Research Article

For reprint orders, please contact: reprints@futuremedicine.com

BurstDR spinal cord stimulation in the

treatment of chronic visceral pain
Ganesan Baranidharan*,1,2 , Beatrice Bretherton1,3 , Thomas Kay2 , Nathan Marsh2 ,
Charlotte Romanis2 & Bethan Roberts2
1
Department of Pain Management, Leeds Teaching Hospitals NHS Trust, Leeds UK
2
School of Medicine, Faculty of Medicine & Health, University of Leeds, Leeds UK
3
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds UK
*Author for correspondence: g.baranidharan@nhs.net

Background:Visceral pain can be disabling for patients and challenging to treat in the clinic. Spinal cord
stimulation is a NICE approved treatment for chronic neuropathic pain, presenting potential advantages
over conventional therapies for managing chronic visceral pain. Results: A retrospective study revealed
that a specific type of spinal cord stimulation, BurstDRTM (Abbott, TX, USA), was effective at improving
pain and quality of life in patients with chronic visceral pain. Baseline pain scores significantly correlated
with change at follow-up, suggesting it may be possible to identify potential responders from the outset.
BurstDR was safe: rates of revision, explantation and complications were low. Conclusion: Clinical trials
exploring the long-term effects of BurstDR including a control arm are needed. Findings could have the
potential to inform best practice and improve outcomes for individuals with chronic visceral pain.

First draft submitted: 24 March 2019; Accepted for publication: 22 May 2020; Published online:
21 August 2020

Keywords: BurstDR • explantation • health-related quality of life • infection • IPG site • response • revision • spinal
cord stimulation • visceral pain

Visceral pain can be a debilitating condition, having negative effects on an individual’s life, including their
employment, relationships and hobbies. Visceral pain arises when there is damage to internal organs including the
stomach, pancreas, bowel, kidneys and pelvic organs. Inflammation, a lack of blood flow (ischemia) and/or the
accumulation of fluid or gas (distention) are potential mechanisms of visceral pain. This subsequently leads to the
activation of sensory afferents and the experiencing of pain which tends to be characterized by acute exacerbations
layered on top of a constant background pain [1].
Visceral pain is considered to be one of the most common types of pain. For instance, abdominal pain is reported
by 25% of adults [2], with nonspecific abdominal pain being the tenth most common cause of hospitalization in
men and the sixth most common cause in women [3]. Abdominal pain is associated with high healthcare utilization,
resulting in high healthcare costs [4]. Interestingly, 5 years following initial presentation, abdominal pain has been
found to disappear in around 43% of men and 31% of women [5]. Other presentations of visceral pain, such as
chest pain and pelvic pain, are also frequently reported in adults, with a prevalence rate of 20% for chest pain and
pelvic pain occurring in 16–24% of females [3]. Individuals with visceral pain may have dysfunction in more than
one organ, resulting in multiple and complex symptoms. As a result, this makes it difficult to determine the cause
of the pain and the most effective treatment [6].

Current treatments for visceral pain

Due to the potential complexity of individual cases, visceral pain can be challenging to treat. Current therapies
typically involve pharmacological interventions which aim to help patients manage their pain. As visceral pain is
being increasingly viewed as a neuropathic pain condition, as opposed to a nociceptive pain condition, drugs that are
effective for treating chronic neuropathic pain are being used. This includes drugs such as, gabapentin, pregabalin
and amitriptyline. However, there are very few drugs which have been approved for the specific treatment of visceral

10.2217/pmt-2020-0014 
C 2020 Future Medicine Ltd Pain Manag. (2020) 10(5), 319–329 ISSN 1758-1869 319
Research Article Baranidharan, Bretherton, Kay, Marsh, Romanis & Roberts

pain. For instance, although Elmiron (pentosan polysulfate sodium) is used to relieve bladder pain resulting from
interstitial cystitis, it is not used to treat visceral pain per se [6]. Opioids also play a significant role in managing
visceral pain. However, the doses used and the length of opioid use have little supportive evidence. Additionally,
with the opioid aware campaign, opioids are not a viable option to manage long-term pain. Undesirable side
effects are frequently associated with pharmacological therapies that are being used to manage chronic visceral
pain. In response, there has been an increasing demand for safer and more effective treatments that have minimal
complications.
As visceral pain is closely tied to the autonomic nervous system with there being a large sympathetic component [7],
techniques that block autonomic function are being delivered to reduce visceral pain. This includes celiac plexus
blocks which promote pain relief and help determine whether the pain is visceral or from another origin [1]. In
addition, for those who encounter limited improvements in their pain following a celiac plexus block, splanchnic
nerve blocks can be used. This is similar to the celiac plexus block with the exception that the needle is placed more
toward the head, resting at the anterolateral margin of the T12 vertebral body, aiming at the preganglionic fibers [8].
Thoracoscopic splanchnectomy and splanchnic radio frequency involve destructive lesion to these preganglionic
fibers. This reduces the activity of nerves that carry pain signals to the brain by creating a heat lesion on the target
nerve. Since these techniques have limited long-term pain relief [9], there is a clear clinical need for a treatment that
is effective in both the short and long term, has a strong safety profile and can reduce healthcare utilization in this
patient group.

