Human Dorsal Root Ganglion Stimulation Reduces Sympathetic Outflow and Long-Term Blood Pressure

Sverrisdóttir, Yrsa Bergmann; Martin, Sean; Hadjipavlou, George; Kent, Alexander R.; Paterson, David J.; FitzGerald, James J.; Green, Alexander L.

doi:10.1016/j.jacbts.2020.07.010

Cited by 29 publications

(13 citation statements)

References 37 publications

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“…Our results show that DRGS reduced the cardiac sympathetic output via controlling the afferent arm of the cardio-neural reflex. In support of our results, a recent study has demonstrated that left-sided DRGS lowers sympathetic nerve activity by significantly reducing the firing frequency of sympathetic nerves (Sverrisdottir et al, 2020).…”

Section: Dorsal Root Ganglion Stimulation Modulation Of Cardiac Sympathetic Activity and Ventricular Excitabilitysupporting

confidence: 92%

“…Bioelectronic dorsal root ganglion stimulation (DRGS) is a novel approach to neuromodulation therapy, targeting these neural structures that contain the axons and cell bodies of afferent neurons, located at the distal end of the dorsal root of the spinal cord (Sverrisdottir et al, 2020). Early evidence suggests that DRGS is an effective treatment for some pain syndromes, clinically and preclinically (Liem et al, 2015;Deer et al, 2019;Yu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

et al. 2021

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Introduction: Sympathetic hyperactivity is strongly associated with ventricular arrhythmias and sudden cardiac death. Neuromodulation provides therapeutic options for ventricular arrhythmias by modulating cardiospinal reflexes and reducing sympathetic output at the level of the spinal cord. Dorsal root ganglion stimulation (DRGS) is a recent neuromodulatory approach; however, its role in reducing ventricular arrhythmias has not been evaluated. The aim of this study was to determine if DRGS can reduce cardiac sympathoexcitation and the indices for ventricular arrhythmogenicity induced by programmed ventricular extrastimulation. We evaluated the efficacy of thoracic DRGS at both low (20 Hz) and high (1 kHz) stimulation frequencies.Methods: Cardiac sympathoexcitation was induced in Yorkshire pigs (n = 8) with ventricular extrastimulation (S1/S2 pacing), before and after DRGS. A DRG-stimulating catheter was placed at the left T2 spinal level, and animals were randomized to receive low-frequency (20 Hz and 0.4 ms) or high-frequency (1 kHz and 0.03 ms) DRGS for 30 min. High-fidelity cardiac electrophysiological recordings were performed with an epicardial electrode array measuring the indices of ventricular arrhythmogenicity—activation recovery intervals (ARIs), electrical restitution curve (Smax), and Tpeak–Tend interval (Tp-Te interval).Results: Dorsal root ganglion stimulation, at both 20 Hz and 1 kHz, decreased S1/S2 pacing-induced ARI shortening (20 Hz DRGS −21±7 ms, Control −50±9 ms, P = 0.007; 1 kHz DRGS −13 ± 2 ms, Control −46 ± 8 ms, P = 0.001). DRGS also reduced arrhythmogenicity as measured by a decrease in Smax (20 Hz DRGS 0.5 ± 0.07, Control 0.7 ± 0.04, P = 0.006; 1 kHz DRGS 0.5 ± 0.04, Control 0.7 ± 0.03, P = 0.007), and a decrease in Tp-Te interval/QTc (20 Hz DRGS 2.7 ± 0.13, Control 3.3 ± 0.12, P = 0.001; 1 kHz DRGS 2.8 ± 0.08, Control; 3.1 ± 0.03, P = 0.007).Conclusions: In a porcine model, we show that thoracic DRGS decreased cardiac sympathoexcitation and indices associated with ventricular arrhythmogenicity during programmed ventricular extrastimulation. In addition, we demonstrate that both low-frequency and high-frequency DRGS can be effective neuromodulatory approaches for reducing cardiac excitability during sympathetic hyperactivity.

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Section: Dorsal Root Ganglion Stimulation Modulation Of Cardiac Sympathetic Activity and Ventricular Excitabilitysupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

et al. 2021

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“…There is much to be learned about DRG stimulation as therapeutic tool. A recent report describes that DRG stimulation reduces sympathetic muscle traffic [ 26 ]. This lowered sympathetic outflow may benefit fibromyalgia patients.…”

Section: Future Directionsmentioning

confidence: 99%

Dorsal root ganglia: fibromyalgia pain factory?

Martı́nez-Lavı́n

2021

Clin Rheumatol

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This perspective article focuses on dorsal root ganglia (DRG) as potential fibromyalgia main pain source. Humans possess 31 pairs of DRG lying along the spine. These ganglia have unique anatomical and physiological features. During development, DRG are extruded from the central nervous system and from the blood-brain barrier but remain surrounded by meningeal layers and by cerebrospinal fluid. DRG house the pain-transmitting small nerve fiber nuclei; each individual nucleus is tightly enveloped by metabolically active glial cells. DRG possess multiple inflammatory/pro-nociceptive molecules including ion channels, neuropeptides, lymphocytes, and macrophages. DRG neurons have pseudo-unipolar structure making them able to generate pain signals; additionally, they can sequester antigen-specific antibodies thus inducing immune-mediated hyperalgesia. In rodents, diverse physical and/or environmental stressors induce DRG phenotypic changes and hyperalgesia. Unfolding clinical evidence links DRG pathology to fibromyalgia and similar syndromes. Severe fibromyalgia is associated to particular DRG ion channel genotype. Myalgic encephalomyelitis patients with comorbid fibromyalgia have exercise-induced DRG pro-nociceptive molecules gene overexpression. Skin biopsy demonstrates small nerve fiber pathology in approximately half of fibromyalgia patients. A confocal microscopy study of fibromyalgia patients disclosed strong correlation between corneal denervation and small fiber neuropathy symptom burden. DRG may be fibromyalgia neural hub where different stressors can be transformed in neuropathic pain. Novel neuroimaging technology and postmortem inquest may better define DRG involvement in fibromyalgia and similar maladies. DRG pro-nociceptive molecules are attractive fibromyalgia therapeutic targets.

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“…In preclinical pain models, sympathetic sprouting in DRG has been observed and sympathetic stimulation modulates DRG neuronal activity [ 59 ]. Moreover, DRG stimulation can also influence the activity of sympathetic nerves [ 61 ]. In addition, the majority of DRG neurons undergo depolarization when the axon of a neighboring DRG neuron within the same ganglion is stimulated [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma

Barr

Kruse

Restaino

et al. 2021

Cells

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Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.

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Human Dorsal Root Ganglion Stimulation Reduces Sympathetic Outflow and Long-Term Blood Pressure

Abstract: Visual Abstract

Cited by 29 publications

References 37 publications

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

Neuromodulation With Thoracic Dorsal Root Ganglion Stimulation Reduces Ventricular Arrhythmogenicity

Dorsal root ganglia: fibromyalgia pain factory?

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma

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