scholarly journals Animal Pain Models for Spinal Cord Stimulation

2021 ◽  
Author(s):  
Joseph M. Williams ◽  
Courtney A. Kelley ◽  
Ricardo Vallejo ◽  
David C. Platt ◽  
David L. Cedeño
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Mechanism Of Action ◽  
Spinal Cord Stimulation ◽  
Spinal Nerve ◽  
Animal Pain ◽  
Injury Model ◽  
Pain Models ◽  
Electrical Neuromodulation

Spinal cord stimulation (SCS) is an electrical neuromodulation technique with proven effectiveness and safety for the treatment of intractable chronic pain in humans. Despite its widespread use, the mechanism of action is not fully understood. Animal models of chronic pain, particularly rodent-based, have been adapted to study the effect of SCS on pain-like behavior, as well as on the electrophysiology and molecular biology of neural tissues. This chapter reviews animal pain models for SCS, emphasizing on findings relevant to advancing our understanding of the mechanism of action of SCS, and highlighting the contribution of the animal model to advance clinical outcomes. The models described include those in which SCS has been coupled to neuropathic pain models in rats and sheep based on peripheral nerve injuries, including the chronic constriction injury (CCI) model and the spared nerve injury model (SNI). Other neuropathic pain models described are the spinal nerve ligation (SNL) for neuropathic pain of segmental origin, as well as the chemotherapy-induced and diabetes-induced peripheral neuropathy models. We also describe the use of SCS with inflammatory pain and ischemic pain models.

scholarly journals Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain

2021 ◽  
Vol 2 ◽  
Author(s):  
David L. Cedeño ◽  
Courtney A. Kelley ◽  
Krishnan Chakravarthy ◽  
Ricardo Vallejo
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Glial Cells ◽  
Mechanism Of Action ◽  
Spinal Cord Stimulation ◽  
Expression Levels ◽  
Gate Control Theory

Glial cells play an essential role in maintaining the proper functioning of the nervous system. They are more abundant than neurons in most neural tissues and provide metabolic and catabolic regulation, maintaining the homeostatic balance at the synapse. Chronic pain is generated and sustained by the disruption of glia-mediated processes in the central nervous system resulting in unbalanced neuron–glial interactions. Animal models of neuropathic pain have been used to demonstrate that changes in immune and neuroinflammatory processes occur in the course of pain chronification. Spinal cord stimulation (SCS) is an electrical neuromodulation therapy proven safe and effective for treating intractable chronic pain. Traditional SCS therapies were developed based on the gate control theory of pain and rely on stimulating large Aβ neurons to induce paresthesia in the painful dermatome intended to mask nociceptive input carried out by small sensory neurons. A paradigm shift was introduced with SCS treatments that do not require paresthesia to provide effective pain relief. Efforts to understand the mechanism of action of SCS have considered the role of glial cells and the effect of electrical parameters on neuron–glial interactions. Recent work has provided evidence that SCS affects expression levels of glia-related genes and proteins. This inspired the development of a differential target multiplexed programming (DTMP) approach using electrical signals that can rebalance neuroglial interactions by targeting neurons and glial cells differentially. Our group pioneered the utilization of transcriptomic and proteomic analyses to identify the mechanism of action by which SCS works, emphasizing the DTMP approach. This is an account of evidence demonstrating the effect of SCS on glia-mediated processes using neuropathic pain models, emphasizing studies that rely on the evaluation of large sets of genes and proteins. We show that SCS using a DTMP approach strongly affects the expression of neuron and glia-specific transcriptomes while modulating them toward expression levels of healthy animals. The ability of DTMP to modulate key genes and proteins involved in glia-mediated processes affected by pain toward levels found in uninjured animals demonstrates a shift in the neuron–glial environment promoting analgesia.

Experimental Spinal Cord Stimulation and Neuropathic Pain: Mechanism of Action, Technical Aspects, and Effectiveness

Pain Practice ◽  
2012 ◽  
Vol 13 (2) ◽  
pp. 154-168 ◽  
Author(s):  
Helwin Smits ◽  
Maarten van Kleef ◽  
Jan Holsheimer ◽  
Elbert A. J. Joosten
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Mechanism Of Action ◽  
Spinal Cord Stimulation ◽  
Technical Aspects ◽  
Pain Mechanism

scholarly journals P.153 Profiles and Outcomes of Workers’ Compensation Patients Undergoing Spinal Cord Stimulation for Persistent Post Surgical Pain

2021 ◽  
Vol 48 (s3) ◽  
pp. S63-S64
Author(s):  
V Varshney ◽  
R Sahjpaul ◽  
J Osborn
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Pain Management ◽  
Retrospective Analysis ◽  
Spinal Cord Stimulation ◽  
Workers Compensation ◽  
Low Back ◽  
Chronic Pain Management ◽  
Surgical Pain

Background: The challenges of chronic pain management, and resulting poorer outcomes, in workers’ compensation (WCB) patients has been well established. Spinal cord stimulation (SCS) has been used for the management of low back and radicular neuropathic pain with varying effectiveness and it’s efficacy in the WCB population has been challenged. We sought to examine our experience using SCS in WCB compared to non WCB patients. Methods: A retrospective analysis of 71 WCB patients assessed and treated at the St Pauls Hospital neuromodulation program between 2016-2021 was performed. This group was compared to a cohort on non WCB patients in terms of the likelhood of being offered a trial, proceeding with trial if offered, and the likelhood of a successful trial proceeding to implant. Results: Compared to non WCB, the WCB patients were more likely to be offered a trial (86% vs 77%) and more likely to proceed with a trial if offered (82% vs 71%). Trial to implant ratios were similar in both WCB and non WCB patients (78% vs 77%). Conclusions: WCB patients were more likely to be offered a SCS trial and more likely to accept if offered, compared to non-WCB patients. However, both groups were similar in trial to implant probability.

