Neuromodulation: History and Updates


Neuromodulation represents an advanced pain management therapy for patients with chronic, refractory pain.


Neuromodulation represents an advanced pain management therapy for patients with chronic, refractory pain. The term “neuromodulation” refers to the therapeutic administration of electrical stimulation (or chemical agents) directly to the nervous system (spinal cord, brain or peripheral nerves) in order to modulate nerve cell activity. The aim is to interrupt pain signalling at the point of stimulation, thus stopping pain signals from reaching the brain.

History of Neuromodulation

The first sophisticated application of neuromodulation dates back to the early 1960’s, when deep brain stimulation (DBS) was first used to treat chronic, intractable pain. DBS involves the surgical implantation of electrodes within the brain that are wired to a pacemaker type device that is implanted under the skin on the chest. The device delivers electrical impulses to the target brain areas in order to mask abnormal activity. In the present day, DBS is primarily used in the treatment of neurological movement disorders, such as Parkinson’s disease, essential tremor and dystonia.

The application of spinal cord stimulation (SCS) commenced shortly after DBS, in 1967, and it is now the most established neurostimulation modality for the treatment of chronic, refractory pain, with a well-documented efficacy and safety profile. Traditional SCS produces tingling or “pins and needles” sensations, known as paraesthesia, to mask the pain.

Spinal Cord Stimulation

Indications for SCS

The two most common indications for SCS are failed back surgery syndrome (ongoing pain post back surgery) and complex regional pain syndrome (CRPS). The effectiveness of SCS is most well demonstrated in lower back and leg pain, although advancements in the technology are providing effective pain relief in a wider range of pain distributions.

What is Involved?

SCS involves the implantation of leads into the epidural space that are connected to an implanted pulse generator (IPG), which is generally placed under the skin on the lower backside. The position of the stimulating leads along the spinal cord depends on the area of pain. For SCS systems that mask the pain by producing paraesthesia, the implanting physician will conduct “paraesthesia-mapping”. This requires the patient to communicate with the physician during lead placement in order to locate the position along the spinal cord which best provides coverage of their area of pain.

Before permanent implantation of the device, patients undergo a trial. Trial leads are implanted and connected to an external device. The trial usually lasts about a week, during which the patient completes a daily assessment of the SCS therapy. The trial is successful if the patient experiences a ≥50% decrease in pain, or significantly benefits in terms of disability and/or functionality. Many SCS patients are also able to reduce their analgesic medication intake.

Patients will need to attend a series of programming sessions with a technician from the SCS device company. During these sessions, stimulation parameters are tweaked and different stimulation programs are set for the patient to test or switch between if necessary. With regular programming, the relief gained from SCS can be optimised to suit the individual’s needs.

Updates in SCS Therapy

Many patients will achieve significant benefits from traditional SCS systems. For patients who do not respond to traditional SCS, have a more complex pain distribution, or find paraesthesia uncomfortable, pain relief may be achieved with alternative, more recently developed SCS technologies.

High Frequency SCS

High frequency SCS systems deliver significantly higher electrical stimulation - up to 10 kHz, compared to traditional stimulation which is delivered at around 50 Hz. This therapy does not produce paraesthesia, which is great for patients who find paraesthesia uncomfortable. Furthermore, the process of paraesthesia-mapping is not required during surgery, meaning shorter operating times. Both high frequency and traditional SCS are effective for leg pain, however, studies have shown high frequency SCS to be more effective in a greater percentage of patients with predominant back pain.

Burst SCS

In these systems, high frequency stimulation is delivered in closely-spaced “bursts”, as opposed to traditional SCS in which electrical stimulation is delivered at a consistent, low frequency (“tonic” stimulation). This mode of SCS is also paraesthesia-free.

Dorsal Root Ganglion Stimulation

Dorsal root ganglia (DRG) are bundles of sensory nerve cell bodies that are located at the rear of the spinal vertebrae, next to the dorsal nerve roots which emerge from the spine. DRG regulate the entry of sensory information from the peripheral nervous system to the central nervous system. By targeting the DRG, pain signals originating from the limbs are interrupted before they enter the spinal cord. Some studies suggest that this therapy is more effective for CRPS than traditional SCS systems.

Closed-Loop SCS Systems

Conventional SCS systems are pre-programmed to deliver a fixed level of stimulation. This is known as an open-loop system. In order to optimise the therapy in an open-loop system, the stimulation settings are manually adjusted by the device technician during programming sessions; Patients may be given a single fixed stimulation program, or several fixed stimulation programs which they may switch between depending on their needs and stimulation sensation. More recently, closed-loop SCS systems have been trialed. A closed-loop system is an adaptive system, meaning that the level of stimulation is automatically adjusted depending on nerve activity, body position etc. With a closed-loop SCS system, uncomfortable stimulation sensations (i.e. due to changes in body position) may be avoided, while the effectiveness of the therapy is maintained.

Wireless SCS Systems

These are miniaturised SCS systems that do not contain an IPG. Instead, the small implanted system consists of electrodes with a built-in receiver. The implantable device may be inserted into the spine, at the DRG or along a peripheral nerve via needle. The implant procedure is minimally invasive and can be performed without sedation. The battery and transmitter are contained in an external, wearable device. The implanted system is activated (pulse generated) when the external device is placed on the skin within a certain distance of the internal receiver. This system can be used as often as needed, as long as the external device is worn. This is in contrast to fully implantable systems, which may be constantly switched on and regularly charged via a remote device.

Other Forms of Neuromodulation

Peripheral Nerve Stimulation

Nerves outside of the spinal cord can also be stimulated in order to treat chronic, refractory pain of the limbs. This is known as peripheral nerve stimulation (PNS). PNS is also used to treat conditions such as paraplegia and epilepsy. The target nerve is directly stimulated by implanting and anchoring an electrode on, near or around the nerve. Or, in the case of peripheral nerve field stimulation (PNFS), electrodes are placed under the skin within the site of most pain to stimulate the surrounding nerves.

Occipital Nerve Stimulation

Occipital nerve stimulation (ONS) is a form of PNS that specifically targets the occipital nerves, which run from the vertebrate in the neck to the scalp. ONS is an advanced therapy option for patients with chronic pain conditions of the head or neck that don’t respond to conventional treatments, such as chronic migraine, other headache syndromes and craniofacial pain.

Sacral Nerve Stimulation

The sacral nerves emerge from the lower part of the spine and forms a network known as the sacral plexus, which supplies motor and sensory nerves to the lower limbs, buttocks and pelvis. Sacral nerve stimulation (SNS) targets this plexus and may be used to treat chronic refractory pelvic pain, along with various other conditions such as bladder pain syndrome and even incontinence.

Clinical Trials

Genesis Research Services conducts clinical trials for numerous neuromodulation devices for various chronic pain conditions. If you would like to be informed about upcoming neuromodulation clinical trials, click here to view the currently enrolling trials or register your interest for future studies.


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