Spinal cord stimulation: a potential treatment for visceral pain?

Spinal cord stimulation (SCS) is a treatment for chronic pain of neuropathic origin. It consists of an implantable
device made of a medical wire passed into the spine via a needle and connected to a battery (implantable pulse
generator [IPG]) inserted under the skin. SCS has been shown to significantly reduce pain in individuals with
failed back surgery syndrome [10], fibromyalgia [11], complex regional pain syndrome [12], and painful diabetic
neuropathy [13]. In recent years, this field of neuromodulation has observed technological advances to improve
outcomes. This has included the development of new stimulation parameters that can be tailored to the needs of
patients. One of these new approaches is BurstDRTM (Abbott, TX, USA). Unlike traditional tonic SCS, which
delivers consistent stimulation at relatively low frequencies (e.g., 30–70 Hz) and relies on paresthesia to mask the
pain, BurstDR is a paresthesia free approach, delivering groups of pulses separated by short pulse-free periods to
dorsal columns in the spinal cord. Stimulation parameters are typically characterized by five 1 ms pulses with an
internal frequency of 500 Hz delivered at 40 Hz using a passive recharge pattern and waveform [14].
BurstDR first emerged as a treatment for tinnitus and has since been applied to pain medicine [14,15], with
promising clinical evidence [16,17]. For instance, effectiveness has been demonstrated in chronic pain conditions
such as, failed back surgery syndrome [18–24], failed neck surgery syndrome [18], myelopathy and myelomalacia [18],
complex regional pain syndrome [25] and painful diabetic neuropathy [19,24]. Intriguingly, microdosing paradigms
can be implemented in BurstDR, where 5 or 10 s of stimulation are delivered followed by 5 or 10 s of no
stimulation [26]. Indeed, patients have reported higher satisfaction and preference for microdosing paradigms
compared with standard BurstDR [26]. The advantage of this technique over standard BurstDR, and indeed other
SCS systems, is that the battery life is prolonged while also offering effective pain relief. Clearly, this evidence shows
that BurstDR is effective in chronic neuropathic pain conditions and therefore points to the promising potential
of using BurstDR to treat chronic visceral pain.

Clinical efficacy, safety & tolerability of SCS in visceral pain

Evidence for the efficacy of using SCS in visceral pain typically comes from case reports and cohort studies
(see Table 1 for a summary). Findings consistently illustrate that SCS, in the visceral pain conditions studied, is
associated with improvements in pain [1,27–38], pain-related disability [30,34,36], quality of life (QoL) [1,27] and global
impressions of change [1]. In addition, some studies have reported decrease in medication consumption [1,27,29–
36,38] and patients returning to work [37]. SCS in visceral pain conditions also appears to have a good safety profile
and is well-tolerated by patients. The most commonly reported complications include infection [1,31,33] and lead
migration [29–31,33,35,38], with autonomic-related effects (e.g., headache and diarrhea [32]) being less commonly cited
(see Table 1 for a summary). Findings from these early clinical trials therefore establish an initial evidence base
demonstrating that SCS is effective, safe and well-tolerated in individuals with chronic visceral pain.

320 Pain Manag. (2020) 10(5) future science group

 BurstDR spinal cord stimulation in the treatment of chronic visceral pain Research Article

Table 1. Summary of research investigating the efficacy of spinal cord stimulation in visceral pain conditions.
Published research Sample size (n) Visceral pain conditions treated Spinal cord Outcomes Complications Ref.
(year) stimulation
Baranidharan 26 PSIAA, CP, IBD Dorsal and ↓ pain and medication Infection [1]
et al. (2014) ventral consumption. ↑ QoL and PGIC
Ceballos 1 (case report) MI Medtronic ↓ pain and medication None [27]
et al. (2000) consumption. ↑ QoL
Jackson & 1 (case report) Chronic oesophageal dysmotility Medtronic ↓ pain None [28]
Simpson (2004)
Kapur et al. (2006) 2 (case reports) Familial Mediterranean fever ANS, Precision ↓ pain and medication Lead migration [29]
consumption. Returned to work
Kapural et al. (2006) 6 (case series) Visceral pelvic pain Medtronic ↓ pain, pain disability and Lead migration [30]
medication consumption
Kapural et al. (2010) 30 MI, gastroparesis, CP & PSIAA St Jude, Boston ↓ pain and medication Infection, lead [31]
Scientific consumption migration
Kapural et al. (2010) 76 (case reports) Gastroparesis, CP & PSIAA NS ↓ pain and medication Headache, [32]
consumption diarrhea
Kapural et al. (2011) 30 CP NS ↓ pain and medication Infection, lead [33]
consumption migration
Kapural & 1 (case report) CP ANS ↓ pain, pain disability, None [34]
Rakic (2008) medication consumption
Khan et al. (2005) 9 (case reports) Post-traumatic splenectomy & CP Medtronic, ANS ↓ pain and medication Lead migration [35]
consumption
Kim et al. (2009) 1 (case reports) CP ANS ↓ pain, pain disability and None [36]
medication consumption.
Returned to work
Krames & Mousad 1 (case reports) IBS Medtronic ↓ pain None [37]
(2005)
Tiede et al. (2006) 2 (case reports) Gastroparesis ANS ↓ pain and medication Lead migration [38]
consumption
↓: Decrease; ↑: Increase; ANS: Advanced neuromodulation system; CP: Chronic pancreatitis; IBD: Irritable bowel disorder; IBS: Irritable bowel syndrome; MI: Mesenteric ischemia;
NS: Not stated; PGIC: Patient global impression of change; PSIAA: Postsurgical intra-abdominal adhesion; QoL: Quality of life.

