Analysis of Somatosensory Profiles Using Quantitative Sensory Testing During Tonic and BurstDR Stimulation for the Treatment of Chronic Pain.

BACKGROUND: In the presence of neuropathic pain, other sensory qualities, such as touch or pressure, which are a sign of nerve damage, are almost always affected. However, it is unclear to which extent spinal cord stimulation (SCS) influences these simultaneously damaged sensory pathways or possibly contributes to their regeneration. OBJECTIVES: The aim of this study was to investigate the effects and possible differences of tonic and BurstDR (Abbott, Austin, TX) SCS on somatosensory profiles of patients with chronic neuropathic pain, using quantitative sensory testing (QST). STUDY DESIGN: A randomized, single-blinded, single-center study. SETTING: University medical center. METHODS: After a washout phase of 4 hours and having done the basic QST measurement, either tonic or BurstDR stimulation was performed for 30 minutes in a randomized fashion. Then, the second measurement was taken. The third measurement followed after using the remaining stimulation mode for 30 minutes. Mean values of all QST parameters were calculated and compared. We also computed Z-values using standard data. RESULTS: We examined 14 patients (9 women, 5 men, mean age 58.4 years) with previously implanted SCS systems for chronic neuropathic pain, using QST (7 tests, 13 parameters).The QST raw data showed a statistically significant improved vibration sensation (A-Beta) (P = 0.019) and lower mechanical pain threshold (A-Delta) (P = 0,031) when testing BurstDR in comparison to tonic SCS. We found a significant improvement in the vibration sensation and also A-Beta fiber function during BurstDR when we used the Z-value analysis (P = 0.023). With regard to Z-values, BurstDR seemed to be superior regarding the normalization tendency of the A-Delta fiber function in the mechanical pain threshold (P = 0.082), and tonic SCS seemed superior regarding heat detection threshold (C) and cold pain threshold (C and A-Delta) (P = 0.093). LIMITATIONS: The study is limited by its small number of cases. CONCLUSIONS: In this study, it could be shown that, in some QST parameters and tested fiber functions, normalization tendencies were recognizable by using BurstDR or tonic SCS. However, BurstDR SCS seemed to be superior to tonic stimulation in this regard.

Comparison of the Interference Effects on Somatosensory Evoked Potential from Tonic, Burst, and High-dose Spinal Cord Stimulations.

Spinal cord stimulations have been used widely to treat intractable neuropathic pain. The conventional spinal cord stimulation paradigm, the "tonic" type, suppresses excessive activation of wide dynamic range neurons in the dorsal horn via the collateral branch from the dorsal column. Therefore, preserved dorsal column function is an important prerequisite for tonic spinal cord stimulations. A tonic spinal cord stimulation requires eliciting paresthesia in the painful area due to stimulation of the dorsal column and dorsal root. Recent spinal cord stimulation paradigms, including burst and high-dose, are set below the paresthesia threshold and are proposed to have different pain reduction mechanisms. We conducted an interference study of these different stimulation paradigms on the somatosensory evoked potential (SEP) to investigate differences in the sites of action between tonic and new spinal cord stimulations. We recorded posterior tibial nerve-stimulated SEP in seven patients with neuropathic pain during tonic, burst, and high-dose stimulations. The total electrical energy delivered was calculated during SEP-spinal cord stimulation interference studies. High-dose stimulations could not reduce the SEP amplitude despite higher energy delivery than tonic stimulation. Burst stimulation with an energy similar to the tonic stimulation could not reduce SEP amplitude as tonic stimulation. The study results suggested different sites of action and effects on the spinal cord between the conventional tonic and burst or high-dose spinal cord stimulations.

Analgesic Effects of Tonic and Burst Dorsal Root Ganglion Stimulation in Rats With Painful Tibial Nerve Injury.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is effective in treating chronic pain. While burst stimulation has been proven to enhance the therapeutic efficacy in spinal cord stimulation, currently only a tonic stimulation waveform is clinically used in DRG stimulation. We hypothesized that burst DRG stimulation might also produce analgesic effect in a preclinical neuropathic pain model. We evaluated both the therapeutic effects of burst DRG stimulation and the possible effects of DRG stimulation upon inflammation within the DRG in a preclinical neuropathic pain model. MATERIALS AND METHODS: Rats received either a painful tibial nerve injury or sham surgery. Analgesic effects of DRG stimulation were evaluated by testing a battery of evoked pain-related behaviors as well as measuring the positive affective state associated with relief of spontaneous pain using conditioned place preference. Histological evidence for neuronal trauma or neuroinflammation was evaluated. RESULTS: All of the waveforms tested (20 Hz-tonic, 20 Hz-burst, and 40 Hz-burst) have similar analgesic effects in sensory tests and conditioned place preference. Long-term DRG stimulation for two weeks does not change DRG expression of markers for nerve injury and neuroinflammation. CONCLUSIONS: DRG stimulation using burst waveform might be also suitable for treating neuropathic pain.

