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Finding Optimal Neuromodulation
for Chronic Pain: Waves, Bursts, and
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Beyond
Manish Ranjan, Pranab Kumar1, Peter Konrad, Ali R Rezai
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Website:
www.neurologyindia.com

DOI: Abstract:
10.4103/0028-3886.302465
Background: Spinal cord stimulation (SCS) has emerged as state‑of‑the‑art evidence‑based treatment for
chronic intractable pain related to spinal and peripheral nerve disorders. Traditionally delivered as steady‑state,
paraesthesia‑producing electrical stimulation, newer technology has augmented the SCS option and outcome
in the last decade.
Objective: To present an overview of the traditional and newer SCS waveforms.
Materials and Methods: We present a short literature review of SCS waveforms in reference to newer
waveforms and describing paraesthesia‑free, high frequency, and burst stimulation methods as well as
advances in waveform paradigms and programming modalities. Pertinent literature was reviewed, especially
in the context of evolution in the waveforms of SCS and stimulation parameters.
Results: Conventional tonic SCS remains one of the most utilized and clinically validated SCS waveforms.
Newer waveforms such as burst stimulation, high‑frequency stimulation, and the sub‑perception SCS have
emerged in the last decades with favorable results with no or minimal paraesthesia, including in cases
otherwise intractable to conventional tonic SCS. The recent evolution and experience of closed‑loop SCS
is promising and appealing. The experience and validation of the newer SCS waveforms, however, remain
limited but optimistic.
Conclusions: Advances in SCS device technology and waveforms have improved patient outcomes, leading
to its increased utilization of SCS for chronic pain. These improvements and the development of closed‑loop
SCS have been increasingly promising development and foster a clinical translation of improved pain relief
as the years of research and clinical study beyond conventional SCS waveform come to fruition.
Key Words:
Conventional spinal cord stimulation, neurostimulation, new modalities of spinal cord stimulation,
paraesthesia‑free stimulation, SCS waveforms, subthreshold stimulation

Key Message:
Novel spinal cord stimulation waveforms have improved patient outcomes beyond conventional SCS waveform;
however, proper patient selection and selection of individualized waveforms remain critical to clinical translation
Department of
beyond long‑term study of the novel SCS waveforms.
Neurosurgery,
Rockefeller
Neuroscience
Institute, West Virginia
University, 1Department
T he initial efforts of spinal cord
stimulation (SCS) are attributed to Shealy
in 1967[1] following the seminal “gate‑control
showing favorable results in reducing intractable
pain of the back and limbs. We present a short
review of SCS literature in reference to recent
of Anaesthesiology and network’’ theory by Melzack and Wall in 1965.[2] innovations and clinical experiences with the
Pain Medicine, Toronto Since then, neuromodulation has evolved as a newer waveforms.
Western Hospital, state‑of‑the‑art, minimally invasive treatment
University of Toronto for attenuating chronic spinal and/or peripheral Background of SCS parameters and waves
nerve pain that is becoming evidence based. In In SCS, electrical stimulation that is applied
Address for the last decade, in addition to improvement through contacts located on the paddle or
correspondence: in electrode and controller (implanted pulse cylindrical electrode arrays placed in the posterior
Dr. Manish Ranjan, generator) design, a variety of options in epidural space overlying the spinal cord (typically
Department of
waveform shape and patterns have emerged in the lower thoracic region for treating back and
Neurosurgery, Rockefeller
Neuroscience Institute, leg pain and cervical region for treating neck
West Virginia University, This is an open access journal, and articles are distributed under the terms
33 Medical Center of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
How to cite this article: Ranjan M, Kumar P,
Drive, Morgantown, License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new Konrad P, Rezai AR. Finding Optimal Neuromodulation
WV ‑ 26505, USA. for Chronic Pain: Waves, Bursts, and Beyond.
creations are licensed under the identical terms.
E‑mail: drmanishranjan@ Neurol India 2020;68:S218-23.
gmail.com For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

S218 © 2020 Neurology India, Neurological Society of India | Published by Wolters Kluwer - Medknow
 Ranjan, et al.: Spinal cord stimulation - waves, bursts and beyond