To develop these preliminary findings, future research could undertake larger clinical trials investigating the
effects of BurstDR in a specific chronic visceral pain condition. Indeed, most prior research has used other types of
SCS and focused on more than one chronic visceral pain condition. In response to this, there is an ongoing single
center, prospective, randomized, crossover, controlled, feasibility research trial investigating the effects of BurstDR
in individuals with visceral pain secondary to chronic pancreatitis. Chronic pancreatitis affects approximately four in
100,000 individuals in the UK and USA [39]. Severe abdominal pain is the predominant symptom, characterized
by a constant background pain and acute episodes needing hospital admission. This pain normally persists for
the full duration of the disease, resulting in a high pain burden, hospital (re)admissions and general practitioner
(GP) appointments, which put pressure on healthcare services. Given that chronic pancreatitis cannot be cured
completely, most treatments focus on managing the severe pain, often with limited effectiveness and many side
effects. Treatments typically include lifestyle changes (e.g., avoiding alcohol, smoking and adopting dietary changes),
pain killers and surgery. It is hoped that findings from this study will provide the first evidence on the efficacy and
safety of using BurstDR to enable individuals to better manage the persistent visceral pain associated with their
chronic pancreatitis.

Regulatory affairs
In the UK, SCS is currently a NICE approved treatment for chronic pain of a neuropathic origin (TA159). NICE
also provides guidelines on the pharmacological management of neuropathic pain (CG173). This recommends
that patients with neuropathic pain (except trigeminal neuralgia) are offered a choice of amitriptyline, duloxetine,
gabapentin or pregabalin as an initial treatment which is then switched to one of the other drugs if relief is not
achieved. For localized neuropathic pain, capsaicin creams to avoid oral treatments can be administered. NICE
recommends that for adults with chronic visceral pain secondary to chronic pancreatitis that the guidelines for
treating neuropathic pain are followed. The US FDA approved SCS in 1989 and CE mark has been granted for

future science group www.futuremedicine.com 321

Research Article Baranidharan, Bretherton, Kay, Marsh, Romanis & Roberts

Table 2. Summary of the characteristics for the full sample.

Initial information Total sample (n) 47
Females (n) 22
Age (mean ±1 SEM, years) 48.19 ± 1.55
Diagnosis Chronic pancreatitis (n) 23
Multiple surgeries (n) 11
Other (n) 12
Status Failed trial (n) 1
Awaiting implant following successful trial (n) 1
Awaiting first follow-up (n) 1
PANACEA trial (n) 12
Full system explants (n) 3
SEM: Standard error of the mean.

Table 3. Summary of initial characteristics for the final sample.

Initial information Total sample (n) 29
Females (n) 16
Age (mean ±1 SEM, years) 48.62 ± 2.04
Diagnosis Chronic pancreatitis (n) 10
Multiple surgeries (n) 9
Other (n) 10
IPG location Chest wall (n) 13
Buttock (n) 4
Flank (n) 5
Abdomen (n) 2
Missing data (n) 5
IPG: Implantable pulse generator; SEM: Standard error of the mean.

a number of those SCS devices, in the USA. The devices used in this study (Abbott) are FDA approved for the
treatment of intractable pain of trunk and extremities.

BurstDR in visceral pain: real-world evidence from Leeds Teaching Hospitals NHS Trust
From the reviewed research, there appears to be limited evidence into the effectiveness and safety of BurstDR
in chronic visceral pain conditions. In response, the current study retrospectively explored the efficacy and safety
of BurstDR in individuals with chronic visceral pain conditions at the Leeds Teaching Hospitals NHS Trust.
The study aimed to investigate how pain and health-related quality of life (HRQoL) changed with BurstDR in
individuals with a chronic visceral pain condition. Rates on complications, surgical revisions and explantations
were also ascertained.

