The History of Neuromodulation as a Migraine Treatment  

The discovery of neuromodulation as a treatment for migraine was a fortuitous accident. Neuromodulation treats pain and other symptoms of migraine by stimulating or inhibiting neural activity, beneficially altering the way nerves carry information throughout the nervous system. 

The ancient roots of neuromodulation for migraine

The first known incident of primitive electrical neuromodulation predates modern devices by nearly 2,000 years, and began with a stroll on the beach by Anteros, a man enslaved by Roman emperor Caesar Augustus then freed. Instead of stepping on the sand beneath the surf, Anteros’ foot met the body of an electric torpedo ray fish. A shock from the animal left him breathless but mysteriously, the chronic pain Anteros experienced (from what may have been gout) disappeared.   

Word of Anteros’ healing reached Scribonius Largus, a court physician for the Roman Emperor Claudius. Anteros began experimenting with using the charges generated by torpedo fish placed against the forehead to treat chronic headache, and applied to the foot for gout pain. 

Other physicians across the ancient world began to use Largus’ techniques, but the mechanisms of action behind the treatment were unknown. “For thousands of years, people have been applying stimuli aimed at nerves that don’t ferry pain signals to affect the function of those that do, an effect known as neuromodulation,” writes Johns Hopkins Medicine about early forms of peripheral nerve stimulation to treat pain.  

It wasn’t until the 19th century that greater knowledge of electrical and mechanical principles led to the development of transcutaneous electrotherapy devices for a wide range of conditions, albeit with inconsistent results initially. 

The modern evolution of neuromodulation

The early to mid-20th century was the true dawn of neuromodulation as a pain treatment. The wider availability of batteries and later, greater understanding of the central nervous system’s role in pain led to portable and less invasive forms of neuromodulation.  

Early modern neuromodulation was first intended as a treatment for chronic pain, before later development of devices specified for migraine treatment.  

1950s-60s: The first neuromodulation devices

As early as the 1950s, scientists began experimenting with deep brain stimulation — stimulating targeted brain regions via electrical leads implanted in the brain — to control pain. DBS is the modern precursor to current, non-invasive modalities of neuromodulation. Today, DBS is primarily used as a treatment for movement disorders and neuropsychiatric conditions.  

In 1965, the Gate Control Theory of pain by Ronald Melzack and Patrick David Wall led to deeper understanding of the interconnectedness of nervous system functions, hastening the development of neuromodulation as a less invasive approach to treating chronic pain. Spinal cord stimulation emerged as another treatment for intractable pain.  

“As damage to the nervous system can itself cause chronic pain, there began a gradual move away from destructive surgical treatments such as cutting nerves and towards reversible, modulatory treatments: neuromodulation,” according to the International Neuromodulation Society. 

In 1967, neurosurgeon C. Norman Shealy was credited with developing the first implantable neuromodulation device, a spinal cord stimulator indicated for pain relief. Another group of physicians developed a less invasive spinal cord stimulator with reduced side effects by 1974. 

Concurrently, DBS technology continued to improve and by the 1970s, “there were reports of DBS systems implanted into the thalamus for chronic pain,” according to a review in the journal Neurotherapeutics.  

Late 1960s-1980s: Implantable peripheral neurostimulation  

Investigation of neuromodulation began to home in on the role of the trigeminal nerve in facial pain, moving closer to specifically treating headache. In 1966, neurologist C. Hunter Sheldon found that electrical stimulation of the trigeminal nerve was an effective treatment for trigeminal neuralgia, a form of chronic facial pain.  

In people with migraine, hypersensitive trigeminal nerve endings transmit distress signals to the brain in response to external triggers, which causes a cascade of neurological effects leading to migraine.  

Subsequent work by other researchers yielded positive findings on peripheral nerve stimulation as a treatment for neuropathic pain in the limbs. By 1976, the first clinical studies on the efficacy of peripheral nerve stimulation for pain management were published. 

In 1985, transcranial magnetic stimulation was invented by neurologist Anthony Barker. TMS utilizes magnetic field pulses to stimulate the prefrontal cortex through the scalp. Initially a treatment for epilepsy and later depression, TMS is currently also used to treat migraine.  

1999 to today: Migraine treatment with non-invasive neuromodulation devices

By the early 2000s, researchers began to recognize the potential of neuromodulation to specifically treat migraine. 

A 1999 report on the efficacy of electrically stimulating the occipital nerve to treat occipital neuralgia led to further research on treating head pain with neuromodulation.  “Subsequent investigators confirmed these initial findings, and then extended the application to patients with various primary headache disorders, including migraine,” according to a review published in Current Pain and Headache Reports.

In 2009, the supraorbital nerve was identified as an additional effective neuromodulation target for cluster headache. Combined supraorbital and occipital nerve stimulation was shown to be effective for the treatment of migraine.  

Today, researchers are digging deeper into the mechanisms behind what makes neuromodulation an effective treatment for migraine. In the 2010s, a series of small, hand-held transcutaneous neurostimulators targeting the trigeminal, occipital, and supraorbital nerves and other targets were FDA-cleared for at-home use.  

“The field of neuromodulation is fast shifting,” said Umer Najib, MD, FAHS, assistant professor in neurology at West Virginia University. “There are new devices that are being approved almost every year now. So, it’s good to keep up with the options; it’s good to know the indications of these devices and how to use them.” 

Today, a wide range of neuromodulation devices, leveraging multiple modalities, are used to safely and effectively treat migraine.