A jump-start for electroceuticals

Famm, Kristoffer; Litt, Brian; Tracey, Kevin J.; Boyden, Edward S.; Slaoui, Moncef

doi:10.1038/496159a

Cited by 503 publications

(353 citation statements)

References 10 publications

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“…Stimulating the vagus nerve is intended to balance the aggravated activity of the sympathetic nervous system and the reduced activity of the vagus nerve, which accompanies an increase in the mortality rate among patients with decreased cardiac function. Initial clinical results with these devices are promising and reflect the aim of the recently intensified efforts in bioelectronics to use electrical signals rather than drugs to treat diseases, with the aim of dampening inflammatory processes and repairing functional losses 5, 27…”

Section: Discussionmentioning

confidence: 99%

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

et al. 2017

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AimsBeyond the influence of stimulating devices on cardiac excitation, their use in treating patients with heart failure has positive effects on the myocardium at the molecular level. Electrical signals can induce a wide spectrum of effects in living tissue. Therefore, we sought to determine whether applying electrical microcurrent directly to failing hearts leads to functional improvement.Methods and resultsSixteen male spontaneously hypertensive rats (SHRs) with heart failure underwent application of a patch electrode to the left ventricular epicardium and placement of a subcutaneous counter electrode. The electrode delivered a 0.35 μA microcurrent to nine of the SHRs for 45 ± 3 days; the other seven SHRs were used as controls. At baseline and before the SHRs were humanely put to death, we measured the left ventricular ejection fraction (LVEF) and the thickness of the LV posterior wall during systole and diastole (LVPWs/d). We used quantitative PCR to determine extracellular matrix parameters [collagen I–III, matrix metalloproteinase (MMP)‐2, MMP‐9, tissue inhibitor of metalloproteinases 3 (TIMP3), TIMP4, connexins (Cxs) 40/43/45, transforming growth factor (TGF)‐β, and interleukin (IL)‐6].Among SHRs undergoing microcurrent application, LVEF normalized (mean decrease, 22.8%; P = 0.009), and LVPWs decreased (mean, 35.3%; P = 0.001). Compared with the control group, the SHRs receiving microcurrent exhibited a mean decrease in the gene expression of collagen I (10.6%, P = 0.003), TIMP3 (18.5%, P = 0.005), Cx43 (14.3%, P = 0.003), Cx45 (12.7%, P = 0.020), TGF‐β (13.0%, P = 0.005), and IL‐6 (53.7%, P = 0.000). Microcurrent application induced no changes in the expression of collagen III, MMP‐2, MMP‐9, TIMP4, or Cx40.ConclusionsApplying microcurrent to the LV epicardium of SHRs leads to statistically significant functional improvement and alterations in the levels of inflammatory and extracellular matrix components.

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Section: Discussionmentioning

confidence: 99%

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

et al. 2017

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“…Acupuncture is a minimallyinvasive therapeutic modality that originated in China 2000 years ago as a component of traditional Chinese medicine (Kaptchuk, 2002). While acupuncture therapy is rooted in a complex practice ritual, the acupuncture needle procedure, particularly when coupled with electrical needle stimulation, overlaps significantly with many conventional peripheral neuromodulatory therapies (Langevin et al, 2015) that have generated significant excitement as 'electroceuticals' targeting peripheral nerve receptors (Famm et al, 2013;Waltz, 2016). However, the neurophysiological mechanisms by which acupuncture impacts subjective/psychological (i.e.…”

Section: Introductionmentioning

confidence: 99%

Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture

Maeda

Kim

Kettner

et al. 2017

Brain

134

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Ã These authors contributed equally to this work.Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist. Acupuncture is a minimally-invasive and conservative therapeutic option, and while rooted in a complex practice ritual, acupuncture overlaps significantly with many conventional peripherally-focused neuromodulatory therapies. However, the neurophysiological mechanisms by which acupuncture impacts accepted subjective/psychological and objective/physiological outcomes are not well understood. Eligible patients (n = 80, 65 female, age: 49.3 AE 8.6 years) were enrolled and randomized into three intervention arms: (i) verum electro-acupuncture 'local' to the more affected hand; (ii) verum electro-acupuncture at 'distal' body sites, near the ankle contralesional to the more affected hand; and (iii) local sham electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome Questionnaire assessed pain and paraesthesia symptoms at baseline, following therapy and at 3-month follow-up. Nerve conduction studies assessing median nerve sensory latency and brain imaging data were acquired at baseline and following therapy. Functional magnetic resonance imaging assessed somatotopy in the primary somatosensory cortex using vibrotactile stimulation over three digits (2, 3 and 5). While all three acupuncture interventions reduced symptom severity, verum (local and distal) acupuncture was superior to sham in producing improvements in neurophysiological outcomes, both local to the wrist (i.e. median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 cortical separation distance). Moreover, greater improvement in second/third interdigit cortical separation distance following verum acupuncture predicted sustained improvements in symptom severity at 3-month follow-up. We further explored potential differential mechanisms of local versus distal acupuncture using diffusion tensor imaging of white matter microstructure adjacent to the primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 49.7 AE 9.9 years old), patients with carpal tunnel syndrome demonstrated increased fractional anisotropy in several regions and, for these regions we found that improvement in median nerve latency was associated with reduction of fractional anisotropy near (i) contralesional hand area following verum, but not sham, acupuncture; (ii) ipsilesional hand area following local, but not distal or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not local or sham, acupuncture. As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex ...

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“…1 Since the discharge is not complete, the charge at the electrode accumulates, and the residual charge at the end of the n-th discharge phase will be depending on the residual charge of the previous phase:…”

Section: A Quasi-static Electrode Voltagementioning

confidence: 99%

“…A large number of possible applications from disease ailments [1] to prosthetics [2] are now investigated. Over the years, various modes of stimulation (current, voltage or charge) have been analyzed in literature and sophisticated circuits have been developed for precise charge balancing.…”

Section: Introductionmentioning

confidence: 99%

Analysis of passive charge balancing for safe current-mode neural stimulation

Rueda

Ballini

Hellepute

et al. 2017

2017 IEEE International Symposium on Circuits and Systems (ISCAS)

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Abstract-Charge balancing has been often considered as one of the most critical requirement for neural stimulation circuits. Over the years several solutions have been proposed to precisely balance the charge transferred to the tissue during anodic and cathodic phases. Elaborate dynamic current sources/sinks with improved matching, and feedback loops have been proposed with a penalty on circuit complexity, area or power consumption. Here we review the dominant assumptions in safe stimulation protocols, and derive mathematical models to determine the effectiveness of passive charge balancing in a typical application scenario.

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A jump-start for electroceuticals

Cited by 503 publications

References 10 publications

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture

Analysis of passive charge balancing for safe current-mode neural stimulation

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