Burst stimulation has been studied extensively. In a double-blind placebo-controlled trial comparing tonic stimulation with burst stimulation with placebo, burst stimulation statistically significantly improved pain reduction for general pain, back pain, and leg pain [19]. Additionally, at clinically useful amplitudes, burst stimulation waveform provided analgesia without a reliance on perceived paresthesia [18]. In another study, patients that had traditional, tonic stimulation for at least 6 months were given burst stimulation for 2 weeks. The patients were grouped into three categories: diabetic peripheral neuropathy (DPN) , failed back surgery syndrome (FBSS) , and FBSS-poor responders (FBSS-PR) . FBSS-PR was defined as patients with failed back surgery syndrome plus poor or lost therapeutic benefit from their SCS device. Interestingly, the visual analog scale (VAS) was reduced nearly 62 % on average with burst-SCS compared to 37 % with SCS. Additionally, the effect compared to tonic stimulation was largest for PDN (decreased 77 %), as compared to FBSS (decreased 57 %), or FBSS-PR (23 %) [21]. Another study similarly examined previously SCS-implanted patients and intervened with 2 weeks of burst stimulation [22]. VAS reduced 46 % with the burst stimulation with 73 % of the patients reporting no paresthesia while 23 % reported a reduction. Overall, 91 % preferred the burst stimulation. A prospective, randomized, double-blinded, placebo-controlled study examined the burst stimulation to 500 Hz tonic stimulation and to placebo stimulation in FBSS subjects [23]. Overall, burst stimulation resulted in significantly better pain relief and improved pain quality. It is important to note that since burst stimulation has energy requirements that are usually less than traditional tonic stimulation, primary or rechargeable battery can be used.

No complications were reported to be associated strictly with burst-SCS. Recently, a randomized multicenter comparative efficacy study evaluating burst to tonic stimulation has been fully enrolled in the USA under FDA pivotal monitoring (Sunburst, St. Jude Neuro division, Plano, Texas). The results of this study, which has a non-inferiority design, should be available by the fall of 2015.

HF10 therapy is another advance heralded as providing analgesia without paresthesia. HF10 (Nevro, Menlo Park) is capable of delivering frequencies from 2 to 10,000 Hz but the therapy is always delivered at 10,000 Hz compared to the 40 to 100 Hz typically used in conventional SCS. At this time, it is the only FDA-approved paresthesia-free therapy. HF10 therapy uses biphasic charge-balanced pulse train with pulse widths usually set to 30 microsecond and a uniform frequency (Fig. 21.2). Like all forms of SCS it has been theorized that HF10 therapy may also impact both spinal and supraspinal mechanism pathways, but the mechanism of action is not currently fully elucidated. Preclinical work in animal models suggests the ability of HF10 SCS to suppress hypersensitized wide dynamic range cells [24].

Several studies have shown HF10 to be efficacious in treatment of chronic pain. One studied predominant back pain patients, who were trialed sequentially with traditional SCS and then HF-10 SCS [16]. At the end of the sequential trials, HF10 stimulation reduced VAS 77 % from baseline, with a responder rate of 83 %, while traditional SCS had a VAS reduction from baseline of 55 %, with a 58 % responder rate. 88 % preferred HF10 over traditional SCS. Although HF10 performed better than traditional SCS, both methods significantly produced a reduction in baseline pain. A European multicenter trial yielded similar findings [25, 26]. Patients were implanted with HF10 SCS and followed for 6 months [25]. 88 % of the patients trialed with HF10 were converted to the permanent therapy. At 6 months, the average baseline back pain VAS was improved to 2.4 from 8.4. The ODI at 6 months improved to 37 from 55. Of note, 74 % of the patients at 6 months were defined as responders (having a greater than 50 % VAS improvement in their pain) and 85 % of the patients reported satisfaction with HF10. This study also showed improvement in the use of opioids. Of the 86 % of the patients who were using opioids at baseline, 38 % eliminated their need for opioids and 62 % reduced them. At 24 months, average VAS back pain was 3.3 from 8.4 and leg pain 2.3 from 5.4 [26]. Finally, a multicenter, prospective, randomized, controlled trial (SENZA-RCT) showed that 84.5 % of implanted HF10 therapy subjects were responders for back pain and 83.1 % for leg pain. In comparison, in the controlled group consisting of traditional SCS subjects, 43.8 % were responders for back pain and 55.5 % for leg pain. The superiority of the paresthesia-free HF10 group continued to show superiority at 12 months [27].

