Right now, signals from your brain are instructing the muscles around each eye to contract, panning your view left to right and adjusting focus along the way. The photoreceptors in your eyes react to the photons reflecting off each letter, ultimately transmitting information through the optic nerve, back to the primary visual cortex, where they are translated into meaning. Although it goes mostly unnoticed, your nervous system is constantly hard at work.

Fig. 1 – Implanted devices, such as spinal cord stimulators for intractable pain, provide constant therapy for otherwise chronic conditions. However, the invasive nature of these devices limits the cases in which they are used.
In their simplest form, every function of the human body can be reduced to a series of electrochemical reactions in the nervous system. Whether you are reading this page, lifting your cup of coffee, feeling that you ate too much for breakfast, or recognizing the song playing on the radio, all can be traced back to the amazing, complex network of electrical connections and chemical reactions that is the human nervous system. The sensations we feel every day and how our body reacts to them are the result of thousands of receptors talking to each other. And now, scientists are getting in on the conversation.

Neuromodulation (or neurostimulation) is the application of electrical signals to promote, inhibit, or otherwise change neural behavior. Alan Lloyd Hodgkin and Andrew Huxley famously showed how nerves communicate through electrical impulses known as action potentials in 1952 (and won the Nobel Prize for their work a decade later). When a substantial electric potential builds up around a nerve, the nerve produces an impulse that travels to the end of the nerve cell body, where it connects with another cell via an electrical or chemical synapse. The action potential from one nerve can induce a similar potential in another nerve, allowing communication between cells. Sometimes this connection tells a muscle to contract. Other times, it relays sensory information back to the brain. However, these nerves can’t distinguish between an electrical signal from their neighbor and an electrical signal from an implanted electrode. These artificial signals provide an interface to communicate with the nervous system. As we learn more and more about the way nerves communicate and the pathways they exhibit, we can tailor our electrical impulses to speak the body’s natural language.

Electricity has actually been applied therapeutically for centuries, but not nearly as elegantly as implied above. In fact, the perception most have of electrotherapy is likely electroshock or electroconvulsive therapy, where electricity is broadly administered to the brain to treat psychiatric disorders. The kind of modulation detailed in this article is a very precise and targeted application, and unlike pharmaceuticals, it works with how the body functions naturally.

Fig. 2 – Percutaneous nerve stimulation delivers a small electrical current through a needle electrode that punctures the skin and is placed near the nerve of interest.
Traditional pharmaceuticals work by binding to molecules and disrupting the natural responses of the body. For example, aspirin produces an analgesic effect by inhibiting a specific enzyme in the inflammatory pathway. Without this enzyme, the body cannot release the molecules needed to signal pain and an inflammatory response. Pharmaceuticals are remarkable at treating the condition for which they are indicated. However, most of these drugs are administered system-wide, either orally or intravenously, and end up circulating through the bloodstream. What happens when the molecule itself causes unwanted side effects? Or achieving the desired effect in one location leads to an undesired effect in another (think blood thinners and internal bleeding)? Patients (and physicians) often assume pharmaceuticals to be the best treatment because they are a product of years of research at billion-dollar companies, but the list of side effects in any pharmaceutical commercial takes up half of the ad time.

Neuromodulation offers a level of specificity and sensitivity that pharmaceuticals can’t match. Rather than engineering a foreign molecule aimed at disrupting the natural processes of the body, it uses a language the body readily understands to provide a safe and effective therapy for all users.

Neuromodulation and Neurostimulation in Practice

Just as the nervous system uses these electrical signals to control every bodily function, scientists have tapped into these pathways to treat a wide variety of conditions. Though neuromodulation provides opportunities to tackle an endless number of conditions, we will focus on stimulation using electricity. Using the interplay between electricity and magnetism, many companies are using the latter as a modality for therapy. The underlying concept of producing an electrical field remains the same, but is beyond the scope of this piece.

