Frequency-Dependent Neural Modulation of Dorsal Horn Neurons by Kilohertz Spinal Cord Stimulation in Rats.

Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In this study, using a novel preparation, we investigated the impact of varying kilohertz frequency SCS on dorsal horn neuron activation. Employing calcium imaging on isolated spinal cord slices, we found that extracellular electric fields at kilohertz frequencies (1, 3, 5, 8, and 10 kHz) induce distinct patterns of activation in dorsal horn neurons. Notably, as the frequency of extracellular electric fields increased, there was a clear and significant monotonic escalation in neuronal activity. This phenomenon was observed not only in superficial dorsal horn neurons, but also in those located deeper within the dorsal horn. Our study demonstrates the unique patterns of dorsal horn neuron activation in response to varying kilohertz frequencies of extracellular electric fields, and we contribute to a deeper understanding of how kHF-SCS induces paresthesia-free pain relief. Furthermore, our study highlights the potential for kHF-SCS to modulate sensory information processing within spinal pain circuits. These insights pave the way for future research aimed at optimizing kHF-SCS parameters and refining its therapeutic applications in the clinical management of chronic pain.

Improvement in Protective Sensation: Clinical Evidence From a Randomized Controlled Trial for Treatment of Painful Diabetic Neuropathy With 10 kHz Spinal Cord Stimulation.

BACKGROUND: Painful diabetic neuropathy (PDN) can result in the loss of protective sensation, in which people are at twice the likelihood of foot ulceration and three times the risk of lower extremity amputation. Here, we evaluated the long-term effects of high-frequency (10 kHz) paresthesia-independent spinal cord stimulation (SCS) on protective sensation in the feet and the associated risk of foot ulceration for individuals with PDN. METHODS: The SENZA-PDN clinical study was a randomized, controlled trial in which 216 participants with PDN were randomized to receive either conventional medical management (CMM) alone or 10 kHz SCS plus CMM, with optional treatment crossover after 6 months. At study visits (baseline through 24 months), 10-g monofilament sensory assessments were conducted at 10 locations per foot. Two published methods were used to evaluate protective sensation via classifying risk of foot ulceration. RESULTS: Participants in the 10 kHz SCS group reported increased numbers of sensate locations as compared to CMM alone (P < .001) and to preimplantation (P < .01) and were significantly more likely to be at low risk of foot ulceration using both classification methods. The proportion of low-risk participants approximately doubled from preimplantation to 3 months postimplantation and remained stable through 24 months (P ≤ .01). CONCLUSIONS: Significant improvements were observed in protective sensation from preimplantation to 24 months postimplantation for the 10 kHz SCS group. With this unique, disease-modifying improvement in sensory function, 10 kHz SCS provides the potential to reduce ulceration, amputation, and other severe sequelae of PDN. TRIAL REGISTRATION: The SENZA-PDN study is registered on ClinicalTrials.gov with identifier NCT03228420.

Simultaneous 10 kHz and 40 Hz spinal cord stimulation increases dorsal horn inhibitory interneuron activity.

Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Low-intensity, paresthesia-free, 10 kHz SCS has demonstrated statistically- and clinically-superior long-term pain relief compared to conventional SCS. 10 kHz SCS has been proposed to operate via selective activation of inhibitory interneurons in the superficial dorsal horn. In contrast, 40 Hz SCS is presumed to operate largely via dorsal column fiber activation. To determine if these mechanisms may be implemented synergistically, we examined the effect of each type of stimulation both independently and simultaneously on putatively inhibitory and putatively excitatory neurons in the superficial dorsal horn. When 10 kHz SCS was applied relatively caudally to the measured spinal segment, simultaneous with 40 Hz SCS applied relatively rostrally to that spinal segment, inhibitory interneurons demonstrated a median increase of 26 spikes/s compared to their baseline firing rates. Median firing rate increases of inhibitory interneurons were 8.7 and 5.1 spikes/s during 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally, respectively. By comparison, the median firing rate of excitatory interneurons increased by 4.1 spikes/s during simultaneous 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally. Median firing rate increases of excitatory interneurons were 13 and 0.8 spikes/s during 40 Hz SCS applied rostrally and 10 kHz SCS applied caudally, respectively. This suggests that simultaneously applying 10 kHz SCS caudally and 40 Hz SCS rostrally may provide greater pain relief than either type of SCS alone by increasing the firing rates of inhibitory interneurons, albeit with greater excitatory interneuron activation.

