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

Lee, Kwan Yeop; Bae, Chilman; Lee, Dong Chul; Kagan, Zachary; Bradley, Kerry; Chung, Jin Mo; La, Jun–Ho

doi:10.1016/j.neuroscience.2019.12.031

Cited by 66 publications

(48 citation statements)

References 35 publications

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“…The large difference in effect size between the 10 kHz treatment group and the conventional control group suggests a different or additional mechanism of action(s) for 10 kHz stimulation. 12 This is supported by multiple subsequent observational studies demonstrating clinical improvement with 10 kHz stimulation in patients who previously failed conventional SCS. [9][10][11] A previously published case series demonstrated improvement with temporary lead placement and 10 kHz SCS in patients who failed previous traditional low frequency SCS implantation.…”

Section: Resultsmentioning

confidence: 77%

<p>Retrospective Assessment of Salvage to 10 kHz Spinal Cord Stimulation (SCS) in Patients Who Failed Traditional SCS Therapy: RESCUE Study</p>

Kapural¹,

Sayed²,

Kim³

et al. 2020

JPR

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Background and Objectives A randomized clinical trial demonstrated that 10 kHz SCS (10kHz-SCS) therapy is superior to traditional low-frequency SCS (LF-SCS) at 12- and 24-month clinical follow-ups and led to Food and Drug Administration (FDA) approval of the therapy. The results of the study led our practices to trial 10kHz-SCS in patients who had not maintained pain relief with LF-SCS therapy. Here, we report a large set of data from two clinical sites to assess if 10kHz-SCS is an effective salvage modality when LF-SCS fails. Methods We conducted a retrospective chart review of 120 patients across two clinical sites who had LF-SCS implants and were salvaged with 10kHz-SCS. Results Data were analyzed from 105 patients between 28 and 90 years old (median 60) with chronic pain for 13.6 years. The mean duration of LF-SCS therapy was 4.66±3.9 years. The average Visual Analog Scale (VAS) decreased from 8.30±1.4 (median of 8) cm to 3.32±2.0 (median of 3) cm at 12 months and 3.36±2.0 (median of 3) cm at the most recent clinic visit (p<0.001) following salvage therapy. Pain relief of 50% or more was obtained in 85 out of 105 (81%) patients. Opioid usage decreased from 60.3±77.1 mg to 32.1±44.0 mg MSO4 equivalents (p = 0.001) at 12 months after salvage therapy. Conclusion Eighty-one percent of patient cases reviewed, where LF-SCS had failed, achieved >50% pain relief with 10kHz-SCS, and almost all exhibited some clinical improvement. Therefore, 10kHz-SCS should be considered an appropriate option to rescue failed LF-SCS.

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Section: Resultsmentioning

confidence: 77%

<p>Retrospective Assessment of Salvage to 10 kHz Spinal Cord Stimulation (SCS) in Patients Who Failed Traditional SCS Therapy: RESCUE Study</p>

Kapural¹,

Sayed²,

Kim³

et al. 2020

JPR

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“…All recordings showing polysynaptic response were disregarded. The neurons were characterized by their action potential (AP)-firing pattern upon depolarizing current injections in the current clamp mode (5).…”

Section: Western Blotting Analysismentioning

confidence: 99%

“…Among over 38 million people living with HIV-1/AIDS (PLWHA) worldwide, more than 50% develop chronic pain 3,4 . Even in post-cART (combinatorial anti-retroviral therapy) era, HIVassociated pain remains highly prevalent 3,5 , continues to have a major impact on the quality of life of the patients 6 , and is still a central clinical and public health concern 4,7 . The HIV-associated pain syndrome is manifested in various forms, including peripheral neuropathy, headache and visceral pain, and is often undertreated.…”

Section: Introductionmentioning

confidence: 99%

“…Early studies indicate a correlation between HIV-1 viral load and pain development. However, pain remains highly prevalent in the post cART era 3,5 , indicating viral replication and infection suppressed by antiretroviral drugs are not the major cause responsible for the pain pathogenesis 2 . Both HIV-1 neurotoxic proteins and cART are thought to play crucial roles in the pain pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism and role of astrogliosis in the pathogenesis of HIV-associated pain One Sentence Summary: Neuron-to-astrocyte Wnt5a signaling-activated astrogliosis is essential for the development of pathological pain induced by HIV-1 gp120

Liu

Gelman

et al. 2021

Preprint

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Pathological pain is the most common neurological disorder in people living with HIV-1/AIDS (PLWHA), and rationale-based effective treatment is not available. Multiple neuropathologies develop in the pain transmission pathways in of HIV patients, consistent with their nociceptive dysfunction1,2. One of the prominent neuropathologies associating with the manifestation of pain in HIV patients is astrogliosis (a.k.a. reactive astrocytes) in the spinal dorsal horn (SDH)1, the spinal center for the transmission of pain signals from peripheral organs to the brain. However, the pathogenic role and the activation mechanism of astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain pathogenesis induced by HIV-1 gp120, a key etiologically relevant protein2, and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. We found that ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization (NCP) in the SDH. In addition, we demonstrated that conditional knockout (CKO) of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also the hyperalgesia and the NCP. Furthermore, we found that the astrogliosis promoted expression of the NCP and the hyperalgesia via IL-1β regulated by a Wnt5a-ROR2-MMP2 axis. Our results elucidate an important role and a novel mechanism of astrogliosis in the pathogenesis of HIV-associated pain. Targeting reactive astrocytes by manipulating the mechanistic processes identified here may lead to the development of effective therapy to treat the pain syndrome in HIV patients.

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“…High carrier frequency epidural stimulation may modulate recruitment patters of afferent fibers and activation of interspinal neurons [51][52][53] , but the mechanism of sensory control remains unclear.…”

Section: Noxious Sensations Of Epidural Stimulation Were Controlled Umentioning

confidence: 99%

This preprint has been taken down.

2020

Preprint

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Brain-computer interfaces (BCIs) for treatment of spinal cord injury (SCI) can be used to reanimate paralyzed limbs. Most approaches stimulate the peripheral nerves or muscles, which has limitations. To overcome these challenges, here we show that a BCI can control spinal stimulation and improve forelimb function in rats with cervical SCI. We decoded forelimb movement intention via multichannel local field potentials in sensorimotor cortex using a canonical correlation analysis, which is both less computationally complex and more stable over time than spike-based algorithms. We then used this decoded signal to modulate epidural stimulation and restore forelimb movement. Finally, we implemented the efficient closed-loop algorithm in a miniaturized on-board computing platform. This Brain-Computer-Spinal Interface (BCSI) approach utilized recording and stimulation approaches already used in separate clinical trials, so it may readily translate to human subjects as a potential solution to upper extremity paralysis.

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

Cited by 66 publications

References 35 publications

<p>Retrospective Assessment of Salvage to 10 kHz Spinal Cord Stimulation (SCS) in Patients Who Failed Traditional SCS Therapy: RESCUE Study</p>

<p>Retrospective Assessment of Salvage to 10 kHz Spinal Cord Stimulation (SCS) in Patients Who Failed Traditional SCS Therapy: RESCUE Study</p>

Mechanism and role of astrogliosis in the pathogenesis of HIV-associated pain One Sentence Summary: Neuron-to-astrocyte Wnt5a signaling-activated astrogliosis is essential for the development of pathological pain induced by HIV-1 gp120

This preprint has been taken down.

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