Dependency on sex and stimulus quality of nociceptive behavior in a conscious visceral pain rat model.

Visceral pain may be influenced by many factors. The aim of this study was to analyze the impact of sex and quality of intracolonic mechanical stimulus on the behavioral manifestations of visceral pain in a preclinical model. Male and female young adult Wistar rats were sedated, and a 5 cm long latex balloon was inserted into the colon. Sedation was reverted and behavior was recorded. The pressure of the intracolonic balloon was gradually increased using a sphygmomanometer. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation. Two different types of stimulation were used: tonic and phasic. Phasic stimulation consisted of repeating several times (3x) the same short stimulus (20 s) within a 5 min interval allowing a 1 min break between individual stimuli. For tonic stimulation the stimulus was maintained throughout the whole 5 min interval. Both phasic and tonic stimulation produced a pressure-dependent increase of abdominal contractions. The abdominal response was more intense under phasic than under tonic stimulation, but with differences depending on the sex of the animals: females exhibited more contractions than males and of similar duration at all pressures, whereas duration of contractions pressure-dependently increased in males. The duration of tonically stimulated contractions was lower and not sex- or pressure-dependent. In the rat, responses to colonic distension depend on the quality of the stimulus, which also produces sex-dependent differences that must be taken into account in the development of models of pathology and visceral pain treatments.

Neuromodulation With Burst and Tonic Stimulation Decreases Opioid Consumption: A Post Hoc Analysis of the Success Using Neuromodulation With BURST (SUNBURST) Randomized Controlled Trial.

OBJECTIVE: The SUNBURST study was a prospective, multicenter, randomized crossover trial of a single device delivering burst and tonic spinal cord stimulation (SCS) for chronic trunk and/or limb pain. We performed a post hoc analysis of opioid consumption at baseline and after device implantation. MATERIALS AND METHODS: After implantation, 100 patients were randomized to one mode (tonic or burst) for 12 weeks, and the other mode for the subsequent 12 weeks. After the crossover period (24 weeks), patients chose their preferred mode and were assessed for one year. We analyzed 69 patients who took opioid medication at baseline. The primary endpoint was opioid consumption in morphine milligram equivalents (MMEs) at baseline and 12 months postimplantation. Subgroup analysis included opioid consumption based on Center for Disease Control markers (<50, 50-90, 90-120, >120 MME/day) and stimulation mode preference. RESULTS: Opioid consumption at 12 months was lower compared to baseline (53.94 vs. 79.19 MME, MD -25.25, 95% CI -43.77 to 6.73, p = 0.008). By 12 months, 11 of 69 patients (15.9%) discontinued all opioid (p = 0.001). Based on CDC dose markers, the proportion of patients taking >120 MME/day decreased by 61.7% at 12 months postintervention compared to baseline (p = 0.043). Forty-five of 69 patients (65.2%) preferred burst SCS while 15 of 69 patients (21.7%) preferred tonic SCS (p < 0.001). CONCLUSION: A device delivering tonic and burst SCS was associated with decreased opioid consumption after 12 months in patients with chronic trunk and/or limb pain. The proportion of patients reporting the highest opioid intake (>120 MME/day) decreased to a lower CDC dose category by 61.7%, carrying important implications for those at highest risk for opioid-related substance use disorder, overdose, and death.

High Cervical Spinal Cord Stimulation: A One Year Follow-Up Study on Motor and Non-Motor Functions in Parkinson's Disease.

BACKGROUND: The present study investigated the effectiveness of stimulation applied at cervical levels on pain and Parkinson's disease (PD) symptoms using either tonic or burst stimulation mode. METHODS: Tonic high cervical spinal cord stimulation (T-HCSCS) was applied on six PD patients suffering from low back pain and failed back surgery syndrome, while burst HCSCS (B-HCSCS) was applied in twelve PD patients to treat primarily motor deficits. Stimulation was applied percutaneously with quadripolar or octapolar electrodes. Clinical evaluation was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H&Y) scale. Pain was evaluated by a visual analog scale. Evaluations of gait and of performance in a cognitive motor task were performed in some patients subjected to B-HCSCS. One patient who also suffered from severe autonomic cardiovascular dysfunction was investigated to evaluate the effectiveness of B-HCSCS on autonomic functions. RESULTS: B-HCSCS was more effective and had more consistent effects than T-HCSCS in reducing pain. In addition, B-HCSCS improved UPDRS scores, including motor sub-items and tremor and H&Y score. Motor benefits appeared quickly after the beginning of B-HCSCS, in contrast to long latency improvements induced by T-HCSCS. A slight decrease of effectiveness was observed 12 months after implantation. B-HCSCS also improved gait and ability of patients to correctly perform a cognitive-motor task requiring inhibition of a prepared movement. Finally, B-HCSCS ameliorated autonomic control in the investigated patient. CONCLUSIONS: The results support a better usefulness of B-HCSCS compared to T-HCSCS in controlling pain and specific aspects of PD motor and non-motor deficits for at least one year.