Patients & methods

Following approval of the local institutional review board, 47 individuals (n = 22 females) with chronic visceral
pain received BurstDR in the Leeds Teaching Hospitals NHS Trust between 2013 and March 2020 (see Table 2
for a summary). The predominant diagnosis was visceral pain secondary to chronic pancreatitis (n = 23). There
was one failed trial, one patient was awaiting a full system implant following a successful trial, another was awaiting
their first follow-up following a full system implant and 12 patients were enrolled on the PANACEA trial (findings
will be presented in due course). Three patients had their full system explanted.
The final sample consisted of 29 individuals (n = 16 females) with chronic visceral pain who received a fully
implanted BurstDR system (see Table 3 for a summary). Visceral pain secondary to chronic pancreatitis comprised
around 34% of the sample. IPGs were most frequently implanted in the chest wall, followed by the flank, buttock
and abdomen. IPG information was missing in five cases.

322 Pain Manag. (2020) 10(5) future science group

 BurstDR spinal cord stimulation in the treatment of chronic visceral pain Research Article

10 10
Average pain (VAS)

Worst pain (VAS)

8 8

6 * 6

4 4

2 2

0 0
Baseline Follow-up Baseline Follow-up

0.5
*
0.4
HRQoL (EQ-5D)

0.3

0.2

0.1

0.0
Baseline Follow-up

Figure 1. Change in pain and health-related quality of life with BurstDR. Average pain (A), worst pain (B) and
health-related quality of life scores (C) significantly improved between baseline and follow-up (530.90 ± 84.52 days).
*Significantly different to baseline. Data presented as the mean ±1 SEM.
HRQoL: Health-related quality of life, measured using the EQ-5D; SEM: Standard error of the mean; VAS: Visual
analog scale.

Data collection & analysis

The following data were ascertained from paper files and hospital electronic records: gender, diagnosis, trial outcome
(success or failure), implant date, site of implant and the occurrence of revisions, explants as well as complications.
Scores for average and worst pain (ascertained via visual analog scales) and HRQoL (assessed by the EQ-5D
questionnaire) were ascertained from baseline and the latest follow-up visit.
Statistical analysis was performed in SPSS (version 25) and normality was ascertained via the Shapiro–Wilk test.
All tests were two-tailed and an alpha level of 0.05 was deemed statistically significant. Paired sample t-tests (or
Wilcoxon signed-rank tests for non-normally distributed data) explored differences in average pain, worst pain and
HRQoL between baseline and follow-up. A Pearson correlation explored the relationship between baseline average
pain and change () at follow-up. Independent sample t-tests (or Mann–Whitney U tests) compared differences
between responders (≥50% improvement in average pain) and nonresponders (<50% improvement in average
pain). Rates of revision, explantation and complications were ascertained.

Results
Pain & QoL improved with BurstDR
Average pain (baseline 95% CI: 6.60–7.72; follow-up 95% CI: 3.21–5.28; p = 0.001), worst pain (baseline
95% CI: 8.49–9.37; follow-up 95% CI: 5.31–7.38; p < 0.001) and HRQoL (baseline 95% CI: -0.03–0.26;
follow-up 95% CI: 0.14–0.56; p = 0.025) were significantly improved at follow-up compared with baseline (see
Figure 1). Mean (±1 standard error of the mean [SEM]) follow-up duration was 530.90 ± 84.52 days (95% CI:
357.77–704.02 days).

Baseline average pain correlated with response to BurstDR

A Pearson correlation revealed that baseline average pain was significantly related to change () at follow-up
(r = -0.484, p = 0.008, see Figure 2). Indeed, high average pain at baseline was related to greater decreases in average
pain at follow-up. Individuals were then classified into one of two groups (responder or nonresponder) according to
the magnitude and direction of change in average pain between baseline and follow-up. Responders showed ≥50%

future science group www.futuremedicine.com 323

Research Article Baranidharan, Bretherton, Kay, Marsh, Romanis & Roberts

4
2
Δ average pain 0
-2 2 4 6 8 10
-4
-6
-8 Figure 2. Baseline average pain significantly correlated with
-10 change (, between baseline and follow-up,
Baseline average pain r = -0.484; p = 0.008).
VAS: Visual analog scale.

10 10
Average pain (VAS)

Average pain (VAS)

8 8

6 6

4 4

2 2

0 0
Baseline Follow-up Baseline Follow-up

Figure 3. Average pain during baseline and follow-up for responders (A, ≥50% improvement) and nonresponders
(B, <50% improvement). Solid black line indicates group mean.
VAS: Visual analog scale.

improvement in average pain between baseline and follow-up and nonresponders showed <50% improvement. In
total, there were 13 responders (mean age ±1 SEM: 47.85 ± 2.85 years; n = 10 females) and 16 nonresponders
(mean age ±1 SEM: 49.25 ± 2.96 years; n = 6 females), resulting in a response rate of 45%.
Figure 3 plots individual and group mean (in black dashed line) changes in average pain between baseline
and follow-up. In the group of responders, average pain was significantly reduced at follow-up (95% CI: 0.71–
2.52) compared with baseline (95% CI: 6.49–8.36; p = 0.001). Although, no significant differences in average pain
between baseline (95% CI: 6.33–7.67) and follow-up (95% CI: 5.80–6.95) emerged for the group of nonresponders
(p > 0.05), Figure 3 shows that nine (of 16) had an improvement in average pain that was smaller than 50%. Four
individuals encountered no change in their average pain and three individuals reported increases in average pain
between baseline and follow-up. Indeed, although average pain decreased (between baseline and follow-up) for
nonresponders (95% CI: 1.42–0.17), a significantly larger decrease was observed in the group of responders (95%
CI: -6.96 to -4.65; p < 0.001). This, therefore suggests that even in the group of nonresponders, the majority of
individuals were still doing well at follow-up with their BurstDR system.

