Evidence map›Paper›PMID 36402658›Full record

ArticleNeuromodulation : journal of the International Neuromodulation Society2023

Steering Toward Normative Wide-Dynamic-Range Neuron Activity in Nerve-Injured Rats With Closed-Loop Peripheral Nerve Stimulation.

Christine Beauchene, Claire A Zurn, Daniel Ehrens, Irina Duff, Wanru Duan, Michael Caterina, Yun Guan, Sridevi V Sarma

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuromodulation : journal of the International Neuromodulation Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Hydrogel-based neural engineering for skin wound healing.Frontiers in cell and developmental biology · 2026
    Review
  4. Review
  5. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Christine BeaucheneDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: cbeauch2@jhu.edu.
Claire A ZurnDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA.
Daniel EhrensDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA.
Irina DuffDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Wanru DuanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael CaterinaDepartment of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yun GuanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sridevi V SarmaDepartment of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ssarma2@jhmi.edu.
Johns Hopkins University · US

Funding

Interdisciplinary Training in Biobehavioral Pain ResearchT32NS070201 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DONG, XINZHONG, SMITH, MICHAEL T · 2010 to 2024
$3.6M
Birth Tissue Products for Non-opioid Treatment of Post-surgical PainR01NS117761 · NINDS · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN · 2020 to 2024
$2.6M
ASPIRE - A Joint Johns Hopkins, Morgan State and Coppin State IRACDA ProgramK12GM123914 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BROWN, LISA D., SARMA, SRIDEVI V. · 2018 to 2022
$2.5M
Mechanistic Study of Pain Inhibition by Activation of Non-nociceptive Afferent FibersR01NS110598 · NINDS · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN · 2019 to 2024
$2.4M
CRCNS: Computational Model of Chronic Pain Analgesia via Closed-Loop Peripheral Nerve StimulationR01AT011844 · NCCIH · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN, SARMA, SRIDEVI V. · 2021 to 2025
$1.9M
CRCNS: Towards Pain Control: Synergizing Computational and Biological ApproachesR01AT009401 · NCCIH · JOHNS HOPKINS UNIVERSITY · PI SARMA, SRIDEVI V. · 2016 to 2019
$1.6M
Pre-Doctoral Training Program in Computational MedicineT32GM119998 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI MAC GABHANN, FEILIM C · 2017 to 2021
$1.5M
NCCIH NIH HHS R01 AT009401NCCIH NIH HHS R01 AT011844NIGMS NIH HHS K12 GM123914NIGMS NIH HHS T32 GM119998NINDS NIH HHS R01 NS110598NINDS NIH HHS R01 NS117761NINDS NIH HHS T32 NS070201
6 · The paper itself

Abstract

objectivesChronic pain is primarily treated with pharmaceuticals, but the effects remain unsatisfactory. A promising alternative therapy is peripheral nerve stimulation (PNS), but it has been associated with suboptimal efficacy because its modulation mechanisms are not clear and the current therapies are primarily open loop (ie, manually adjusting the stimulation parameters). In this study, we developed a proof-of-concept computational modeling as the first step toward implementing closed-loop PNS in future biological studies. When developing new pain therapies, a useful pain biomarker is the wide-dynamic-range (WDR) neuron activity in the dorsal horn. In healthy animals, the WDR neuron activity occurs in a stereotyped manner; however, this response profile can vary widely after nerve injury to create a chronic pain condition. We hypothesized that if injury-induced changes of neuronal response can be normalized to resemble those of a healthy condition, the pathological aspects of pain may be treated while maintaining protective physiological nociception. MATERIALS AND

methodsUsing an in vivo electrophysiology data set of WDR neuron recordings obtained in nerve-injured rats and naïve rats, we constructed sets of linear phenomenologic models of WDR firing rate during windup stimulation for both conditions. Then, we applied robust control systems techniques to identify a closed-loop PNS controller, which can drive the dynamics of WDR neuron response in neuropathic pain model into ranges associated with normal physiological pain.

resultsThe sets of identified linear models can accurately predict, in silico, nonlinear neural responses to electrical stimulation of the peripheral nerve. In addition, we showed that continuous closed-loop control of PNS can be used to normalize WDR neuron firing responses in three injured cases.

conclusionsIn this proof-of-concept study, we show how tractable, linear mathematical models of pain-related neurotransmission can be used to inform the development of closed-loop PNS. This new application of robust control to neurotechnology may also be expanded and applied across other neuromodulation applications.

Indexed as

Chronic PainNeuralgiaTranscutaneous Electric Nerve StimulationAnimalsNeuronsPeripheral NervesRatsChronic painmodel matchingperipheral nerve stimulationrobust controlwide-dynamic-range neuron

Identifiers

PMID36402658
PMCPMC10081946
OpenAlexW4309436506

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.