Spinal Cord Stimulation in a Mouse Chronic Neuropathic Pain Model

Truin, Michiel; Venrooij, P. van; Duysens, V.; Deumens, Ronald; Kleef, Maarten van; Joosten, Elbert A.J.

doi:10.1111/j.1525-1403.2007.00124.x

Cited by 7 publications

(7 citation statements)

References 11 publications

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“…In previous mouse studies, a single epidural cathode electrode was used for DCS, with the anode placed in the abdomen. 61 The average motor threshold amplitude reported in that study was 730 μA, which is an order of magnitude greater than what we measured (71 μA). We attribute this discrepancy to the bipolar architecture of our electrode, resulting in more focal electrical fields and greater activation of dorsal column axons while minimizing unwanted heat generation and electrolysis.…”

Section: Discussioncontrasting

confidence: 56%

Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations

2022

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Neurostimulation therapies are frequently used in patients with chronic pain conditions. They emerged from Gate Control Theory (GCT), which posits that Aβ-fiber activation recruits superficial dorsal horn (SDH) inhibitory networks to "close the gate" on nociceptive transmission, resulting in pain relief. However, the efficacy of current therapies is limited, and the underlying circuits remain poorly understood. For example, it remains unknown whether ongoing stimulation of Aβ-fibers is sufficient to drive activity in SDH neurons. We used multiphoton microscopy in spinal cords extracted from mice expressing the genetically encoded calcium indicator GCaMP6s in glutamatergic and GABAergic populations; activity levels were inferred from deconvolved calcium signals using CaImAn software. Sustained Aβ-fiber stimulation at the dorsal columns or dorsal roots drove robust yet transient activation of both SDH populations. Following the initial increase, activity levels decreased below baseline in glutamatergic neurons and were depressed after stimulation ceased in both populations. Surprisingly, only about half of GABAergic neurons responded to Aβ-fiber stimulation. This subset showed elevated activity for the entire duration of stimulation, while non-responders decreased with time. Our findings suggest that Aβ-fiber stimulation initially recruits both excitatory and inhibitory populations but has divergent effects on their activity, providing a foundation for understanding the analgesic effects of neurostimulation devices.

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Section: Discussioncontrasting

confidence: 56%

Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations

2022

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“…Though tonic SCS successfully decreased pain sensitivity, SCS treatment typically did not return pain levels in rats back to pre-injury control levels. In a mouse model, SCS treatment following PSNL lesions proved particularly efficacious, with 80% of mice in one study [34] and 100% of mice in another study [25] responding positively to tonic SCS treatment. In this latter study, unlike the typical rat study, the mice returned to baseline levels of paw withdrawal following SCS treatment.…”

Section: Scs In Partial Nerve Injury Modelsmentioning

confidence: 95%

Animal Pain Models for Spinal Cord Stimulation

Williams¹,

Kelley²,

Vallejo³

et al. 2022

Preclinical Animal Modeling in Medicine

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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.

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“…In subsequent studies that further explored its mechanisms, it was demonstrated that DRG neuromodulation therapy [high-frequency electrical nerve stimulation (HFES)] applied in in vitro (10 kHz, 2 mA) or in vivo (20.6 kHz) systems was able to reduce the production of high-mobility group Box-1 (HMGB1), CGRP, and SP peripherally as well as reduce pain, thus indicating reduced nociceptor neuron activity, suggesting that HFES may reset sensory neurons to a less pro-inflammatory state [ 62 ], highlighting a potential mechanism for the treatment of neuropathic pain. Moreover, in rats with SNI procedure, high-voltage pulsed radiofrequency (HVPRF) in the DRG (L 5 ; 45–100 V) reduced pain and induced autophagy in spinal cord microglia, as well as reduced TNF-α and increased IL-10 were observed in the dorsal horn of the spinal cord, with additional improvements in DRG morphology [ 44 ]. Similar to these findings, DRG electrical stimulation (GFS—ganglionic field stimulation) could attenuate the blood oxygen-level dependent (BOLD) signal response to acute noxious stimulation in brain regions associated with painful stimuli in a rat model [ 105 ].…”

Section: Neuromodulation Therapies Targeting Drg and The Spinal Cord ...mentioning

confidence: 99%

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain

da Silva,

Martelossi-Cebinelli,

Yaekashi

et al. 2024

Brain Sciences

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Neuropathic pain arises from injuries to the nervous system in diseases such as diabetes, infections, toxicity, and traumas. The underlying mechanism of neuropathic pain involves peripheral and central pathological modifications. Peripheral mechanisms entail nerve damage, leading to neuronal hypersensitivity and ectopic action potentials. Central sensitization involves a neuropathological process with increased responsiveness of the nociceptive neurons in the central nervous system (CNS) to their normal or subthreshold input due to persistent stimuli, leading to sustained electrical discharge, synaptic plasticity, and aberrant processing in the CNS. Current treatments, both pharmacological and non-pharmacological, aim to alleviate symptoms but often face challenges due to the complexity of neuropathic pain. Neuromodulation is emerging as an important therapeutic approach for the treatment of neuropathic pain in patients unresponsive to common therapies, by promoting the normalization of neuronal and/or glial activity and by targeting cerebral cortical regions, spinal cord, dorsal root ganglia, and nerve endings. Having a better understanding of the efficacy, adverse events and applicability of neuromodulation through pre-clinical studies is of great importance. Unveiling the mechanisms and characteristics of neuromodulation to manage neuropathic pain is essential to understand how to use it. In the present article, we review the current understanding supporting dorsal root ganglia and spinal cord neuromodulation as a therapeutic approach for neuropathic pain.

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Spinal Cord Stimulation in a Mouse Chronic Neuropathic Pain Model

Cited by 7 publications

References 11 publications

Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations

Dorsal column and root stimulation at Aβ-fiber intensity activate superficial dorsal horn glutamatergic and GABAergic populations

Animal Pain Models for Spinal Cord Stimulation

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain

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