Low-Intensity 10 kHz Spinal Cord Stimulation Reduces Behavioral and Neural Hypersensitivity in a Rat Model of Painful Diabetic Neuropathy.

Background: Low-intensity 10 kHz spinal cord stimulation (SCS) has been shown to provide pain relief in patients with chronic pain resulting from diabetic peripheral neuropathy (DPN). However to date, there have been no studies of 10 kHz SCS in animal models of diabetes. We aimed to establish correlative data of the effects of this therapy on behavioral and electrophysiological measures in a DPN model. Methods: Twenty-five adult male Sprague-Dawley rats were injected once intraperitoneally with 60 mg/kg streptozotocin (STZ) to induce diabetes over a subsequent 4 w period, while 4 naïve control animals were not injected. After approximately 21 d, 12 of STZ-injected rats had mini epidural SCS leads implanted: 8 received continuous low intensity (~30% motor threshold) 10 kHz SCS, and 4 received sham SCS (0 mA) over 7 d. Behavioral assays (von Frey filament probe of hindpaw) were measured in 18 animals and in vivo dorsal horn electrophysiological studies (receptive field; response to afferent brush, von Frey probe, pinch) were performed in 17 animals. Results: Across behavioral assays of mechanical allodynia and electrophysiological assays of receptive field size and mechanosensitivity, diabetic animals stimulated with 10 kHz SCS showed statistically significant improvements compared to sham SCS. Conclusion: Low-intensity 10 kHz SCS produced several measures associated with a reduction of pain in diabetic rodent models that may help explain the clinical benefits of 10 kHz SCS in patients with painful diabetic neuropathy.

Pulse Dosing of 10-kHz Paresthesia-Independent Spinal Cord Stimulation Provides the Same Efficacy with Substantial Reduction of Device Recharge Time.

OBJECTIVE: This study was designed to assess whether using pulse dosing (PD) (regularly cycled intermittent stimulation) of high-frequency 10-kHz spinal cord stimulation (10-kHz SCS) can reduce device recharge time while maintaining efficacy in patients with chronic intractable back pain with or without leg pain. DESIGN: Prospective, multicenter, observational study. METHODS: Patients successfully using 10-kHz SCS at 100%ON (i.e., continuously with no PD) for >3 months were consecutively enrolled. After a 1-week baseline period of documenting their pain twice daily on a 0-10 numerical rating scale (NRS) using 100%ON of their "favorite" program, all subjects were reprogrammed to 14%PD for 10-14 days. If subjects preferred 14%PD to 100%ON, they were programmed to 3%PD; otherwise, they were programmed to 50%PD. Subjects used this next program for another 10-14 days. Subjects then entered a 3-month observational period during which they were requested to use but not limited to their most preferred %PD program. Toward the end of 3 months, subjects completed a 7-day NRS diary and indicated a final %PD program preference. Study endpoints included %PD preference, mean diary NRS by %PD, and daily minutes and patterns of charging. RESULTS: Of 31 subjects completing the study, 81% preferred less than 100%ON. Among the subjects, 39% preferred 3%PD, 32% preferred 14%PD, 10% preferred 50%PD, and 19% preferred 100%ON. Average daily charge durations were 8.3 ± 3.1 minutes for 3%PD, 13.9 ± 4.9 minutes for 14%PD, 26.2 ± 7.4 minutes for 50%PD, and 43.8 ± 10.9 minutes for 100%ON. Regression modeling suggested that pain relief was weighted as more than twice as influential as charging in preference for reduced %PD. CONCLUSIONS: This prospective study suggests that 10-kHz SCS therapy with PD may be successfully used in a large majority of 10-kHz SCS responders, maintaining efficacy while reducing device charging time by nearly two thirds.

Differential Modulation of Dorsal Horn Neurons by Various Spinal Cord Stimulation Strategies.

New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS. To determine if 10 kHz and burst SCS waveforms might have a similar mechanistic basis, we examined whether these SCS strategies at intensities ostensibly below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using an in vivo electrophysiological approach in rodents, we found that low-intensity 10 kHz SCS, but not burst SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief, whereas burst SCS likely operates via other mechanisms.

Low-intensity, Kilohertz Frequency Spinal Cord Stimulation Differently Affects Excitatory and Inhibitory Neurons in the Rodent Superficial Dorsal Horn.

Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Compared to traditional high-intensity, low-frequency (<100 Hz) SCS that is thought to produce paresthesia and pain relief by stimulating large myelinated fibers in the dorsal column (DC), low-intensity, high-frequency (10 kHz) SCS has demonstrated long-term pain relief without generation of paresthesia. To understand this paresthesia-free analgesic mechanism of 10 kHz SCS, we examined whether 10 kHz SCS at intensities below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using in vivo and ex vivo electrophysiological approaches, we found that low-intensity (sub-sensory threshold) 10 kHz SCS, but not 1 kHz or 5 kHz SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief.

Methodology for quantifying excitability of identified projection neurons in the dorsal horn of the spinal cord, specifically to study spinal cord stimulation paradigms.

BACKGROUND: Using in and ex vivo preparations, electrophysiological methods help understand the excitability of biological tissue, particularly neurons, by providing microsecond temporal resolution. However, for in vivo recordings, in the context of extracellular recordings, it is often unclear precisely which type of neuron the tip of the electrode is recording from. This is particularly true in the densely-populated central nervous system, such as the spinal cord dorsal horn at both superficial and deep levels. NEW METHOD: Here, we present a detailed protocol for the identification of superficial dorsal horn spinal cord neurons that receive peripheral input and project to the brain, using multiple surgical laminectomies and the careful placement of electrodes. Once a superficial projection unit was found, quantification to electrical peripheral stimulation was performed using a Matlab algorithm to form a template of projection neuron response to controlled C2 stimulation and accurately match this to the responses from peripheral stimulation. RESULTS: These superficial spinal projection neurons are normally activated by noxious peripheral stimuli, so we adopted a well-characterised wind-up protocol to obtain a neuronal excitability profile. Once achieved, this protocol allows for testing specific interventions, either pharmacological or neuromodulatory (e.g., spinal cord stimulation) to see how these affect the neuron's excitability. This preparation is robust and allows the accurate tracking of a projection neuron for over 3-h. COMPARISON WITH EXISTING METHOD(S): Currently, most existing methods record from dorsal horn neurons that are often profiled based on their excitability to different peripherally-applied sensory modalities. While this is well-established, it fails to discriminate between interneurons and projection neurons, which is important as these two populations signal via distinctly different neuronal networks. Using the approach detailed here will result in studies with improved mechanistic understanding of the signal integration and processing that occurs in the superficial dorsal horn. CONCLUSIONS: The refinements detailed in this protocol allow for more comprehensive studies to be carried out that will help understand spinal plasticity, in addition to many considerations for isolating the relevant neuronal population when performing in vivo electrophysiology.

Paresthesia-Independence: An Assessment of Technical Factors Related to 10 kHz Paresthesia-Free Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation (SCS) has been successfully used to treat chronic intractable pain for over 40 years. Successful clinical application of SCS is presumed to be generally dependent on maximizing paresthesia-pain overlap; critical to achieving this is positioning of the stimulation field at the physiologic midline. Recently, the necessity of paresthesia for achieving effective relief in SCS has been challenged by the introduction of 10 kHz paresthesia-free stimulation. In a large, prospective, randomized controlled pivotal trial, HF10 therapy was demonstrated to be statistically and clinically superior to paresthesia-based SCS in the treatment of severe chronic low back and leg pain. HF10 therapy, unlike traditional paresthesia-based SCS, requires no paresthesia to be experienced by the patient, nor does it require paresthesia mapping at any point during lead implant or post-operative programming. OBJECTIVES: To determine if pain relief was related to technical factors of paresthesia, we measured and analyzed the paresthesia responses of patients successfully using HF10 therapy. STUDY DESIGN: Prospective, multicenter, non-randomized, non-controlled interventional study. SETTING: Outpatient pain clinic at 10 centers across the US and Italy. METHODS: Patients with both back and leg pain already implanted with an HF10 therapy device for up to 24 months were included in this multicenter study. Patients provided pain scores prior to and after using HF10 therapy. Each patient's most efficacious HF10 therapy stimulation program was temporarily modified to a low frequency (LF; 60 Hz), wide pulse width (~470 mus), paresthesia-generating program. On a human body diagram, patients drew the locations of their chronic intractable pain and, with the modified program activated, all regions where they experienced LF paresthesia. Paresthesia and pain drawings were then analyzed to estimate the correlation of pain relief outcomes to overlap of pain by paresthesia, and the mediolateral distribution of paresthesia (as a surrogate of physiologic midline lead positioning). RESULTS: A total of 61 patients participated across 11 centers. Twenty-eight men and 33 women with a mean age of 56 ± 12 years of age participated in the study. The average duration of implantable pulse generator (IPG) implant was 19 ± 9 months. The average predominant pain score, as measured on a 0 - 10 visual analog scale (VAS), prior to HF10 therapy was 7.8 ± 1.3 and at time of testing was 2.5 ± 2.1, yielding an average pain relief of 70 ± 24%. For all patients, the mean paresthesia coverage of pain was 21 ± 28%, with 43% of patients having zero paresthesia coverage of pain. Analysis revealed no correlation between percentage of LF paresthesia overlap of predominant pain and HF10 therapy efficacy (P = 0.56). Exact mediolateral positioning of the stimulation electrodes was not found to be a statistically significant predictor of pain relief outcomes. LIMITATIONS: Non-randomized/non-controlled study design; short-term evaluation; certain technical factors not investigated. CONCLUSION: Both paresthesia concordance with pain and precise midline positioning of the stimulation contacts appear to be inconsequential technical factors for successful HF10 therapy application. These results suggest that HF10 therapy is not only paresthesia-free, but may be paresthesia-independent.