In cases of intractable, neuropathic pain, spinal cord stimulators have proven to be successful in treating symptoms that are resistant to even the strongest pharmaceuticals. The device consists of a small electrical generator positioned in the lower back and a collection of leads that hardwire the electrode directly to the nervous tissue in the spine. The device delivers small electrical currents that provide relief by blocking transmission of pain signals from the extremities up to the brain.

Fig. 3 – Transcutaneous (or transdermal) stimulators, like the Neurowave product family, use tissue as a conductive pathway between the electrode and the nerve. Though the current is attenuated, superficial nerves can be stimulated without skin irritation.
Instead of inhibiting neural activity, functional electrical stimulation (or FES) systems apply electricity to stimulate the motor neurons of muscles that are impaired by lesions in the central nervous system. These are muscles that are otherwise paralyzed by stroke, spinal cord injury, or traumatic brain injury. Even though the neural connection to these muscles has been disrupted, they remain healthy for some time after injury and can be stimulated artificially. FES has been used to allow individuals with paraplegia to stand and even walk when given appropriate upper body support. When the lesion is present higher in the spinal cord, even vital organ function can be disrupted. In these cases, FES has restored bladder and bowel control and phrenic nerve stimulation can control respiration.

Another type of functional stimulation, and arguably the best known, is the artificial pacemaker. Although the human heart has an independent “nervous system” in the form of pacemaker cells, their function can be modulated in the same way. Small, precisely timed electrical currents contract the muscles of the heart, ensuring continuous blood flow in the face of cardiac failure, asynchronous contraction, and arrhythmia. The same concept is being applied to other rhythmic bodily functions, such as pacing stomach contractions for patients with gastroparesis or delayed stomach emptying.

At the forefront of modern research, deep brain stimulation (DBS) bypasses the periphery of the nervous system and directly stimulates specific locations of the brain. Probably best known for suppressing essential tremor and the movement disorders associated with Parkinson’s disease, DBS has also shown to be remarkably effective in treating major depression, epilepsy, and some forms of Tourette’s syndrome. Current research is investigating DBS as a treatment for Alzheimer’s and even obesity.

As successful as these therapies have proven, the design and implementation of the devices has consistently been an obstacle to market penetration. Traditional transcutaneous electrical nerve stimulation (TENS) units can only be worn for short periods of time as a phenomenon called short-term habituation causes nerves to be less sensitive to repeated stimuli. This is why after a few minutes of having your hand in ice, the cold does not feel as severe. For TENS, this requires increasing stimulation in tensity to get a comparable effect. Excess application of electrical energy will ultimately cause skin irritation and patient discomfort.

Fig. 4 – Neurowave Medical Technologies offers transdermal neuromodulation devices cleared by the FDA to treat multiple indications of nausea and vomiting, including post-operative nausea and vomiting, chemotherapy-induced nausea and vomiting, and pregnancy-induced nausea and vomiting (morning sickness). The PrimaBella is the only product (drug or device) cleared by the FDA to relieve morning sickness.
The drawbacks of an implanted system are more dramatic. Placement of any gastric or cardiac pacemaker, bowel or sacral nerve stimulator (for incontinence) requires an invasive surgery. Ensuring the proper placement of a spinal cord stimulator requires a patient to undergo a preliminary surgery in which electrical leads are implanted in the spine and connected to a temporary external device. Once the therapeutic effect is confirmed, a second surgery places the permanent device. Even then, studies show upwards of 40% of SCS implants require surgical revision. Post-operative maintenance of an implant can require wireless recharging of the implant on a weekly basis and/or having the system replaced after a decade because the primary cell battery has failed. As is the case with most metal implants, neurostimulators usually prevent the use of magnetic resonance imaging (MRI).

Deep brain stimulators must eventually overcome the consequences of directly stimulating the brain. Like any other neuromodulation technique, DBS offers specificity to the location being targeted. However, our understanding of all the connections in the brain and central nervous system is far from complete. Scientists may be able to associate a condition with a specific location, but the complexity of the brain likely implicates that location with countless other bodily functions.