BurstDR revisions, explantations & complications

Surgical revisions occurred in five (of 29) individuals (mean age ±1 SEM: 49.40 ± 4.40 years, n = 4 females;
no surgical revision mean age ±1 SEM: 48.46 ± 2.33 years, n = 12 females). This resulted in a revision rate of
around 17%. This included three patients who had one revision and two who had two revisions (mean number of
revisions ±1 SEM: 1.40 ± 2.45). Interestingly, two revisions were undertaken on a patient who reported increases
in average pain between baseline and follow-up. No patient had more than two revisions. As noted above, three
patients (of 32) had a full BurstDR system explanted, resulting in an explant rate of around 9%.
As revisions and explantations tend to result from complications, we were interested in exploring the occurrence
of four complications in particular in this cohort: lead migration, lead fracture, infection and IPG site pain. As
shown in Table 4, revisions occurred due to three lead migrations, two lead fractures, one infection and two who
encountered pain at their IPG site. Explantations resulted from one infection, one who encountered insufficient pain
relief and one who encountered side effects such as changes in visual perception. These data therefore demonstrate

324 Pain Manag. (2020) 10(5) future science group

 BurstDR spinal cord stimulation in the treatment of chronic visceral pain Research Article

Table 4. Summary of complications associated with revisions and explantations. Data are
presented as the number of times the complication occurred in the cohort.
Complications prompting revisions (n) Lead migration 3
Lead fracture 2
Infection 1
IPG site pain 2
Other 3
Complications prompting explantation (n) Infection 1
Insufficient pain relief 1
Other: side effects 1
IPG: Implantable pulse generator.

that BurstDR in this sample of individuals was associated with low rates of revision and explantation and few
complications.

Discussion
For the first time, we have presented findings from a retrospective study in a Teaching Hospitals Trust that
examined the efficacy and safety of BurstDR SCS in a group of individuals with chronic visceral pain. Consistent
with prior research investigating the effects of SCS in visceral pain conditions, findings from the retrospective study
demonstrated that a specific type of SCS, BurstDR, significantly improved average pain, worst pain and HRQoL
in a group of individuals who had chronic visceral pain. Importantly, baseline average pain scores were significantly
correlated with change at follow-up, where higher average pain at baseline was associated with greater improvements
postimplant. This, therefore suggests that it may be possible to identify individuals who are likely to encounter
greater improvements with BurstDR based on initial pain, perhaps enhancing outcomes for patients and clinicians
in the longer term. Interestingly, baseline visual analog scale scores have been shown to be predictive of success
with a differential neural block [40]. This adds further support to undertaking larger clinical trials that explore the
validity of using a baseline parameter to identify individuals with chronic visceral pain who respond to BurstDR.
13 individuals responded to BurstDR (i.e., showed ≥50% improvement in average pain between baseline and
follow-up) resulting in a response rate of 45%. Responders showed a significant decrease in average pain at follow-up
and also had a significantly greater improvement in average pain compared with nonresponders. Interestingly, most
nonresponders encountered improvements in their average pain with these improvements being less than 50%.
This, therefore means that the majority of individuals who received a fully implanted BurstDR system experienced
pain relief (22 of 29) with a minority either encountering no alleviation in pain (n = 4) or increases in their
pain (n = 3). For the patients who experienced small improvements in their pain, they still wanted to use the
therapy as it decreased their overall pain and antineuropathic medications, increased their QoL and reduced their
acute admissions and GP attendance. Although data on medication consumption and hospital admissions and GP
attendances were not collected in the retrospective study, these data combined with an economic analysis in our
PANACEA study should help inform the degree of improvement in other key aspects.
Another crucial question for this area relates to whether pain scores and a QoL index are the correct outcome
measures for chronic visceral pain patients. This is a debate that has not much answers at present but would benefit
from further investigation. Clearly, findings from the retrospective study are positive and encouraging, suggesting
that BurstDR can have long-term benefits in terms of pain for most individuals with chronic visceral pain. Of
course, larger, randomized clinical trials that evaluate the longer term effects of BurstDR are needed in this chronic
pain cohort. Taking inspiration from the PANACEA trial, this research could also include comparing the effects
of BurstDR to conventional medical management in order to determine the strengths and weaknesses of BurstDR
over traditional treatments. In turn, this would also provide further information pertaining to the safety profile of
BurstDR in chronic visceral pain conditions.
In the retrospective study, revisions occurred in 17% of the sample and explants occurred in 9%. Revisions and
explantations usually result from complications, with infection, lead migration, headache and diarrhea being noted
complications in research investigating SCS in chronic visceral pain (see Table 1 for a summary). IPG site pain
following a full SCS implant is also not an uncommon complication, with rates varying between studies from
0.9 [41] to 12% [42] (see [43] for a summary). In the retrospective cohort there were only two infections, one which