Spinal Cord Stimulation in Chronic Pain: Mode of Action.

STUDY DESIGN: Literature review. OBJECTIVE: A review of the literature that presents a perspective on mechanisms of actions behind spinal cord stimulation (SCS) therapy for chronic pain. SUMMARY OF BACKGROUND DATA: SCS is an effective therapeutic alternative for the treatment of intractable chronic pain. Its application has been mostly based on the gate control theory of pain. Computational models have been fundamental on the understanding of clinical observations and the design of therapies that provide optimal neuromodulation. Research has provided insight into the involvement of specific neurotransmitters that support segmental and supraspinal mechanisms of action. METHODS: A literature review was performed with emphasis on mechanisms of action for SCS including the effects of electrical fields on spinal cord structures based on computational models and preclinical and clinical explorations. RESULTS: This review provides background on the development of SCS, which has been driven around a paresthesia-based paradigm as a result of the gate control theory. A review of computational models emphasizes their importance on our current understanding of the mechanism of action and clinical optimization of therapy. Electrophysiology and molecular biology have provided a closer, yet narrow, view of the effect of SCS on neurotransmitters and their receptors, which have led to the formulation of segmental and supraspinal mechanisms. Literature supporting the involvement of glial cells in chronic pain and their characteristic response to electrical fields should motivate further investigation of mechanisms involving neuroglia. Finally, a review of recent results paresthesia-free strategies should encourage research on mechanisms of action. CONCLUSION: The mechanisms of SCS have been extensively studied and several consistent phenomena have emerged. The activation of A-beta fibers to induce paresthesia also involve neurotransmitter release via segmental and supraspinal pathways. Despite advancements, much remains to be understood, particularly as new stimulation strategies are developed. LEVEL OF EVIDENCE: N /A.

Predicted effects of pulse width programming in spinal cord stimulation: a mathematical modeling study.

To understand the theoretical effects of pulse width (PW) programming in spinal cord stimulation (SCS), we implemented a mathematical model of electrical fields and neural activation in SCS to gain insight into the effects of PW programming. The computational model was composed of a finite element model for structure and electrical properties, coupled with a nonlinear double-cable axon model to predict nerve excitation for different myelinated fiber sizes. Mathematical modeling suggested that mediolateral lead position may affect chronaxie and rheobase values, as well as predict greater activation of medial dorsal column fibers with increased PW. These modeling results were validated by a companion clinical study. Thus, variable PW programming in SCS appears to have theoretical value, demonstrated by the ability to increase and even 'steer' spatial selectivity of dorsal column fiber recruitment. It is concluded that the computational SCS model is a valuable tool to understand basic mechanisms of nerve fiber excitation modulated by stimulation parameters such as PW and electric fields.

Dorsal column steerability with dual parallel leads using dedicated power sources: a computational model.

