Spinal Cord Stimulation for Treating Chronic Pain: Reviewing Preclinical and Clinical Data on Paresthesia-Free High-Frequency Therapy

Chakravarthy, Krishnan; Richter, Hira C; Christo, Paul J.; Williams, Kayode; Guan, Yun

doi:10.1111/ner.12721

Cited by 93 publications

(108 citation statements)

References 73 publications

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“…Paresthesia‐free SCS applied at ultra‐high frequency (10 kHz) provides improved pain relief as compared to traditional SCS and is a technological advance in the neuromodulation field . By performing behavioral tests in neuropathic rats, we provide proof of principle that using low‐frequency subthreshold SCS and longer pulse widths could be a more energy efficient stimulation paradigm for inhibition of mechanical hypersensitivity, as compared to high‐frequency stimulation.…”

Section: Discussionmentioning

confidence: 95%

“…If a positive response occurred (e.g., abrupt paw withdrawal, licking, and shaking), the next smaller von Frey hair was used; if a negative response was observed, the next higher force was used. The test was continued until the responses to five stimuli were assessed after the first crossing of the withdrawal threshold or the upper/lower end of the von Frey hair set was reached before a positive/negative response had been obtained. The paw withdrawal threshold (PWT) was determined according to the Dixon formula .…”

Section: Methodsmentioning

confidence: 99%

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The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

Chen

Huang

Yang

et al. 2019

Neuromodulation: Technology at the Neural Interface

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Objectives Spinal cord stimulation (SCS) represents an important neurostimulation therapy for pain. A new ultra‐high frequency (10,000 Hz) SCS paradigm has shown improved pain relief without eliciting paresthesia. We aim to determine whether sub‐sensory threshold SCS of lower frequencies also can inhibit mechanical hypersensitivity in nerve‐injured rats and examine how electric charge delivery of stimulation may affect pain inhibition by different patterns of subthreshold SCS. Materials and Methods We used a custom‐made quadripolar electrode (Medtronic Inc., Minneapolis, MN, USA) to provide bipolar SCS epidurally at the T10 to T12 vertebral level. According to previous findings, SCS was tested at 40% of the motor threshold, which is considered to be a sub‐sensory threshold intensity in rats. Paw withdrawal thresholds to punctate mechanical stimulation were measured before and after SCS in rats that received an L5 spinal nerve ligation. Results Both 10,000 Hz (10 kHz, 0.024 msec) and lower frequencies (200 Hz, 1 msec; 500 Hz, 0.5 msec; 1200 Hz; 0.2 msec) of subthreshold SCS (120 min) attenuated mechanical hypersensitivity, as indicated by increased paw withdrawal thresholds after stimulation in spinal nerve ligation rats. Pain inhibition from different patterns of subthreshold SCS was not governed by individual stimulation parameters. However, correlation analysis suggests that pain inhibition from 10 kHz subthreshold SCS in individual animals was positively correlated with the electric charges delivered per second (electrical dose). Conclusions Inhibition of neuropathic mechanical hypersensitivity can be achieved with low‐frequency subthreshold SCS by optimizing the electric charge delivery, which may affect the effect of SCS in individual animals.

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Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

Chen

Huang

Yang

et al. 2019

Neuromodulation: Technology at the Neural Interface

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“…More recently, a number of other stimulation paradigms have been introduced (burst, high-frequency, high-density, etc.) (1,2,(8)(9)(10)(11), promising increased pain control over the tonic stimulation. The vast majority of SCS patients are still treated with tonic stimulation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Tonic Spinal Cord Stimulation on Sensory Perception in Chronic Pain Patients: A Systematic Review

Bordeleau

Cottin

Meier

et al. 2019

Neuromodulation: Technology at the Neural Interface

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“…A few recent outstanding reviews have discussed potential mechanisms of action for pain relief with high‐frequency stimulation, including axonal conduction block, desynchronization of axonal activity, and glial‐neuronal interactions . It was initially believed that HF10 mediates pain relief by blocking or desynchronizing axonal transmission, as shown in peripheral nerves .…”

Section: High‐frequency Stimulationmentioning

confidence: 99%

“…A few recent outstanding reviews have discussed potential mechanisms of action for pain relief with high-frequency stimulation, including axonal conduction block, desynchronization of axonal activity, and glial-neuronal interactions. 17, 145 It was initially believed that HF10 mediates pain relief by blocking or desynchronizing axonal transmission, as shown in peripheral nerves. 146 However, this is an unlikely mechanism, as a computational study demonstrated that the stimulation amplitudes required for activation and conduction block of dorsal column fibers are outside the range used clinically, and patients do not experience paresthesias.…”

Section: Preclinical Mechanistic Studiesmentioning

confidence: 99%

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms

2018

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Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy.

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Spinal Cord Stimulation for Treating Chronic Pain: Reviewing Preclinical and Clinical Data on Paresthesia-Free High-Frequency Therapy

Cited by 93 publications

References 73 publications

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

The Impact of Electrical Charge Delivery on Inhibition of Mechanical Hypersensitivity in Nerve-Injured Rats by Sub-Sensory Threshold Spinal Cord Stimulation

Effects of Tonic Spinal Cord Stimulation on Sensory Perception in Chronic Pain Patients: A Systematic Review

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms

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