Early high-frequency spinal cord stimulation treatment inhibited the activation of spinal mitogen-activated protein kinases and ameliorated spared nerve injury-induced neuropathic pain in rats

2020 ◽  
Vol 721 ◽  
pp. 134763 ◽  
Author(s):  
Wen-Tzu Liao ◽  
Chia-Chih Tseng ◽  
Chih-Hsien Wu ◽  
Chung-Ren Lin
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Protein Kinases ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Spared Nerve Injury ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

scholarly journals Spinal cord stimulation using differential target multiplexed programming modulates neural cell-specific transcriptomes in an animal model of neuropathic pain

2020 ◽  
Vol 16 ◽  
pp. 174480692096436
Author(s):  
David L Cedeño ◽  
William J Smith ◽  
Courtney A Kelley ◽  
Ricardo Vallejo
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Neural Cell ◽  
High Rate ◽  
Spared Nerve Injury ◽  
Expression Levels ◽  
Injury Model ◽  
Low Rate

Spinal cord stimulation is a proven effective therapy for treating chronic neuropathic pain. Previous work in our laboratory demonstrated that spinal cord stimulation based on a differential target multiplexed programming approach provided significant relief of pain-like behavior in rodents subjected to the spared nerve injury model of neuropathic pain. The relief was significantly better than obtained using high rate and low rate programming. Furthermore, transcriptomics-based results implied that differential target multiplexed programming modulates neuronal–glial interactions that have been perturbed by the pain process. Although differential target multiplexed programming was developed to differentially target neurons and glial cells, our previous work did not address this. This work presents transcriptomes, specific to each of the main neural cell populations (neurons, microglia, astrocytes, and oligodendrocytes), obtained from spinal cord subjected to continuous spinal cord stimulation treatment with differential target multiplexed programming, high rate programming, or low rate programming compared with no spinal cord stimulation treatment, using the spared nerve injury model. To assess the effect of each spinal cord stimulation treatment on these cell-specific transcriptomes, gene expression levels were compared with that of healthy animals, naïve to injury and interventional procedures. Pearson correlations and cell population analysis indicate that differential target multiplexed programming yielded strong and significant correlations to expression levels found in the healthy animals across every evaluated cell-specific transcriptome. In contrast, high rate programming only yielded a strong correlation for the microglia-specific transcriptome, while low rate programming did not yield strong correlations with any cell types. This work provides evidence that differential target multiplexed programming distinctively targeted and modulated the expression of cell-specific genes in the direction of the healthy state thus supporting its previously established action on regulating neuronal–glial interaction processes in a pain model.

scholarly journals Spinal Cord Stimulation Attenuates Mechanical Allodynia and Increases Central Resolvin D1 Levels in Rats With Spared Nerve Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueshu Tao ◽  
Xin Luo ◽  
Tianhe Zhang ◽  
Brad Hershey ◽  
Rosana Esteller ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Mechanical Allodynia ◽  
Male Rat ◽  
Dependent Manner ◽  
Spared Nerve Injury ◽  
Resolvin D1 ◽  
Cold Allodynia

Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and this stimulation alone was sufficient to effectively reduce nerve injury-induced mechanical allodynia during stimulation without affecting SNI-induced cold allodynia. SCS alone significantly reduced interleukin-1β levels in both serum and CSF samples. Strikingly, SCS significantly increased RvD1 levels in the CSF but not serum. Finally, intrathecal injection of RvD1 (100 and 500 ng, i.t.) 4 weeks after nerve injury reduced SNI-induced mechanical allodynia in a dose-dependent manner. Our findings suggest that 1 kHz SCS may alleviate neuropathic pain via reduction of IL-1β and via production and/or release of RvD1 to control SNI-induced neuroinflammation.

scholarly journals 1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chiaki Yamada ◽  
Aiko Maeda ◽  
Katsuyuki Matsushita ◽  
Shoko Nakayama ◽  
Kazuhiro Shirozu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Cervical Vertebrae ◽  
Intractable Pain ◽  
Target Area ◽  
Positive Effects ◽  
Cord Injury

Abstract Background Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. Case presentation A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. Conclusions SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

scholarly journals Suppression of Superficial Microglial Activation by Spinal Cord Stimulation Attenuates Neuropathic Pain Following Sciatic Nerve Injury in Rats

2020 ◽  
Vol 21 (7) ◽  
pp. 2390
Author(s):  
Masamichi Shinoda ◽  
Satoshi Fujita ◽  
Shiori Sugawara ◽  
Sayaka Asano ◽  
Ryo Koyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Electrical Stimulation ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Spinal Cord Stimulation ◽  
Microglial Activation ◽  
In Vivo Optical Imaging ◽  
Stimulation Of

We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.

scholarly journals Comparison of FDA-Approved Electrical Neuromodulation Techniques for Focal Neuropathic Pain: A Narrative Review of DRG, HF10, and Burst Neuromodulation

2021 ◽  
pp. E407-E423
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Dorsal Root ◽  
Case Reports ◽  
Case Series ◽  
Dorsal Column ◽  
Small Sample

BACKGROUND: Evidence suggests that dorsal root ganglion stimulation (DRGS) is a more effective treatment for focal neuropathic pain (FNP) compared with tonic, paresthesia-based dorsal column spinal cord stimulation (SCS). However, new advancements in waveforms for dorsal column SCS have not been thoroughly studied or compared with DRGS for the treatment of FNP. OBJECTIVES: The purpose of this review was to examine the evidence for these novel technologies; to highlight the lack of high-quality evidence for the use of neuromodulation to treat FNP syndromes other than complex regional pain syndrome I or II of the lower extremity; to emphasize the absence of comparison studies between DRGS, burst SCS, and high-frequency SCS; and to underscore that consideration of all neuromodulation systems is more patient-centric than a one-size-fits-all approach. STUDY DESIGN: This is a review article summarizing case reports, case series, retrospective studies, prospective studies, and review articles. SETTING: The University of Miami, Florida. METHODS: A literature search was conducted from February to March 2020 using the PubMed and EMBASE databases and keywords related to DRGS, burst SCS, HF10 (high-frequency of 10 kHz), and FNP syndromes. All English-based literature from 2010 reporting clinical data in human patients were included. RESULTS: Data for the treatment of FNP using burst SCS and HF10 SCS are limited (n = 11 for burst SCS and n = 11 for HF10 SCS). The majority of these studies were small, single-center, nonrandomized, noncontrolled, retrospective case series and case reports with short follow-up duration. To date, there are only 2 randomized controlled trials for burst and HF10 for the treatment of FNP. LIMITATIONS: No studies were available comparing DRGS to HF10 or burst for the treatment of FNP. Data for the treatment of FNP using HF10 and burst stimulation were limited to a small sample size reported in mostly case reports and case series. CONCLUSIONS: FNP is a complex disease, and familiarity with all available systems allows the greatest chance of success. KEY WORDS: Dorsal root ganglion, high frequency, burst, spinal cord stimulation, neuromodulation, focal neuropathic pain

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