In spinal cord stimulation (SCS), concordance of stimulation-induced paresthesia over painful body regions is a necessary condition for therapeutic efficacy. Since patient pain patterns can be unique, a common stimulation configuration is the placement of two leads in parallel in the dorsal epidural space. This construct provides flexibility in steering stimulation current mediolaterally over the dorsal column to achieve better pain-paresthesia overlap. Using a mathematical model with an accurate fiber diameter distribution, we studied the ability of dual parallel leads to steer stimulation between adjacent contacts on dual parallel leads using (1) a single source system, and (2) a multi-source system, with a dedicated current source for each contact. The volume conductor model of a low-thoracic spinal cord with epidurally-positioned dual parallel (2 mm separation) percutaneous leads was first created, and the electric field was calculated using ANSYS, a finite element modeling tool. The activating function for 10 um fibers was computed as the second difference of the extracellular potential along the nodes of Ranvier on the nerve fibers in the dorsal column. The volume of activation (VOA) and the central point of the VOA were computed using a predetermined threshold of the activating function. The model compared the field steering results with single source versus dedicated power source systems on dual 8-contact stimulation leads. The model predicted that the multi-source system can target more central points of stimulation on the dorsal column than a single source system (100 vs. 3) and the mean steering step for mediolateral steering is 0.02 mm for multi-source systems vs 1 mm for single source systems, a 50-fold improvement. The ability to center stimulation regions in the dorsal column with high resolution may allow for better optimization of paresthesia-pain overlap in patients.

Pulse width programming in spinal cord stimulation: a clinical study.

BACKGROUND: With advances in spinal cord stimulation (SCS) technology, particularly rechargeable implantable, patients are now being offered a wider range of parameters to treat their pain. In particular, pulse width (PW) programming ranges of rechargeable implantable pulse generators now match that of radiofrequency systems (with programmability up to 1000 microseconds. The intent of the present study was to investigate the effects of varying PW in SCS. OBJECTIVE: To understand the effects of PW programming in spinal cord stimulation (SCS). DESIGN: Single-center, prospective, randomized, single-blind evaluation of the technical and clinical outcomes of PW programming. SETTING: Acute, outpatient follow-up. METHODS: Subjects using fully-implanted SCS for > 3 months to treat chronic intractable low back and/or leg pain. Programming of a wide range (50-1000 microseconds) of programmed PW settings using each patient's otherwise unchanged 'walk-in' program. OUTCOME MEASURES: Paresthesia thresholds (perception, maximum comfortable, discomfort), paresthesia coverage and patient choice of tested programs. RESULTS: We found strength-duration parameters of chronaxie and rheobase to be 295 (242 - 326) microseconds and 2.5 (1.3 - 3.3) mA, respectively. The median PW of all patients' 'walk-out' programs was 400 microseconds, approximately 48% higher than median chronaxie (p = 0.01), suggesting that chronaxie may not relate to patient-preferred stimulation settings. We found that 7/19 patients selected new PW programs, which significantly increased their paresthesia-pain overlap by 56% on average (p = 0.047). We estimated that 10/19 patients appeared to have greater paresthesia coverage, and 8/19 patients appeared to display a 'caudal shift' of paresthesia coverage with increased PW. LIMITATIONS: Small number of patients. CONCLUSIONS: Variable PW programming in SCS appears to have clinical value, demonstrated by some patients improving their paresthesia-pain overlap, as well as the ability to increase and even 'steer' paresthesia coverage.

Theoretical investigation into longitudinal cathodal field steering in spinal cord stimulation.

Objective. When using spinal cord stimulation (SCS) for chronic pain management, precise longitudinal positioning of the cathode is crucial to generate an electrical field capable of targeting the neural elements involved in pain relief. Presently used methods have a poor spatial resolution and lack postoperative flexibility needed for fine tuning and reprogramming the stimulation field after lead displacement or changes in pain pattern. We describe in this article a new method, "electrical field steering," to control paresthesia in SCS. The method takes advantage of newer stimulator design and a programming technique allowing for "continuous" adjustment of contact combination while controlling stimulation current for each contact separately. Method. Using computer modeling we examined how stimulation of dorsal column (DC) and dorsal root (DR) fibers was influenced by changing the current ratio of the cathodes of a dual (--) and a guarded dual cathode (+--+) configuration programmed on a percutaneous lead with 9 and 4 mm center-to-center contact spacing. Results. A cathodal current ratio could be found for which DC or DR fiber recruitment and thus, most likely, paresthesia coverage was maximized. The DR threshold profiles shifted longitudinally, thus following the shift in the electrical field during steering. The profiles had a constant shape when the contact spacing was small and a varying shape for wider contact separation. Generally, the wider contact separation provided less DC and more DR fiber recruitment. Conclusions. By means of cathodal steering on a longitudinal contact array, the group of excited DC and DR fibers, and thus paresthesia coverage, can be controlled when using SCS. With widely spaced contacts, superposition of the electrical field from each steering contact is limited. To precisely control segmental paresthesia (DR stimulation), a small contact spacing is necessary.