and arm pain) [Figure 1]. Electrical current can be delivered Hz), high amplitude (3.6–10 mA), and pulsed wave (PW)
in a number of ways that are still being explored. The basic (300–600 μs).[3] The constant, low frequency stimulation induces
simulation parameters—frequency (Hz), pulse width (µsec), a noticeable tingling sensation called paraesthesia and the dogma
and amplitude (V or mA) are manipulated for the desired has been to superimpose paraesthesias on the patient‑specific
outcome.[3] More recently due to advances in implanted pulse region of pain for maximal pain relief.[7] Yearwood et al. showed
generator (IPG) technology, changes in shape, frequency, and that greater coverage, and some “caudal shift” of paresthesia
state (tonic versus burst) of the waveform have been tried coverage with increased PW that is accompanied by recruitment
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with varying success.[3] Impedance (ohms) is also commonly of larger number of Aβ‑fibers. [8] The amplitude impacts
measured by most IPGs and is a property mostly relating to the number of fibers recruited, and the strength duration
tissue healing around the implant. All these electrical parameters curve (SDC) for dorsal column fibers can be established by
(pulse, frequency, intensity, and impedance) are important determining the amplitude needed for paraesthesia perception
parameters that underlie the total energy being delivered to the and discomfort thresholds at increasing pulse width.[9] The
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patient and factor into the allowed safety limits of the device.[3‑5] resulting “therapeutic window” may guide SCS programming
for amplitude and pulse width to optimize pain relief while
Tonic conventional stimulation (TCS) or paraesthesia‑based minimizing discomfort.
SCS (PB‑SCS)
Since 1967, TCS also known as low‑frequency SCS (LF‑SCS) was Evolution of newer waveforms and paraesthesia‑free
the only stimulation paradigm available in clinical practice until SCS (PF‑SCS)
last decade. This stimulation paradigm is characterized by a PB‑SCS is an effective treatment option for chronic
steady sinusoidal wave [Figure 2a] with low frequency (40–120 neuropathic pain refractory to conventional medical
management (CMM).[10] Stimulation‑induced paraesthesias
may not be pleasant for all patients, and sometimes patients
do experience it beyond painful areas. This led to the
search of new programming modes of SCS that deliver
paraesthesia‑free stimulation such as burst SCS and high
frequency 10 KHz (HF10) SCS.

High‑frequency (HF) Stimulation: Traditionally the high

frequency can range anywhere from 1 KHz to 10 KHz (ultra‑high
frequency), but this has undergone reassignment to 5–10 KHz.[11]
A novel SCS device 10 KHz SCS (Nevro Corp) has been shown
to deliver short‑duration pulses (30 μs), high‑frequency
(10 kHz), low‑amplitude (1–5 mA) pulses [Figure 2b] to the
spinal cord without inducing any paraesthesia.[12] The HF10 SCS
can be placed anatomically between T8 and T11 vertebral levels
without the need for intraoperative paraesthesia mapping.[13]

BurstDR stimulation: Burst paradigm developed by De

Figure 1: Spinal cord stimulation lead position. The electrode (paddle or cylindrical) Ridder[14] consists of a 40‑Hz five impulse bursts (individual
sits in the posterior epidural space and the electrical stimuli activate fibers directly impulse at 1 ms duration and 1 ms interval) at an intraburst
below to it frequency of 500 Hz (or 1000 Hz) [Figure 2c]. The 500‑Hz

a b c d
Figure 2: Schematic concepts behind various stimulation waveforms used in SCS. The three parameters describing most waveforms are frequency (Hz), pulse width (µsec),
and amplitude (Volts or mA). (a) Traditional tonic spinal cord stimulation where stimulus frequency occurs at a steady rate. (b) High frequency usually refers to stimulation
rates over 1000 Hz. (c) Burst stimulation implies clusters of stimulation waves separated by pauses. (d) Sub‑perception stimulation is where the intensity is set below
perception threshold (reduced amplitude). (modified from Sheldon B et al.[6])