In a study in Switzerland, investigators studied stimulation at 5 kHz to sham (no stimulation) and tonic stimulation in a double-blind, two period crossover, randomized control trial [28]. They reported that only 14/33 patients responded to the 5 kHz stimulation, and the 5 kHz stimulation was equivalent to sham for primary outcome measures. This may suggest that the results are inherently dependent on the frequency used for stimulation, and not all high-frequency stimulation is equal. The study had many questions on method however such as lead placement, preconditioning to tonic stimulation, and patient selection that many feel no valid conclusions can be made. HF10 stimulation requires a much higher energy burden as compared to conventional or burst stimulation. There is no evidence that this may impact battery life but daily charging is required. With the constraints of current battery technology, HF10 stimulation at this time is used with rechargeable technology. Since the HF10 SCS stimulation does not require a paresthesia for analgesia, and based on years of empirical work programming patients, the area of stimulation for this therapy is between T8 and T11, and the leads can be placed with the implant procedure performed with the patients in continual sedation with placement based on anatomical landmarks in the midline.

The complication rate of the HF10 appears to be the same as compared to traditional SCS, and there is no evidence in the human or animal that higher frequencies cause neural damage.

Dorsal root ganglion (DRG) stimulation involves placement of a novel electrode lead on the surface of the DRG. The DRG contains cell bodies of primary sensory neurons. There are several types of DRG neurons and they are known to participate in the signaling process as well as modulation of this process [29]. This includes sensory processing of nociceptive pain and the development of neuropathic pain. As a result, the DRG has long been a clinical target for pain control, most recently with neuromodulation [30–39]. The location of the DRG is consistent and is always in the epidural space between the medial and lateral aspects of the pedicle with the neural foramen and is made up of the dorsal sensory root fiber cell bodies as dorsal afferent sensory axons and ventral efferent motor axons form the respective rootlets. The DRG is accessed for neurostimulation from an epidural approach using a DRG lead-specific sheath (Fig. 21.3). The DRG lead is much smaller than conventional leads and has a unique shape. It is theorized that electrical stimulation around the DRG may decrease hyperexcitability of the DRG neurons and thereby provide relief of chronic aberrant pain.

DRG stimulation was initially studied in a prospective, single-arm, pilot study [37]. The results showed 70 % overall reduction in pain as well as reduction in pain medication use. Pain relief in the foot was even more vigorous at over 80 %, which is encouraging considering that this can be a difficult target with conventional dorsal column stimulation. A larger multicenter prospective trial studied DRG stimulation in chronic pain of limb and/or trunk [38]. At 6 months, average overall pain ratings were 58 % lower than baseline, with more than half the subjects reporting greater than 50 % relief. The proportions of subjects experiencing 50 % or more reduction in pain specific to back, leg, and foot regions were 57 %, 70 %, and 89 %, respectively. The study had two reversal periods in which the stimulation was turned off, during which time, the pain returned to baseline levels. Furthermore, the results showed stable paresthesia intensity over time with no significant difference in the paresthesia intensity perceived during different body postures/positions (standing up vs. lying down). The subjects continued to experience benefit at 12 months [40]. Pain was reduced by 56 % at 12 months post-implantation, and 60 % of subjects reported greater than 50 % improvement in their pain with DRG stimulation. Pain localized to the back, legs, and feet was reduced by 42 %, 62 %, and 80 %, respectively.

In addition to pain improvement and stable paresthesia intensities independent of body position, DRG stimulation may be better able to capture discrete painful areas such as the feet or groin [41, 42]. DRG stimulation modality may allow for more selective and consistent targeting of painful areas than conventional SCS.

DRG stimulation has been attempted with conventional SCS systems; however currently approved systems are large and may compress the DRG within the foramen. Additionally, the size and spacing of the electrodes are not designed to target the DRG and may recruit and stimulate other structures. The new system is specifically designed to address these issues, to safely, comfortably, and optimally stimulate the DRG.

In the 12-month prospective study, the most common adverse events were temporary motor stimulation, cerebral spinal fluid leak with associated headaches, and infection. The two most frequent adverse events were attributed to implant procedure and programming of the novice device and technique. The infection rates were comparable to conventional published rates.

Recently, the results of the US pivotal study on DRG stimulation as compared to conventional stimulation were presented at the International Neuromodulation Society meeting [43]. In this FDA-monitored study, DRG showed both non-inferiority and superiority as compared to conventional spinal cord stimulation in the treatment of neuropathic pain of the groin and lower limb [44].