Factors affecting impedance of percutaneous leads in spinal cord stimulation.

Objectives. Although the load impedance of a pulse generator has a significant effect on battery life, the electrical impedance of contact arrays in spinal cord stimulation (SCS) has not been extensively studied. We sought to characterize the typical impedance values measured from common quadripolar percutaneous SCS contact arrays. Methods. In 36 patients undergoing percutaneous trial stimulation for various chronic pain conditions, bipolar impedance between adjacent contacts of 64 leads with 9 mm center-to-center spacing was measured in two different vertebral level regions, cervical (C3-C7) and lower-thoracic (T7-T12). Multiple linear regression was applied to analyze the contribution of six variables to the biological tissue portion of the impedance (excluding the resistance of the lead wires). Results. The median impedance in the cervical region (351 ± 90 Ω) was significantly lower (36%, p < 0.001) than in the lower-thoracic region (547 ± 151 Ω). In addition, time since implant had a weaker but still significant effect on tissue impedance. Conclusions. Results from finite-difference mathematical modeling of SCS suggest that the difference in tissue impedance related to vertebral level may be due to the dorsoventral position of the lead in the epidural space. The presence of a larger space between the triangularly shaped dorsal part of the vertebral arch and the round shape of the dural sac in the lower-thoracic region increases the likelihood that the stimulating lead will not make dural contact, and thus "see" an increased impedance from the surrounding epidural fat. This implies that the energy requirements for stimulation in the thoracic region will be higher than in the cervical region, at least during the acute phase of implant.

A preliminary feasibility study of different implantable pulse generators technologies for diaphragm pacing system.

Diaphragm pacing stimulation (DPS) for ventilator-dependent patients provides several advantages over conventional techniques such as phrenic nerve pacing or mechanical ventilator support. To date, the only existing system for DPS uses lead electrodes, percutaneously attached to an external pulse generator (PG). However, for a widespread use of this technique it would be more appropriate to eliminate the need for percutaneous wire and use a totally implantable system. The aim of this study was to determine if it were feasible to replace the external PG by an implantable system. We present here the results of a preliminary study of two different PG, currently used in other electrical stimulation (ES) clinical applications, which could be used as implantable DPS systems. One radio-frequency-powered PG, one rechargeable battery-powered PG, and the current external PG were tested. Each was attached to the externalized part of the wires, connected to the diaphragm and tidal volume (TV) was measured in one ventilator-dependent patient who has been using the current percutaneous stimulator for 3 years. Results indicated that both implantable PGs could achieve equivalent ventilatory requirements to the current external stimulator. No significant differences were observed between the three PG systems when stimulating the electrodes as used in the patient's own chronically attached PG system. We found that TV increased with increases in charge and frequency as expected when stimulating the patient's electrodes individually and in combination with each PG system. These results are a significant step toward developing a totally implantable DPS system for the ventilator-dependant patients. Further clinical tests to demonstrate the safety and efficacy of a fully implanted DPS system are warranted.

Real-Time Paresthesia Steering Using ContinuousElectric Field Adjustment. Part I: IntraoperativePerformance.

We present data collected from a multicenter study using a new neurostimulation system. This new system uses a current-shifting programming technique for spinal cord stimulation. The system maintains a continuous, suprathreshold stimulation field while adjusting the distribution of anodic and cathodic current among contacts along a multi-contact array. The changing distribution of current shifts the electric field along the spinal cord, resulting in real-time, dynamic paresthesia steering. This process of adjusting the stimulation field has been termed continuous electric field adjustment (CEFA). This technique has been used to assess paresthesia coverage for patients undergoing implantation of stimulation contact arrays for chronic pain. This multicenter study evaluated the performance of the CEFA technique. The results of the study showed that paresthesia coverage could be shifted in real-time to different regions on the patient's body in a comfortable fashion, with the patient always feeling paresthesia during the adjustment process. The results of the study also show that the process was time-efficient: intraoperatively, the median time to assess 71 combinations on a single 8-contact lead across 18 patients was 4.1 (3.6-5.0) minutes.