future science group www.futuremedicine.com 325

Research Article Baranidharan, Bretherton, Kay, Marsh, Romanis & Roberts

resulted in a revision and the other which prompted an explantation. Lead migration and fractures also occurred
in this sample (n = 3 and n = 2, respectively), leading to revisions only. Finally, IPG site pain was reported in
two cases, perhaps due to postoperative pain following implantation of the BurstDR system. These data, therefore
demonstrate that BurstDR in chronic visceral pain conditions is safe and going forward, future research should
methodically report complications so that guidelines can be updated to inform best practice and improve outcomes
for patients.

Study limitations
Due to the retrospective nature of the study, there will have been less control over potential covariates and
confounders compared with prospective clinical trials. As a result, some influential factors may have gone un-
reported in the current study and therefore warrant investigation in future research. This could include evaluating
the neuropathic element of chronic visceral pain conditions via validated neuropathic pain questionnaires, such as
the self-report leeds assessment of neuropathic symptoms and signs pain scale (S-LANSS) or douleur neuropathique
4 (DN4), and the occurrence of less well-documented complications that have been associated with SCS, such
as autonomic symptoms [32]. Although protocols were in place to guide the pain team during patient visits, the
reporting of some complications was not formalized. This, therefore renders it challenging to generate an accurate
rate of occurrence as well as the effects of complications on the well-being of individual patients. To overcome
this challenge, current practice and prospective clinical trials could systematically evaluate specific complications to
generate accurate rates and to explore how chronic visceral pain symptoms change with long-term use of BurstDR.
Despite the limitations associated with retrospective studies, findings can aid with producing the initial evidence
base needed in order to appropriately design and conduct large prospective clinical trials.

Conclusion & future perspective

In conclusion, chronic visceral pain can be a debilitating condition but with the development of new technologies,
including BurstDR, this patient cohort is presented with safer and more effective treatments. Early-stage clinical
trials have provided the initial evidence base for using SCS in chronic visceral pain conditions. Building on these
results, findings from a retrospective study investigating the efficacy and safety of BurstDR in individuals with
chronic visceral pain illustrated that the treatment significantly improved pain and HRQoL, with a response rate of
45% and minimal rates of revision, explantation and complications. A larger clinical trial investigating the effects
of BurstDR in a sample of individuals with chronic visceral pain secondary to chronic pancreatitis (PANACEA) is
ongoing. With further clinical research exploring the long-term effects of BurstDR with the inclusion of a control
arm, its efficacy and safety in difficult to treat chronic visceral pain conditions may be more fully established.

Author contributions
G Baranidharan conceived the study and led the team. With guidance from G Baranidharan, B Bretherton, T Kay, N Marsh,
C Romanis and B Roberts collected the data and B Bretherton performed the statistical analyses. B Bretherton wrote the manuscript
with support from G Baranidharan.

Financial & competing interests disclosure

G Baranidharan has consulting agreement with Nevro Corp, Medtronic, Boston Scientific, Nalu Medical and Abbott. G Baranidharan
had educational and research grants from Nevro Corp, Abbott and Boston Scientific. G Baranidharan has stock options with Nalu
Medical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined
in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human
subjects, informed consent has been obtained from the participants involved.

References
Papers of special note have been highlighted as: • of interest

326 Pain Manag. (2020) 10(5) future science group

 BurstDR spinal cord stimulation in the treatment of chronic visceral pain Research Article

Summary points
• Visceral pain arises following damage to internal organs and is characterized by constant background pain with
acute exacerbations requiring hospitalization. Presentations can be highly complex leading to challenges in
treatment.
• There is an urgent need to develop and identify new therapies that are safer and more effective than
conventional treatments. Spinal cord stimulation (SCS) holds promise.
• BurstDRTM (Abbott, TX, USA) is a type of SCS but unlike traditional systems, does not rely on paresthesia to mask
the pain and delivers groups of pulses separated by short pulse-free periods.
• A retrospective study on individuals with chronic visceral pain, who received BurstDR between 2013 and March
2020 in the Leeds Teaching Hospitals NHS Trust (n = 29) showed that pain and health-related quality of life
improved following BurstDR treatment.
• Baseline average pain significantly correlated with change at follow-up where higher initial average pain was
correlated with greater improvements at post-op.
• Although 45% of the sample responded to BurstDR (i.e., showed ≥50% improvement in average pain), around
76% showed decrease in pain at follow-up.
• BurstDR was safe: rates of revision, explantation and complications were low.
• Findings from prior work and those from the retrospective study illustrate that SCS (including BurstDR) is
effective and safe in chronic visceral pain conditions.
• It may be possible to identify potential responders to BurstDR from baseline pain scores, this warrants further
investigation.
• Larger clinical trials exploring the longer term effects of BurstDR (and SCS more widely) should be undertaken.

