VOLUME 29, ISSUE 2

Jonathan Hagedorn, MD

Chief Anesthesiology Resident
Baylor College of Medicine

Spinal Cord Stimulation Overview and Review of Emerging Technology

Introduction

Since the introduction of neuromodulation for the treatment of chronic pain nearly 50 years ago, the field has rapidly progressed (1). This is particularly true over the past decade. In traditional spinal cord stimulation (SCS), the goal is to replace the area of pain with a paresthesia sensation. While this typically does lead to a reduction in pain scores, often times the paresthesias cause patient dissatisfaction and sleep disturbances. For this reason, SCS systems have been developed that reduce or avoid paresthesias while providing pain relief. This article provides an overview of SCS and a review of three emerging technologies.

Spinal Cord Stimulation Mechanism of Action

While there is still much to learn regarding the pain control mechanisms behind SCS, research has identified several possible etiologies. Originally known as “dorsal column stimulation”, SCS involves the placement of electrodes over the dorsal aspect of the spinal cord in the epidural space. The axons of the large diameter afferent sensory neurons are located in this location. According to the gate-control theory, stimulation of these axons in the dorsal column activates inhibitory interneurons which in turn attenuate spinal ascending pain transmission (2,3). Specifically, this involves the laminae II dorsal horn through gamma-aminobutyric acid (GABA) (4).

In addition to GABA, SCS analgesia likely involves the release of other neurotransmitters. Several studies have highlighted the importance of serotonin release and activation of serotonin receptors to SCS effectiveness (5,6). This decreases neuronal excitability and pain transmission. There have also been studies showing SCS release of acetylcholine and norepinephrine. Activation of spinal muscarinic receptors by acetylcholine has been shown to inhibit neuropathic hypersensitivity (7). Additionally, studies have shown excitatory muscarinic and alpha-1 receptors on the inhibitory GABAergic interneurons, thus acetylcholine and norepinephrine may contribute to attenuation of the spinal ascending tracts (8,9).

Traditional Spinal Cord Stimulation

Typically, electrodes are placed percutaneously into the epidural space and lay on the dorsal aspect of the spinal cord. Traditional devices can deliver pulse frequencies ranging from 2 – 1,200 Hz, but are commonly programmed at 40 – 60 Hz. Patients initially undergo a trial with an external power source before having an implantable device placed subcutaneously if the trial is successful. The implantable device produces tonic waveforms at a constant frequency, pulse width, and amplitude.

High Frequency Stimulation

High frequency stimulation (HF10) has been approved for use in Australia and Europe since 2011 and the United States since 2015. It involves the use of a subthreshold, low amplitude waveform at 10,000 Hz, thus providing pain relief while avoiding paresthesias.

The Senza study was a randomized controlled trial (RCT) comparing HF10 and traditional SCS. There was a total of 171 patients included in the data analysis with 90 in the HF10 group and 81 in the traditional SCS group. The first endpoint of the study was a greater than 50% reduction in back pain. In the HF10 group this was achieved in 80.9% and 78.7% of patients at three and twelve months, respectively. In comparison, the traditional SCS group showed an endpoint goal of 42.5% and 51.3% of patients at three and twelve months. The second endpoint of the study was a greater than 50% reduction in leg pain. In the HF10 group this was achieved in 83.1% and 78.7% of patients at three and twelve months. In the traditional SCS group the endpoint goal was achieved in 55.0% and 51.3% of patients at three and twelve months. These differences were all statistically significant, and showed superiority of HF10 versus traditional SCS for the treatment of back and leg pain (10).

The same group of patients was followed for 24 months with 156 patients available for data analysis with the same endpoints. At 24 months, more patients were responsive to HF10 than traditional SCS. For back pain, 76.5% of patients met the endpoint goal in the HF10 group versus 49.3% of patients in the traditional SCS group. For leg pain, 72.9% of patients met the endpoint goal in the HF10 group versus 49.3% of patients in the traditional SCS group. In terms of overall back pain decrease, HF10 provided a 66.9% decrease versus 41.1% in traditional SCS. The researchers concluded that HF10 showed long-term superiority to traditional SCS in treating both back and leg pain (11).