Burst and high frequency stimulation: underlying mechanism of action.

INTRODUCTION: Paresthesia-free spinal cord stimulation (SCS) techniques, such as burst and high-frequency (HF) SCS, have been developed and demonstrated to be successful for treating chronic pain, albeit via different mechanisms of action. The goal of this review is to discuss the mechanisms of action for pain suppression at both the cellular and systems levels for burst and HF SCS. In addition, we also discuss the neuromodulation devices that mimic these paradigms. AREAS COVERED: The authors performed a literature review to unravel the mechanisms of action for burst and HF SCS coupled with booklets and user manuals from neuromodulation companies to understand the programmable parameters and operating ranges. Burst SCS modulates the medial pathway to suppress pain. On cellular level, burst SCS is independent on activation of γ-aminobutyric acid (GABA) receptors to inhibit neuronal firing. HF SCS blocks large-diameter fibers from producing action potentials with little influence on smaller fibers, increasing pain suppression as frequency increases. EXPERT COMMENTARY: The neuromodulation industry is in a phase of intense innovation characterized by adaptive stimulation to improve patients' experience and experiment with alternative frequencies and novel stimulation targets.

Success Using Neuromodulation With BURST (SUNBURST) Study: Results From a Prospective, Randomized Controlled Trial Using a Novel Burst Waveform.

OBJECTIVE: The purpose of the multicenter, randomized, unblinded, crossover Success Using Neuromodulation with BURST (SUNBURST) study was to determine the safety and efficacy of a device delivering both traditional tonic stimulation and burst stimulation to patients with chronic pain of the trunk and/or limbs. METHODS: Following a successful tonic trial, 100 subjects were randomized to receive one stimulation mode for the first 12 weeks, and then the other stimulation mode for the next 12 weeks. The primary endpoint assessed the noninferiority of the within-subject difference between tonic and burst for the mean daily overall VAS score. An intention-to-treat analysis was conducted using data at the 12- and 24-week visits. Subjects then used the stimulation mode of their choice and were followed for one year. Descriptive statistics were used analyze additional endpoints and to characterize the safety profile of the device. RESULTS: The SUNBURST study demonstrated that burst stimulation is noninferior to tonic stimulation (p < 0.001). Superiority of burst was also achieved (p < 0.017). Significantly more subjects (70.8%) preferred burst stimulation over tonic stimulation (p < 0.001). Preference was sustained through one year: 68.2% of subjects preferred burst stimulation, 23.9% of subjects preferred tonic, and 8.0% of subjects had no preference. No unanticipated adverse events were reported and the safety profile was similar to other spinal cord stimulation studies. CONCLUSIONS: The SUNBURST study demonstrated that burst spinal cord stimulation is safe and effective. Burst stimulation was not only noninferior but also superior to tonic stimulation for the treatment of chronic pain. A multimodal stimulation device has advantages.

Tonic and burst spinal cord stimulation waveforms for the treatment of chronic, intractable pain: study protocol for a randomized controlled trial.

BACKGROUND: Burst stimulation is a novel form of neurostimulation for the treatment of chronic pain which has demonstrated promise in small uncontrolled studies, but has not yet gained approval for use in the U.S. We report the study methods for an ongoing multicenter, randomized, controlled, cross-over study designed to gain United States Food and Drug Administration (FDA) approval for burst stimulation. METHODS: Participants who are candidates for a currently approved neurostimulation device were enrolled and screened. Participants who fail a tonic trial evaluation, have significant depressive symptoms, or evidence lack of compliance with study procedures by failing to complete 7 days of a Pain Diary are excluded. Participants receiving a permanent implant are randomized to receive: (1) 12 weeks of tonic followed by 12 weeks of burst stimulation or (2) 12 weeks of burst stimulation followed by 12 weeks of tonic stimulation. Assessments occur at 6, 12, 18, and 24 weeks. After 24 weeks, participants choose their preferred therapy and are assessed every 6 months for up to 2 years. All patients had the device leads inserted at the site of a successful tonic stimulation trial. Assessments include: a Pain Diary using a Visual Analog Scale (VAS) for overall, trunk, and limb pain, the Beck Depression Inventory, the Pain Catastrophizing Scale, the Oswestry Disability Index, paresthesia, satisfaction, and therapy preference. Reported adverse events are collected throughout the study. The primary endpoint is the noninferiority of burst stimulation compared to tonic measured by the within-subject difference in the mean overall VAS score at the end of each 12-week stimulation period. DISCUSSION: This trial represents the largest controlled trial of burst stimulation to date, and is expected to yield important information regarding the safety and efficacy of burst stimulation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02011893 . Registered on 10 December 2013.

