A Review of Neuromodulation Advancements
By Jonathan Hagedorn, MD
Chief Resident in Anesthesiology
Baylor College of Medicine
Spinal cord stimulation (SCS) for chronic pain was introduced in 1967 by Shealy. Since that time, and especially recently, the medical community has strived to improve SCS results through lower complication rates, expanded indications, technological compatibility, and innovative modalities. New technology has focused on updated programming, advanced waveforms, and specific localization of distinct stimulation targets. While traditional SCS (TSCS) relies on coverage of the painful area with paresthesias, recent advancements have allowed patients to live paresthesia-free and have improved pain control. This article will focus on the mechanisms of action and indications of high frequency (HF-10), dorsal root ganglion (DRG), and burst stimulation.
Traditional, low frequency 40-60 Hz SCS has been proven to be effective through multiple randomized controlled trials (RCT) for the indications of pain control in complex regional pain syndrome (CRPS), failed back surgery syndrome (FBSS), and painful peripheral neuropathy.[2-7] While the exact mechanism of action for SCS remains unknown, this form is proposed to work via activation of the A-beta fibers with electrical leads placed in the epidural space overlying the dorsal column of the spinal cord. When electrical stimulation is applied through these leads, a paresthesia can be produced in the painful dermatomal area. As explained by the gate control theory, this activation of large non-nociceptive A-beta fibers provides an inhibitory signal to the nociceptive A-delta and C-fibers in the dorsal horn of the spinal cord. Thus, masking the pain signal with the paresthesia signal. Other studies have noted SCS induced release of a variety of neurotransmitters as measured in the cerebrospinal fluid that may provide intracerebral effects as well.[8, 9] It is likely that the pain-relieving effects of SCS are multi-factorial and each SCS-induced change is important to its success.
While TSCS has proven beneficial for FBSS, HF-10 is the first major advancement that has shown greater improvement for this patient population. This unique waveform involves stimulation at 10,000 Hz applied at a subthreshold level. The exact mechanism of action of HF-10 remains unknown, but it’s hypothesized that the higher frequency provides a preferential block of large diameter fibers (A-beta, A-delta) compared to TSCS. In doing so, HF-10 inhibits the nociceptive A-delta signal along with the vibratory signal of the A-beta fibers. Another possible mechanism was described by McMahon and colleagues in 2017. Their work described a preferential stimulation of the dorsal column, which reduced the excitability of lamina I pain projection neurons involved in the spinothalamic tract. In 2015, Kapural et al. reported the results of an RCT comparing the efficacy of TSCS versus HF-10. One hundred seventy-one patients with both back and leg pain, of which approximately 80% were diagnosed with FBSS, were randomized to either TSCS or HF-10 and passed the trial for permanent implantation. At three months, 84.5% of HF-10 versus 43.8% of TSCS subjects were responders for back pain, and 83.1% of HF-10 versus 55.5% of TSCS for leg pain. At 24 months, more subjects responded to HF-10 than TSCS for back pain (76.5% versus 49.3%) and leg pain (72.9% versus 49.3%). Not only did more patients respond to HF-10, but the degree of improvement was also greater for HF-10 for both back and leg pain. These two RCTs provided strong evidence that HF-10 therapy is more beneficial than TSCS for patients having FBSS with leg pain.
The second major advancement is DRG stimulation, which was recently introduced as a novel stimulation location. The sensory afferents from the peripheral to the central nerve system must pass through the DRG. Inputs from different peripheral locations can be traced to specific DRG. Because of this, stimulation of the relevant DRG can modify the peripheral pain signals from specific areas of the body. In 2014, Liem et al. reported on 32 patients who were implanted with DRG stimulation for the indications of primarily FBSS and CRPS. At 12 months, overall pain improved by 56.3%, back pain by 41.9%, and leg pain by 62.4%. The percentage of subjects achieving at least 50% improvement of their overall pain was 60.0%, with 37.5% of back pain, 68.4% of leg pain, and 87.5% of foot pain responding. For back pain and leg pain, these numbers are comparable to TSCS; however, the improvements for distal pain are above TSCS benchmarks. This study clearly demonstrates the benefits of precise coverage of specific regions and of areas that aren’t easily covered by TSCS. More recently, Deer et al. published the results of an RCT of DRG stimulation versus TSCS for the treatment of lower extremity CRPS. The study included 152 patients who received either DRG stimulation or TSCS for the indication of CRPS. The percentage of subjects obtaining 50% pain relief was greater with DRG (81.2%) versus TSCS (55.7%, p < 0.001) at three months. These differences were noted at 12-month follow-up. Dorsal root ganglion stimulation also had greater improvements in quality of life and mood disposition, along with reduced postural variation in paresthesia coverage. The authors concluded that DRG stimulation provides more targeted therapy to the lower extremities and a higher percentage of treatment success than TSCS for lower extremity CRPS.
The third major advancement in SCS is the introduction of burst stimulation. During burst stimulation, periods of high-frequency impulses are delivered, specifically five pulses at 500Hz, 40 times per second. This mimics the natural central nervous system firing of neurons. In addition to the TSCS mechanism of action, burst stimulation has been proposed to affect the medial pain pathways and therefore affect the emotional components of pain interpretation. In a prospective, randomized, double-blind study by Schu et al. in 2014, the authors found that burst stimulation provided better pain relief than TSCS and was preferred by the majority of patients. Twenty patients who had previously been implanted with a TSCS system for the indication of FBSS, but had diminished response, were included in the study. The primary endpoint was pain intensity. Baseline mean NRS under conventional tonic stimulation was 5.6. The NRS while using burst stimulation was 4.7, which was statistically significant when compared to TSCS (P<0.05). Patients also preferred burst stimulation when compared to TSCS. They concluded that burst stimulation is an effective and safe SCS method in FBSS patients, particularly in patients with diminished response to previously implanted SCS, and was the preferred stimulation method over TSCS. In a 2017 study by Deer et al., 96 patients, mostly with FBSS and radiculopathies, were randomized to initiate SCS with either TSCS or burst stimulation. Following 12 weeks of the initial SCS method, the subject would begin the other stimulation parameters. The study was able to demonstrate that burst stimulation is non-inferior to tonic stimulation (p<0.001) and was superior to tonic stimulation for both trunk (p<0.013) and limb (p<0.045) pain intensity reduction. Also, similar to the prior study, more subjects preferred burst stimulation over TSCS (70.8%) due to lack of paresthesia and better pain relief, and this preference continued long term at one year. They concluded that burst stimulation was superior to TSCS for the treatment of FBSS and that a multimodal stimulation device capable of producing traditional and burst stimulation was advantageous for patient outcomes.
The technology surrounding SCS is rapidly transforming care for the chronic pain population. With advanced stimulation methods and targets, chronic pain physicians have been improving patient outcomes in neuromodulation. Both HF-10 and burst stimulation have proven more beneficial for pain reduction in FBSS compared with TSCS. Burst stimulation was also effective as a salvage procedure following loss of TSCS efficacy. Dorsal root ganglion stimulation has shown clinical improvements compared to TSCS in treating lower extremity CRPS and in obtaining targeted therapy not covered by TSCS, particularly in the distal extremities.
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