Burst Stimulation

Burst stimulation is a change in the mode of stimulation. Mode parameters involve an overall frequency of 40 Hz per burst complex. Each burst complex delivers 5 spikes 1 ms apart with a frequency of 500 Hz. This produces pain control with decreased or absent paresthesias. The pattern was developed because it mimics the natural firing of central nervous system neurons.

The Sunburst study is a prospective randomized trial comparing traditional and burst SCS. Patients are randomized on the order they will receive traditional or burst SCS. Stimulation modes are alternated at 12 weeks regardless of the initial mode. To date, the sample size is 85 patients. To be included, patients are required to have greater than 6/10 pain and a greater than 50% reduction in pain with a traditional SCS trial. Early data analysis shows that burst stimulation is statistically superior to traditional SCS with burst stimulation having an average decrease of 6 mm VAS. Of note, while this is statistically significant, it does not meet criteria for minimal clinically important difference (12).

Dorsal Root Ganglia Stimulation

Most recently, neuromodulation has focused on the dorsal root ganglion (DRG). The DRG is the location of the cell bodies for the primary sensory afferent neurons, thus becoming the site of transmission from peripheral to central nervous system. There is a single DRG between every spinal nerve and the spinal cord. This form of neuromodulation is a very specific and focused form of stimulation, which has been shown to be effective for failed back surgery syndrome and complex regional pain syndrome. By targeting specific DRG, treatment of focal areas of pain can be performed that may be difficult to target with traditional SCS.

The ACCURATE study was a RCT comparing DRG stimulation and traditional SCS. The study consisted of 152 patients, 76 randomized to the DRG group and 76 to the traditional SCS group. Each patient had pain for longer than six months with a visual analog scale greater than 6/10. The DRG group had superior results with 81.2% of patients having a greater than 50% reduction in pain at three months and 74.2% of patients maintaining that pain control at one year. In comparison, the traditional SCS group showed 55.7% of patients having a greater than 50% reduction in pain at three months and 53.0% of patients maintaining that pain control at one year. For the patients that went on to implant, the results were even better. At three months 93% of patients in the DRG group had greater than 50% reduction in pain and at one year 86% of patients maintained that level of pain control. In contrast, the traditional SCS showed 72% and 70% of patients at comparable time intervals (13).

Conclusion

Even though SCS was introduced decades ago, drastic technological changes have taken place in the past few years with the introduction of HF10, burst, and DRG stimulation. As we continue to grow our neuromodulation offerings, it’s likely that patient outcomes will continue to improve and approved indications will expand. ♦

References

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  2. Melzack R and Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971-979.
  3. Costigan M and Woolf CJ. No DREAM, No pain. Closing the spinal gate. Cell. 2002;108:297-300.
  4. Daniele CA and MacDermott AB. Low-threshold primary afferent drive onto GABAergic interneurons in the superficial dorsal horn of the mouse. J Neurosci. 2009, 29:686–695.
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  6. Song Z, Meyerson BA, and Linderoth B. Spinal 5-HT receptors that contribute to the pain-relieving effects of spinal cord stimulation in a rat model of neuropathy. Pain. 2011, 152:1666–1673.
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  8. Zhang HM, Chen SR, Cai YQ, Richardson TE, Driver LC, Lopez- Berestein G, and Pan HL. Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord. Neuroscience. 2009;158:1577–88.
  9. Chen SR and Pan HL. Spinal GABAB receptors mediate antinociceptive actions of cholinergic agents in normal and diabetic rats. Brain Res. 2003;965:67–74.
  10. Kapural L, Yu C, Doust MW, et al. Novel 10-kHz High-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA-RCT randomized controlled trial. Anesthesiology. 2015;123(4):851–860.
  11. Kapural L, Yu C, Doust MW, et al. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial. Neurosurgery. 2016;79(5):667-677.
  12. Deer T. Presentation. Paper presented at: 19th Annual North American Neuromodulation Society (NANS); 2015; Las Vegas, NV.
  13. Levy R. Presentation. Paper presented at: 19th Annual North American Neuromodulation Society (NANS); 2015; Las Vegas, NV.

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