1. Baranidharan G, Simpson KH, Dhandapani K. Spinal cord stimulation for visceral pain – a novel approach. Neuromodulation 17(8),
753–758 (2014).
• Investigates the effects of ventral column spinal cord stimulation (SCS) in individuals with visceral neuropathic pain.
2. Penston JG, Pounder RE. A survey of dyspepsia in Great Britain. Aliment. Pharmacol. Ther. 10(1), 83–89 (1996).
3. Collett B. Visceral pain: the importance of pain management services. Br. J. Pain 7(1), 6–7 (2013).
4. Wallander MA, Johansson S, Ruigómez A, Garcı́a Rodrı́guez LA, Jones R. Dyspepsia in general practice: incidence, risk factors,
comorbidity and mortality. Fam. Pract. 24(5), 403–411 (2007).
5. Kay L, Jørgensen T, Jensen KH. The epidemiology of irritable bowel syndrome in a random population: prevalence, incidence, natural
history and risk factors. J. Intern. Med. 236(1), 23–30 (1994).
6. Wesselmann U, Baranowski AP, Börjesson M et al. Emerging therapies and novel approaches to visceral pain. Drug Discov. Today Ther.
Strateg. 6(3), 89–95 (2009).
• Provides an overview of the epidemiology, clinical, mechanistic and therapeutic aspects of visceral pain conditions.
7. Bosscher H. Blockade of the superior hypogastric plexus block for visceral pelvic pain. Pain Pract. 1(2), 162–170 (2001).
8. Petersohn JD. Sympathetic neural blockade. In: Pain Procedures in Clinical Practice (3rd Edition). Lennard TA, Walkowski S, Singla
AK, Vivian DG (Eds). Elsevier Health Sciences, PA, USA, 507–519 (2011).
9. Kapural L, Cywinski JB, Sparks DA. Spinal cord stimulation for visceral pain from chronic pancreatitis. Neuromodulation 14(5),
423–427 (2011).
10. Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord
stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 15(3), 347–354
(2014).
11. Salmon J. High-frequency spinal cord stimulation at 10 kHz for widespread pain: a retrospective survey of outcomes from combined
cervical and thoracic electrode placements. Postgrad. Med. 131(3), 230–238 (2019).
12. Gill JS, Asgerally A, Simopoulos TT. High-frequency spinal cord stimulation at 10 kHz for the treatment of complex regional pain
syndrome: a case series of patients with or without previous spinal cord stimulator implantation. Pain Pract. 19(3), 289–294 (2019).
13. Slangen R, Schaper NC, Faber CG et al. Spinal cord stimulation and pain relief in painful diabetic peripheral neuropathy: a prospective
two-center randomized controlled trial. Diabetes Care 37(11), 3016–3024 (2014).
14. De Ridder D, Vanneste S, van der Loo E, Plazier M, Menovsky T, Van de Heyning P. Burst stimulation of the auditory cortex: a new
form of neurostimulation for noise-like tinnitus suppression. J. Neurosurg. 112(6), 1289–1294 (2010).
15. De Ridder D, van der Loo E, Van der Kelen K, Menovsky T, van de Heyning P, Moller A. Theta, alpha and beta burst transcranial
magnetic stimulation: brain modulation in tinnitus. Int. J. Med. Sci., 4(5), 237–241 (2007).
16. Chakravarthy K, Fishman MA, Zuidema X, Hunter CW, Levy R. Mechanism of action in burst spinal cord stimulation: review and
recent advances. Pain Med. 20(Suppl. 1), S13–S22 (2019).

future science group www.futuremedicine.com 327

Research Article Baranidharan, Bretherton, Kay, Marsh, Romanis & Roberts

• Provides an overview of the potential mechanisms of action of BurstDR.