Tackling Design Challenges in Neuromodulation

To summarize the first two sections is to summarize the problems faced by medical device designers looking to move into this field. Neuromodulation offers remarkably safe and efficacious treatment for countless conditions, though the current embodiments of these therapies limit their mass adoption. Fortunately, the continuous advancements in electrical and mechanical engineering, as well as an improved understanding of neural function, are making neurostimulation a more attractive therapy.

These design improvements can be characterized into many categories, though they are all connected by the common goal of providing the best treatment for the patient.

Improving Patient Compliance

With most medical devices, the efficacy of treatment drops considerably when patients are required to participate actively in their maintenance. We’ve all forgotten to charge our cell phones before we’ve gone to bed. What if instead of your phone, that is your spinal cord stimulator and without it, the pain in your lower back is so bad you can barely walk? For better or for worse, medical devices are designed to be discreet and easily hidden and, especially in the case of an implant, often not something patients interface with on a daily basis.

Although the minimally invasive treatments have obvious benefits over their implanted counterparts, they require patients to take an even more active role. Percutaneous stimulation treatments require visits to the physician or specialist for proper placement of needle electrodes. Once in place, the patient is confined to a chair for the duration of the treatment. The case is similar in rechargeable implant devices because current recharging systems are so sensitive to misalignment.

From a patient standpoint, innovation will reduce the work needed to receive therapy. Higher energy density batteries can reduce the need for recharging on a weekly basis. Even with current charging systems, improvements in interface design would allow users to stay on top of their maintenance. Though implanted devices remain unseen, they already have onboard telemetry systems that could alert patients of low battery level through their phones.

Improving Patient Comfort

In the past decade, we’ve already seen the size of implantable stimulators cut in half. Not only does this decrease the profile of superficial implants, but it also allows for alternative implant locations much closer to the stimulation site. As electrical components shrink in size, the potential to shrink the size of implants increases. One of the largest contributors to the bulky implant design is the primary or secondary cell battery, furthering the need for improved battery technology.

Or what if there wasn’t a battery in the first place? The advent of safe wireless power could remove the battery and eliminate the need for invasive surgery altogether. A wireless system also addresses the system failures due to electrodes moving from their implant site by reducing stress on the electrical leads, providing a more reliable device and a very attractive therapy.

Even without wireless power, implanted devices are moving outside of the body. Percutaneous and transcutaneous devices stimulate the same nerves, only using needle or surface electrodes. Unique waveforms and electrode designs allow for comfortable stimulation of the same nerves once met only with implants. As our understanding of the nervous system grows, novel targets for stimulation are identified, often superficial nerves, to provide new drug-free treatments.

Neuromodulation in Today’s Market

Neurowave Medical Technologies (NMT) (Chicago, IL) focuses on modulating neural function through innovative transdermal electrical modulation devices. NMT currently offers solutions for a variety of nausea and vomiting indications. All are drug-free and available by prescription. They include Reletex™ (for post-operative nausea and vomiting), Nometex™ (for chemotherapy-induced nausea and vomiting), and PrimaBella™ (for morning sickness). Currently, the PrimaBella™ is the only product (device, drug, or otherwise) cleared by the FDA for the treatment of morning sickness.

Neuromodulators from NMT are worn on the underside of the wrist, where they use patented and proprietary technologies to stimulate the median nerve. Stimulation at this point modulates activity in the emetic center of the brain and regulates the abnormal stomach rhythms associated with nausea and vomiting. The small, lightweight device provides portable, fast-acting relief, and the stimulation is designed to avoid the nerve fatigue and habituation often associated with transdermal stimulation.

Products like the Neurowave Medical family of transcutaneous nerve stimulators are helping transform the image of neuromodulation from the electroshock chambers of a psychiatric ward to a safe and effective treatment for a multitude of conditions. As technology and our understanding of the nervous system simultaneously improve, neuromodulation is moving from a last line of defense to a front-line therapy.

This article was written by Matthew Geary, Manager of New Product and Technology Development for Neurowave Medical Technologies in Chicago, IL. Contact Matthew at This email address is being protected from spambots. You need JavaScript enabled to view it., or visit http://info.hotims.com/40429-162 .