Neurology India | Volume 68 | Supplement 2 | November-December 2020 S219

 Ranjan, et al.: Spinal cord stimulation - waves, bursts and beyond

burst frequency (referred to simply as “burst”) is the primary conducted an RCT comparing burst SCS, tonic SCS, and
programming mode used in most studies. placebo in 15 SCS naive FBSS patients who were randomized
to receive each stimulation for a week. Burst SCS, but not
Sub‑perception SCS (SP‑SCS): Strategies using the multiple tonic SCS, significantly reduced global VAS scores but did
combinations of PW and frequency on the SDC can be not significantly reduce axial pain or limb pain VAS scores.[24]
manipulated to deliver large amounts of energy to the Similar positive results for burst stimulation was reported
dorsal column spinal structures without discomfort or by Schu et al., in their study conducting a sham‑controlled
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even a perceptible sensation.[3] Sub‑perception (SP‑SCS) randomized trial comparing burst SCS with both placebo
can be achieved utilizing frequencies between 1 KHz and 5 control, traditional (40 Hz) tonic SCS, and a continuous 500‑Hz
KHz [Figure 2d].[11] tonic paradigm in 20 patients with FBSS already receiving
PB‑SCS.[25] These findings were supported by Deer et al. in
Clinical utility and effectiveness of SCS waveforms SUNBURST RCT evaluating burst stimulation and TCS in
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Tonic SCS 100 patients. They reported superior pain relief for trunk pain
Studies have clearly demonstrated the medico‑economic and limb pain, and burst SCS was preferred treatment in 68%
interest and clinical efficacy of SCS.[15] TCS remains the most of patients at the end of one year open‑label phase period.[26]
widely used and studied technique in neuromodulation In a prospective study Vesper et al., studied microdosing
for pain. A randomized controlled trial (RCT) conducted in programs against standard burst for IPG energy conservation
complex regional pain syndrome (CRPS) by Kemler et al. strategy and found slightly higher satisfaction and preference
demonstrated higher pain relief and global perceived effect in with “microdosing” strategies but no significant advantage in
SCS along with physical therapy (PT) group than PT alone.[16] terms of pain relief.[27]
North et al. in EVIDENCE study compared SCS to repeat lumbar
spine surgery in failed back surgery syndrome (FBSS) and High frequency stimulation
concluded favorably for SCS obviating the need for reoperation A double‑blind, sham‑controlled HF‑SCS (HF 5 KHz) study
in the majority of patients.[17] Kumar et al., compared SCS in of 40 patients found promising results with Patient Global
PROCESS RCT with CMM in FBSS population. SCS proved Impression of Change in favor of HF‑SCS compared to sham
superior for alleviating leg pain and improved quality of life stimulation.[28] The pivotal SENZA‑EU study conducted by
at 6, 12, and 24 months.[10] TCS was compared to CMM in Van Buyten and Al‑Kaisy et al. enrolled 83 subjects with
patients with painful diabetic peripheral neuropathy in two significant axial low back pain. 60% of the implanted patients
prospective RCTs. These studies demonstrated not only the had at least 50% back pain relief and 71% had at least 50% leg
superiority of neuromodulation over CMM but also one of the pain relief (follow‑up to 24 months in 90% of patients).[29,30]
trials showed sustained improvement in pain relief in the SCS Kapural et al. to assess the non‑inferiority of HF 10 KHz over
group at 5 years.[18,19] Rigoard et al. in a large multicenter trial TCS conducted the Food and Drug Administration‑approved
compared multicolumn SCS along with the optimal medical SENZA RCT which demonstrated superiority of 10 KHz
management (OMM) to OMM alone in FBSS with predominant compared to TCS treatment in 198 patients with axial
low back pain, and showed the significantly improved back and/or leg pain (66.9%, 65% Vs 41.1%, 46%) with 1:1
pain relief, quality of life, and function in a traditionally randomization at 24‑month follow‑up.[31,32] A post hoc analysis
difficult‑to‑treat population, and theses outcomes were of the two studies SENZA‑EU and SENZA‑RCT reported an
maintained at 24 months.[20] The clinical experiences and the average reduction of opioid use by 46% in high‑risk category
evidences from the clinical trials established SCS, specifically patients with ≥90 morphine milligrams equivalent presenting
TCS as one of the best evidence‑based cost‑effective treatment with leg pain and/or low back pain at 12 months of HF10
to treat certain refractory neuropathic pain conditions. SCS therapy.[33] A proof‑of‑concept study evaluating HF10
stimulation in 20 patients with low back pain who were
Burst SCS not surgical candidates, reported pain VAS and Oswestry
The first peer‑reviewed evidence on burst SCS was published Disability Index scores reduction to an average of 73% and 48%
by De Ridder et al. in 2010 who demonstrated significant from baseline at 12 months.[34] Follow‑up data at 36 months
reduction of axial back and limb visual analog scale (VAS) from 17 patients showed significant sustained reductions
scores at 12‑month follow‑up in 12 patients.[14] In an open‑label in back pain VAS scores with 88% of patients not taking
short‑term multi‑site study, Courtney et al. investigated the opioids.[35] Similar to these experiences, an Australian study
effect of burst stimulation in 22 subjects who were previously from three large pain clinics reported higher trial conversion
using TCS for at least 90 days. Significant reductions in global, rate with HF stimulation. The numeric rating scale scores for
trunk, and limb pain was reported during burst SCS with the entire cohort were significantly reduced for six months and
majority of the patients preferring burst stimulation over even prior non‑responders with TCS also reported positive
TCS.[21] Higher frequency burst stimulation (1000 Hz) against outcomes with HF stimulation.[36] However, results are not
the standard burst (500 Hz) was explored in another study, uniformly favorable with burst stimulation across all the
however, no significant difference in back pain, limb pain, or studies. Kinfe et al. performed a prospective observational
general pain scores were reported between standard burst and study in 16 SCS‑eligible FBSS patients to receive either
high frequency burst frequencies.[22] de Vos et al. conducted burst or HF10 SCS. Study reported no differences between
a 2‑week burst SCS study of 48 patients who had already the modalities in back pain, though leg pain was better
received tonic SCS treatment for a period of at least 6 months controlled with burst SCS.[37] In one non‑industry‑funded
for mixed pain states (painful diabetic neuropathy, FBSS, study, investigators compared HFS with TCS in 60 patients
FBSS who were poor responders to tonic SCS) and concluded and reported minimal difference between the two groups at
favorably for burst stimulation.[23] In 2013, De Ridder et al. one year.[38]