scholarly journals SPINAL CORD STIMULATION IN TREATMENT OF THE NEUROPATHIC PAIN SYNDROMES: INITIAL EXPERIENCE

2010 ◽  
Vol 16 (2) ◽  
pp. 68-71
Author(s):  
D. A. Rzaev ◽  
V. V. Rudenko ◽  
I. L. Pudovkin ◽  
A. P. Tatarintsev ◽  
D. S. Godanyuk
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
Pulse Generator ◽  
Initial Experience ◽  
Pain Syndromes ◽  
Chronic Pain Syndromes

In the article initial experience of spinal cord stimulation for chronic pain syndromes is described. The trial was done for 62 patients, in 52 cases trial was successful and subcutaneous pulse generator were implanated. Maximal follow-up is 26 months. The level of pain evaluates at VAS. Permanent pain-relieve results were achieved in 46 patients (74,2%). These results correspond to literature data.

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 Modulation of microglial activation states by spinal cord stimulation in an animal model of neuropathic pain: Comparing high rate, low rate, and differential target multiplexed programming

2021 ◽  
Vol 17 ◽  
pp. 174480692199901
Author(s):  
William J Smith ◽  
David L Cedeño ◽  
Samuel M Thomas ◽  
Courtney A Kelley ◽  
Francesco Vetri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
Microglial Activation ◽  
High Rate ◽  
Expression Levels ◽  
Transcriptomic Changes ◽  
Low Rate

While numerous studies and patient experiences have demonstrated the efficacy of spinal cord stimulation as a treatment for chronic neuropathic pain, the exact mechanism underlying this therapy is still uncertain. Recent studies highlighting the importance of microglial cells in chronic pain and characterizing microglial activation transcriptomes have created a focus on microglia in pain research. Our group has investigated the modulation of gene expression in neurons and glial cells after spinal cord stimulation (SCS), specifically focusing on transcriptomic changes induced by varying SCS stimulation parameters. Previous work showed that, in rodents subjected to the spared nerve injury (SNI) model of neuropathic pain, a differential target multiplexed programming (DTMP) approach provided significantly better relief of pain-like behavior compared to high rate (HRP) and low rate programming (LRP). While these studies demonstrated the importance of transcriptomic changes in SCS mechanism of action, they did not specifically address the role of SCS in microglial activation. The data presented herein utilizes microglia-specific activation transcriptomes to further understand how an SNI model of chronic pain and subsequent continuous SCS treatment with either DTMP, HRP, or LRP affects microglial activation. Genes for each activation transcriptome were identified within our dataset and gene expression levels were compared with that of healthy animals, naïve to injury and interventional procedures. Pearson correlations indicated that DTMP yields the highest significant correlations to expression levels found in the healthy animals across all microglial activation transcriptomes. In contrast, HRP or LRP yielded weak or very weak correlations for these transcriptomes. This work demonstrates that chronic pain and subsequent SCS treatments can modulate microglial activation transcriptomes, supporting previous research on microglia in chronic pain. Furthermore, this study provides evidence that DTMP is more effective than HRP and LRP at modulating microglial transcriptomes, offering potential insight into the therapeutic efficacy of DTMP.

scholarly journals High Level of Childhood Trauma Predicts a Poor Response to Spinal Cord Stimulation in Chronic Neuropathic Pain

2019 ◽  
Vol 1 (22;1) ◽  
pp. E37-E44
Author(s):  
Jaakko Määttä
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Risk Factor ◽  
Back Pain ◽  
Childhood Trauma ◽  
Spinal Cord Stimulation ◽  
Post Surgery ◽  
Distress Scale ◽  
Trauma Group

Background: Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients. Objectives: The objective of this prospective registry-based study was to investigate the prevalence of 5 domains of childhood trauma (emotional neglect, emotional abuse, physical neglect, physical abuse, and sexual abuse) and their relationship with the outcome of spinal cord stimulation on patients suffering from treatment-resistant chronic pain. Methods: SCS patients treated at Kuopio University Hospital between 1/1/2015 and 12/31/2016 were sent a survey in the mail, the Trauma and Distress Scale, assessing childhood trauma (n = 43). Neuropathic pain, disability, anxiety, and depression were measured in the patients pre-surgery and at 6 and 12 months post-surgery. The patients who provided their name on the questionnaire (n = 22) and had suffered from 3 or more domains of trauma were grouped as the high-trauma group (n = 13) and the rest as the low-trauma group (n = 9). Results: The questionnaire was completed by 40 patients (93%). At least 1 domain of trauma was experienced by 35 (88%) patients, and at least 2 by 24 (60%). The low-trauma group displayed a statistically significant decrease in the mean PainDETECT score from 21.5 before SCS to 16.5 at 12 months post-surgery (Wilk’s lambda = 0.297, F(2,9) = 10.6, P = 0.004), contrary to the hightrauma group (Wilk’s lambda = 0.904, F(2,6) = 0.3, P = 0.739). Limitations: Only 22 of the 40 patients provided their name on the questionnaire, which decreased the sample size on follow-up. Conclusion: This was the first study to investigate childhood trauma in SCS patients. Patients who had experienced high amounts of childhood trauma did not experience any relief from neuropathic pain 12 months’ post-SCS, contrary to the low-trauma group. Childhood trauma might be a factor worth screening in the preoperative evaluation and aftercare of SCS candidates. Key words: Spinal cord stimulation, the Trauma and Distress Scale, chronic pain, childhood trauma, childhood abuse, childhood neglect, chronic back pain, back pain, psychological distress, neuropathic pain

Sign in / Sign up

Export Citation Format

Share Document