Effect of Burst Stimulation Evaluated in Patients Familiar With Spinal Cord Stimulation.

OBJECTIVE: Spinal cord stimulation (SCS) is used for treating intractable neuropathic pain. It has been suggested that burst SCS (five pulses at 500 Hz, delivered 40 times per second) suppresses neuropathic pain at least as well as conventional tonic SCS, but without evoking paraesthesia. The efficacy of paraesthesia-free high and low amplitude burst SCS for the treatment of neuropathic pain in patients who are already familiar with tonic SCS was evaluated. MATERIALS AND METHODS: Forty patients receiving conventional (30-120 Hz) tonic SCS for at least six months were included. All patients received high and low amplitude burst SCS, for a two-week period in a double blind randomized crossover design, with a two-week period of tonic stimulation in between. The average visual analogue scale (VAS) scores for pain during the last three days of each stimulation period were evaluated as well as quality of life (QoL) scores, and patient's preferences. RESULTS: Average VAS score for pain were lower during high (40, p = 0.013) and low amplitude burst stimulation (42, p = 0.053) compared with tonic stimulation (52). QoL scores did not differ significantly. At the individual level 58% of the patients experienced significant additional pain reduction (>30% decrease in VAS for pain) during high and/or low amplitude burst stimulation. Eleven patients preferred tonic stimulation, fifteen high, and fourteen low amplitude burst stimulation. CONCLUSION: Burst stimulation is in general more effective than tonic stimulation. Individual patients can highly benefit from burst stimulation; however, the therapeutic range of burst stimulation amplitudes requires individual assessment.

Burst Spinal Cord Stimulation in a Patient with Complex Regional Pain Syndrome: A 2-year Follow-Up.

UNLABELLED: Spinal cord stimulation (SCS) is an effective therapy to treat most patients with complex regional pain syndrome (CRPS); however, the effect is not always maintained over time. We present a case report of a patient successfully treated with burst SCS after a diminishing effect of conventional tonic stimulation. Burst stimulation is a novel method of SCS consisting of delivering 5 spikes at 500 Hz, 40 times/s (pulse width 1 mseconds). The current output is set to a subthreshold level for paresthesia in the supine position. REPORT OF A CASE: A 65-year-old woman with CRPS in the left upper extremity experienced a diminishing effect of conventional tonic SCS over time, resulting in an increase of pain with a mean Numerical Rating Score (NRS) of 8. After treatment with burst SCS, the NRS declined to 2 and remained at that level for 2 years. An intermediate/brief period, due to increased CRPS activity, resulted in a higher pain score, which was successfully managed by increasing the burst stimulation to a higher level of subthreshold stimulation. DISCUSSION: In this patient with CRPS, burst SCS was successful in reducing pain scores that could no longer be achieved with conventional tonic stimulation. It appears that pain reduction with burst SCS can be sustained for a relatively long period of time.

Improved Pain Relief With Burst Spinal Cord Stimulation for Two Weeks in Patients Using Tonic Stimulation: Results From a Small Clinical Study.

OBJECTIVES: Conventional spinal cord stimulation (SCS) delivers a tonic waveform with consistent stream of pulses; burst delivers groups of pulses separated by short pulse-free periods. The current study compared the short-term safety and efficacy of burst with tonic stimulation in subjects already receiving SCS. MATERIALS AND METHODS: At 4 IRB-approved sites, 22 subjects previously implanted with an SCS device for intractable, chronic pain gave informed consent and received burst stimulation for 14 days. Subjects reported average daily Visual Analog Scale (VAS) for overall, trunk, and limb pain using tonic stimulation and after 7 and 14 days of burst stimulation. Thoughts about pain were assessed using the Pain Catastrophizing Scale. Areas of paresthesia were assessed during tonic and burst stimulation using body maps. Assessment of patient satisfaction and preferred stimulation occurred after 14 days of burst. RESULTS: Average daily overall VAS reduced 46% from a mean of 53.5 (±20.2) mm during tonic SCS to 28.5 (±18.1) mm during burst (p < 0.001); trunk and limb VAS scores were also reduced by 33% and 51%, respectively. During burst, 16 subjects (73%) reported no paresthesia, 5 (23%) reported a reduction, and 1 (4%) reported increased paresthesia. After 14 days, 21 subjects (95%) reported being very satisfied or satisfied with burst. Burst was preferred by 20 subjects (91%), tonic by 1 (5%), and 1 (5%) reported no preference. Better pain relief was the most common reason cited for preference. CONCLUSIONS: A majority of subjects reported improved pain relief using burst compared with tonic stimulation. Most subjects experienced less paresthesia during burst and preferred burst citing better pain relief.