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 Ranjan, et al.: Spinal cord stimulation - waves, bursts and beyond

Sub perception SCS evidence. [48‑52] Importance of placebo‑responders and

Clinical experiences with the sub‑perception SCS have been sham‑effects in neuromodulation in clinical trials must not be
favorable as well. North et al. compared LF‑SCS (50 Hz) to underestimated.[53] There is need for a better designed study
SF‑SCS (1 KHz) in a prospective RCT and found 95% of patients and transparency in the reporting, this especially hold true
showed improvement in numeric rating scale scores, with pain as many of SCS studies are industry sponsored. And above
relief better in 1 KHz cohort.[39] PROCO RCT, a double‑blind all, sometimes patient preference or beliefs dominate over
crossover study evaluating different frequencies from 1 to the science behind the SCS waveform or the device selection,
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10 kHz (1,4,7,10) in a cohort of 33 patients with 4 weeks at as reported by Duse et al., where 50% of patients in their
each frequency, which followed with a 3‑month open‑label series of 28 FBSS patients preferred PB-SCS due to the belief
phase allowing patients to choose their favorable frequency. the functioning of SCS corresponded with the perception of
Majority (50%) of patient chose 1 kHz, followed by 7 kHz (25%), paresthesia.[54] Although literature does not unanimously
10 kHz (15%), and 4 kHz (10%). Interestingly, the overall pain support one waveform over other especially study evaluating
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reduction was sustained independent of chosen the stimulation different waveforms[55] nevertheless, the advanced waveforms,
frequency.[40] In WHISPER trial, the investigators compared pulse trains, and programming capabilities have expanded the
sub perception <1.2 KHz with supraperception stimulation, clinical utility of SCS.
and found significant improvement in pain relief with SP‑SCS
at 12 months, with positive outcomes in subjects who were Conclusions
paresthesia failures with previously implanted SCS patients.[41]
Chronic pain is a dynamic condition characterized by diverse
Advanced programming of SCS waveforms in IPG platforms patterns and variable severity over time. Early and pivotal
Various new algorithms and technological advances came up studies evaluating tonic SCS laid the foundations of the
in the field of SCS to optimize the energy/electrical response evidence in the field of neuromodulation, and since then
and improve the outcome. High‑dose (HD) stimulation neuromodulation has had rapid technological advancements.
allows large amounts of charge to be administered at the Newer paraesthesia‑free modes of SCS may provide an SCS
extreme ends of the curve (either narrow or wide PW), salvage strategy for tonic SCS patients experiencing loss of
remaining below threshold (sub‑perception) and thus avoiding efficacy over time or maybe preferred over TCS by patients/
“stimulation‑induced paraesthesia”[42] and expanding to patient clinicians. Although there is no consensus for the ideal SCS
population who are otherwise intolerant to SCS‑induced waveform or stimulation, the newer SCS waveform, pulse
paresthesia.[42,43] “Duty cycle” strategies have evolved using trains, or central axial targets have been shown to be beneficial
multiple combinations of PW and frequency on the SDC to for certain pain states, however, stringent patient selection
deliver large amounts of energy to the spinal structures in along with patient participation and education remains
the dorsal column without discomfort or even a perceptible critical for the success of the individualized SCS therapy. The
sensation.[3] Medtronic’s Evolve SM Workflow Algorithm platform accumulated clinical evidence demonstrated the newer SCS
from Intellis uses technology that can deliver both HD waveforms are generally favorable giving additional options
(1000 Hz, 90µs) and low‑dose stimulation through an overdrive for the patient and the clinician. With all these variables, the
IPG and intrinsic accelerometer.[44] Boston Scientific’s provides proper understanding of waveforms and the selection of an
“WaveWriter TM” technology, which has an ability to layer ideal SCS system is more crucial than ever for an optimal
tailored complex broad‑spectrum sub‑perception waveforms clinical outcome. Larger controlled studies are needed to
and low‑frequency stimulation via an interactive feedback validate the application of specific SCS waveforms to facilitate
feature. The multiple‑independent power sources (MICC individualized SCS therapy for complex pain disorders.
technology) and anode intensification refine better control
of the current delivery to each contact of SCS electrode for Financial support and sponsorship
better neural targeting and electrical plasticity.[45] Recently, Nil.
closed‑loop spinal cord stimulation (Saluda Medical) was
introduced to automatize the energy output based on the Conflicts of interest
evoked compound action potentials with a significant There are no conflicts of interest.
improved outcome.[46,47]
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