Advances in Neuromodulation: Spinal Cord Stimulation

As discussed in the last Dr. Gearhead column (ASA Monitor 2024;88:1,6), neuromodulation can be achieved through either chemical or electrical stimulation. The advancement and application of neuromodulation has transformed the landscape for chronic pain patients suffering from intractable pain conditions. The application of electrical stimulation to peripheral nerve targets is achieved through peripheral nerve stimulators (PNS), and the application of electrical stimulation at the level of the spinal cord is achieved through dorsal column or spinal cord stimulators (SCS), with an additional option for stimulation at the level of the dorsal root ganglion (DRG). For this article, we will discuss the advancements in the field of traditional spinal cord stimulation that have helped improve the efficacy of the therapy provided and pushed the scope of application for myriad pain conditions.

Traditional SCS systems, initially introduced in 1960s, involved delivery of electrical impulses to the dorsal horn of the spinal cord to modulate signals travelling to the brain (Pain Medicine 2006;7:S7-13). The first proposed mechanism to explain the mechanism of SCS was based on the gate control theory by Melzack and Wall, with modulation of the pain impulses at the level of the spinal cord before they reach higher centers. Further research showed that there are other spinal and supraspinal mechanisms also at play, with continuing work in the field due to an incomplete understanding of the mechanisms (Bioelectron Med 2019;28:12). The SCS system as we know it today consists of four components that work together – leads, implantable pulse generator (IPG), battery recharger (if a rechargeable battery is used), and programmer. Typically, two leads are placed in the dorsal epidural space surrounding the spinal cord at the midline target level known to modulate corresponding pain complaints. The leads are connected to the IPG, directly or through extension wires, which is placed under the skin, usually below the belt line in the lateral buttock region. The IPG is programmed to send impulses to the lead contacts, and an external handheld programmer can be used by the patient to turn the stimulation up, down, or off, or to change programs.

In 1968, the first SCS was implanted in humans by a neurosurgeon, Dr. C. Norman Shealy. Initial systems involved surgical implantation of a subdural electrode, through a laminectomy (Bioengineering 2023;10:185). This involved increased risk of cerebral spinal fluid (CSF) leak or spinal cord injury. Subsequently, the pioneering of percutaneous electrodes placed epidurally through hollow needles obviated the need for a laminectomy and reduced the risk of a CSF leak. The percutaneous method is the most common practice of SCS leads insertion today. Open surgical placement of leads is reserved for patients with technical or anatomical challenges. The early days of percutaneous SCS systems suffered from therapy failure due to frequent lead migration. To overcome this effect, the number of stimulating contacts each on the cylindrical lead was increased from four to eight, and subsequently, 16. In addition to further mitigating lead migration, mechanical anchors became available that prevented lead slippage through the anchor. Having multiple leads allows the flexibility to reprogram the electrodes in case of small migration of leads (Neurosurgery 1993;32:384-95).

The initial systems had an external pulse generator (EPG) that used radiofrequency waves for communication and power to generate electrical stimulation. With advancement of lithium-based batteries, the radiofrequency based bulky EPG systems were replaced by IPGs. This improvement in design led to widespread adoption of the therapy. Further advancement in IPG technology saw improvement in battery life that reduced the need for frequent surgical intervention to change the batteries. The average battery life for rechargeable batteries is about seven to 10 years, as compared to the nonrechargeable batteries that last on average two to five years. The reduction in size of the IPG has helped increase patient comfort without compromising the therapeutic benefit. The SCS systems that are in use currently have MRI compatibility, the lack of which had earlier prevented patients from undergoing implants or at times needing to have them removed.

Improvement in design and hardware for SCS corresponded with improvement in the software and programming. The IPG sends electrical signals to the leads through different waveforms. The SCS waveforms are characterized by the following parameters: Amplitude – strength of the pulse (set in milliamps, mA); Pulse width – how long each pulse is in microseconds, Frequency – the number of pulses per second (set in Hertz, Hz); and the pulse shape (Bioengineering 2023;10:185). The traditional SCS devices were set to deliver tonic stimulation, which is low frequency (40-80 Hz), higher amplitude (3.5-8.5 mA), and higher pulse width (200-500 μS). This usually produces tingling (also known as paresthesia) and results in higher amounts of charge delivered per pulse after placing electrodes in the epidural space at targeted spinal levels. Intraoperative mapping is utilized with tonic SCS to achieve paresthesia overlapping somatotopic pain complaints, which remains necessary in the vast majority of cases to achieve sufficient pain relief. Although conventional tonic SCS waveform has been around for several decades, there are subsets of patients who either did not appreciate pain relief, failed to tolerate the sensation of paresthesia, experienced very positional stimulation, reported poor paresthesia overlap with pain complaints, or had reduced effectiveness over time. The shortcomings of paresthesia-based SCS devices were the driving force for the discovery of other novel stimulation strategies.

Increased knowledge in the field led to the introduction of new waveforms known as burst, high-frequency and differential target multiplex (DTM) waveform, and fast-acting subperception therapy (FAST) (Neurosurgery Clinics of North America 2022;33:287-97). These newer waveforms also are generally paresthesia-free. First, burst SCS was introduced, which involves delivery of high-frequency stimulation (five 1 millisecond pulses, at an inter-burst frequency of 500 Hz) in short bursts – about 40 bursts per second. This leads to differential modulation in the dorsal column and dorsal horn, in turn resulting in differential activation in the brain and also leading to modulation of lateral and affective pathways. Then came high-frequency SCS waveform that involves delivery of small electrical pulses at a very high frequency (10,000 Hz), resulting in paresthesia-free subthreshold stimulation. Given the lack of paresthesia with no need for intraoperative mapping, the leads for this system are placed in the anatomical midline. It has been postulated that high-frequency stimulation works through activation of inhibitory interneurons in dorsal horn while sparing activation of dorsal column fibers. DTM-SCS involves multiplexed signals with frequencies between 50-1,200 Hz and pulse widths between 50-400 μS to target different areas of spinal cord. DTM works through modulation of glial cell pathways, which play a central role in chronic neuropathic pain. The newest novel nonparesthetic stimulation is FAST, which depends on active recharging balance. After paresthesia mapping is optimized, the amplitude is reduced in a range of 30%-60% from sensory threshold with frequency set to 90 Hz and pulse width to 230-260 microseconds (Expert Rev Med Devices 2021;18:299-306). This allows for rapid onset of analgesic effect and works through surround inhibition at the spinal cord level to reduce wide dynamic range neuron firing.

Another advancement in the field of neurostimulation has been adaptive stimulation, also known as closed loop stimulation (asamonitor.pub/4dhOb1m). The conventional SCS systems have worked in an open loop manner – meaning with fixed parameters that can be adjusted manually, whereas the closed-loop SCS systems monitor the response to stimulation at the spinal cord level and make rapid adjustments to the stimulation as needed; for example, when changing body positions. The closed-loop systems are considered to be better at maintaining patients in the therapeutic window without over- or under-stimulating the spinal cord, resulting in improved pain relief.

Although there are increased programming capabilities, work is still being done to improve our understanding of the mechanisms of action and the clinical efficacy of the newer waveforms. Currently, there is no one single waveform for all pain conditions. Progress in the field has allowed for expansion of indications for SCS, from postlaminectomy syndrome and complex regional pain syndrome, to painful diabetic neuropathy and refractory nonsurgical low back pain.

The evolving landscape of spinal cord stimulators represents a significant leap forward in the field of pain management. As both research and technology continue to evolve, the future holds promise for even more innovative solutions that will revolutionize the way we approach electrical neuromodulation for chronic pain.