder rates of the tONS groups (36.36%, 40.91%, 36.36%) and the topiramate group (63.64%) were significantly different compared to the sham group (4.55%). There were no differences between the tONS groups and no difference in between the tONS group and the sham group. Decreased headache frequency was found in the 100 Hz tONS group and the topiramate group (P = 0.003 and P < 0.001, respectively). The tONS and TPM groups were equivalent in decreasing headache frequency. Adverse events were reported at the upper end of stimulation tolerability, with participants reporting a vibration sense that was considered normal. However, one patient in the 2 Hz group reported a “pinch” pain that went away when the intensity was reduced. Nine out of the 22 patients in the topiramate group reported adverse effects of hand and foot paresthesia.25
Many migraine patients are interested in non-pharmacological treatment options. Neuromodulation therapies demonstrate promise in treating patients with migraine. There are a number of studies underway investigating the efficacy of newer noninvasive neuromodulation devices.
Neuromodulation likely will continue to grow as a migraine treatment strategy, particularly with the newer noninvasive devices coming to market. More robust research is needed to understand both the efficacy and safety of these devices. The neuromodulation devices may be cost prohibitive for many patients, and insurance has yet to cover the devices.26 The Cefaly device is approximately $400, and if patients are not happy with it they can return it within the 60-day guarantee period.26 However, headache frequency was decreased at three months in the study, so recommending a 90-day trial is warranted.26 The Cefaly device tolerability is variable, so some patients are unable to tolerate the lower intensity setting.26 The eNeura device is available for rent for $150-250 per month and has demonstrated reduction in headache frequency in some patients.26 Recommending a trial of a neuromodulation device or referral to a specialist who recommends devices may be a great treatment option for patients who do not respond to medication for either lack of efficacy or increased side effects. More research needs to be conducted on the use of neuromodulation treatments to further elucidate mechanism of action and treatment protocols.
Acupuncture has been found to reduce migraine frequency, number of days with migraine, and pain intensity compared to the sham acupuncture and wait list groups. It is reasonable to recommend a trial of acupuncture for at least six visits and then follow up with the patient to evaluate treatment efficacy. For patients who are uneasy with needles or short on time, recommending auricular acupuncture may be beneficial in the treatment of migraine. Electroacupuncture, which uses a TENS unit that is connected to the inserted needles stimulating the acupoints, is a reasonable recommendation to patients. Acupuncture treatments can be cost-prohibitive for patients, as insurance does not always cover treatments and there is a wide range of treatment cost. When recommending acupuncture, providers should recommend that patients try acupuncture for six visits and then follow up to reevaluate the effectiveness of the intervention.
- Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the United States: Disability and economic costs. Arch Intern Med 1999;159:813-818.
- Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: Data from the American Migraine Study II. Headache 2001;41:646-657.
- Global Burden of Disease 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the Global Burden of disease study 2013. Lancet 2015;386:743-800.
- Puledda F, Messina R, Goadsby PJ. An update on migraine: Current understanding and future directions. J Neurol 2017; Mar 20. doi: 10.1007/s00415-017-8434-y. [Epub ahead of print].
- Lafreniere RG, Cader MZ, Poulin JF, et al. A dominant-negative mutation in the TrESK potassium channel is linked to familial migraine with aura. Nat Med 2010;16:1157-1160.
- Diener HC, Charles A, Goadsby PJ, Holle D. New therapeutic approaches for the prevention and treatment of migraine. Lancet Neurol 2015;14:1010-1022.
- Merikangas KR, Risch NJ, Merikangas JR, et al. Migraine and depression: Association and familial transmission. J Psyciatr Res 1988;22:119-129.
- Honkasalo ML, Kaprio J, Winter T, et al. Migraine and concomitant symptoms among 8167 adult twin pairs. Headache 1995;35:70-78.
- Malhotra R. Understanding migraine: Potential role of neurogenic inflammation. Ann Indian Acad Neurol 2016;19:175-182.
- Leao AA. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944;7:359.
- Berger A, Bloudek LM, Varon SF, Oster G. Adherence with migraine prophylaxis in clinical practice. Pain Pract 2012;12:541-549.
- International Classification of Headache Disorders. Available at: . Accessed Aug. 10, 2017.
- Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev 2016;(6):CD001218.
- Wells RE, Baute V, Wahbeh H. Complementary and integrative medicine for neurologic conditions. Med Clin N Am 2017;101:881-893.
- Millstine D, Chen CY, Bauer B. Complementary and integrative medicine in the management of headache. BMJ 2017;357:j1805.
- Zhang Y, Dennis JA, Leach MJ, et al. Complementary and alternative medicine use among US adults with headache or migraine: Results from the 2012 National Health Interview Survey. Headache 2017;57:1228-1242.
- Adams J, Barberry G, Lui CW. Complementary and alternative medicine use for headache and migraine: A critical review of the literature. Headache 2013;53:459-473.
- Wu GC. Acupuncture analgesia in migraine. Chinese J Integr Med 2009;14:248-250.
- Zhao L, Chen J, Li Y, et al. The long-term effect of acupuncture for migraine prophylaxis: A randomized clinical trial. JAMA Intern Med 2017;177:508-515.
- Backer M, Grossman P, Schneider J, et al. Acupuncture in migraine: Investigation of autonomic effects. Clin J Pain 2008;24:106-115.
- Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008;85:355-375.
- Meissner KK. Differential effectiveness of placebo treatments: A systematic review of migraine prophylaxis. JAMA Intern Med 2013;173:1941-1951.
- Puledda F, Goadsby PJ. An update on non-pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache 2017;57:685-691.
- Robbins M, Lipton R. Transcutaneous and percutaneous neurostimulation for headache disorders. Headache 2017;57:4-13.
- Liu Y, Dong Z, Wang R, et al. Migraine prevention using different frequencies of transcutaneous occipital nerve stimulation: A randomized controlled trial. J Pain 2017;18:1006-1015.
- Tepper S. Non-invasive neuromodulation: The next step in migraine care. Pract Neurology 2017;30-33.