17. Kirketeig T, Schultheis C, Zuidema X, Hunter CW, Deer T. Burst spinal cord stimulation: a clinical review. Pain Med. 20(Suppl. 1),
S31–S40 (2019).
• Reviews clinical evidence of BurstDR in treating chronic pain.
18. De Ridder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. World Neurosurg.
80(5), 642–649 (2013).
19. De Ridder D, Lenders MW, De Vos CC et al. A 2-center comparative study on tonic versus burst spinal cord stimulation. Clin. J. Pain
31(5), 433–437 (2015).
20. Kinfe TM, Pintea B, Link C et al. High frequency (10kHz) or burst spinal cord stimulation in failed back surgery syndrome patients
with predominant back pain: preliminary data from a prospective observational study. Neuromodulation 19(3), 268–275 (2016).
21. Kinfe TM, Muhammad S, Link C, Roeske S, Chaudhry SR, Yearwood TL. Burst spinal cord stimulation increases peripheral
antineuroinflammatory interleukin 10 levels in failed back surgery syndrome patients with predominant back pain. Neuromodulation
20(4), 322–330 (2017).
22. Muhammad S, Roeske S, Chaudhry SR, Kinfe TM. Burst or high-frequency (10 kHz) spinal cord stimulation in failed back surgery
syndrome patients with predominant back pain: one year comparative data. Neuromodulation 20(7), 661–667 (2017).
23. Deer T, Slavin KV, Amirdelfan K et al. Success using neuromodulation with BURST (SUNBURST) study: results from a prospective,
randomized controlled trial using a novel burst waveform. Neuromodulation 21(1), 56–66 (2018).
24. de Vos CC, Bom MJ, Vanneste S, Lenders MW, De Ridder D. Burst spinal cord stimulation evaluated in patients with failed back
surgery syndrome and painful diabetic neuropathy. Neuromodulation 17(2), 152–159 (2014).
25. Kriek N, Groeneweg JG, Stronks DL, De Ridder D, Huygen FJPM. Preferred frequencies and waveforms for spinal cord stimulation in
patients with complex regional pain syndrome: a multicentre, double-blind, randomized and placebo-controlled crossover trial. Eur. J.
Pain 21(3), 507–519 (2017).
26. Vesper J, Slotty P, Schu S et al. Burst SCS microdosing is as efficacious as standard burst SCS in treating chronic back and leg pain:
results from a randomized controlled trial. Neuromodulation 22(2), 190–193 (2019).
27. Ceballos A, Cabezudo L, Bovaira M, Fenollosa P, Moro B. Spinal cord stimulation: a possible therapeutic alternative for chronic
mesenteric ischaemia. Pain 87(1), 99–101 (2000).
28. Jackson M, Simpson KH. Spinal cord stimulation in a patient with persistent oesophageal pain. Pain 112(3), 406–408 (2004).
29. Kapur S, Mutagi H, Raphael J. Spinal cord stimulation for relief of abdominal pain in two patients with familial Mediterranean fever. Br.
J. Anaesth. 97(6), 866–868 (2006).
30. Kapural L, Narouze SN, Janicki TI, Mekhail N. Spinal cord stimulation is an effective treatment for the chronic intractable visceral
pelvic pain. Pain Med. 7(5), 440–443 (2006).
31. Kapural L, Nagem H, Tlucek H, Sessler DI. Spinal cord stimulation for chronic visceral abdominal pain. Pain Med. 11(3), 347–355
(2010).
• Investigates the effects of SCS in individuals with visceral abdominal pain.
32. Kapural L, Deer T, Yakovlev A et al. Technical aspects of spinal cord stimulation for managing chronic visceral abdominal pain: the
results from the national survey. Pain Med. 11(5), 685–691 (2010).
• Presents the results of a survey exploring physician SCS practices for managing severe abdominal pain.
33. Kapural L, Cywinski JB, Sparks DA. Spinal cord stimulation for visceral pain from chronic pancreatitis. Neuromodulation 14(5),
423–427 (2011).
34. Kapural L, Rakic M. Spinal cord stimulation for chronic visceral pain secondary to chronic non-alcoholic pancreatitis. J. Clin.
Gastroenterol. 42(6), 750–751 (2008).
35. Khan YN, Raza SS, Khan EA. Application of spinal cord stimulation for the treatment of abdominal visceral pain syndromes.
Neuromodulation 8(1), 14–27 (2005).
36. Kim JK, Hong SH, Kim MH, Lee JK. Spinal cord stimulation for intractable visceral pain due to chronic pancreatitis. J. Korean
Neurosurg. Soc. 46(2), 165–167 (2009).
37. Krames E, Mousad DG. Spinal cord stimulation reverses pain and diarrheal episodes of irritable bowel syndrome: a case report.
Neuromodulation 7(2), 82–88 (2004).
38. Tiede JM, Ghazi SM, Lamer TJ, Obray JB. The use of spinal cord stimulation in refractory abdominal visceral pain: case reports and
literature review. Pain Pract. 6(3), 197–202 (2006).
39. Johnson CD, Hosking S. National statistics for diet, alcohol consumption, and chronic pancreatitis in England and Wales, 1960–1988.
Gut 32(11), 1401–1405 (1991).
40. Rizk MK, Tolba R, Kapura L et al. Differential epidural block predicts the success of visceral block in patients with chronic visceral
abdominal pain. Pain Pract. 12(8), 595–601 (2012).

328 Pain Manag. (2020) 10(5) future science group

 BurstDR spinal cord stimulation in the treatment of chronic visceral pain Research Article

41. Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. J. Neurosurg.
Spine 100(3), 254–267 (2004).
42. Kumar K, Taylor RS, Jacques L et al. The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the
prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation. Neurosurgery 63(4), 762–770 (2008).
43. Eldabe S, Buchser E, Duarte RV. Complications of spinal cord stimulation and peripheral nerve stimulation techniques: a review of the
literature. Pain Med. 17(2), 325–336 (2016).
• Presents an overview of complications that have been reported in patients treated with SCS and peripheral nerve stimulation.

future science group www.futuremedicine.com 329