Evidence map›Paper›PMID 35524407›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022

Precision spinal gene delivery-induced functional switch in nociceptive neurons reverses neuropathic pain.

Takahiro Tadokoro, Mariana Bravo-Hernandez, Kirill Agashkov, Yoshiomi Kobayashi, Oleksandr Platoshyn, Michael Navarro, Silvia Marsala, Atsushi Miyanohara, Tetsuya Yoshizumi, Michiko Shigyo and 20 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 15 citations in OpenAlex.

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  6. Efficient genetic perturbation of murine sensory neuronsbioRxiv : the preprint server for biology · 2025
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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

30 authors at 8 institutions in 6 countries.

Takahiro TadokoroNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA; Department of Anesthesiology, University of Ryukyus, Okinawa, Japan; Neurgain Technologies, 9620 Towne Centre Drive, Suite 100, San Diego, CA 92121, USA.
Mariana Bravo-HernandezNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Kirill AgashkovDepartments of Sensory Signaling and Molecular Biophysics, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
Yoshiomi KobayashiNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Oleksandr PlatoshynNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Michael NavarroNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Silvia MarsalaNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA; Neurgain Technologies, 9620 Towne Centre Drive, Suite 100, San Diego, CA 92121, USA.
Atsushi MiyanoharaNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA; Vector Core Laboratory, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Tetsuya YoshizumiNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Michiko ShigyoNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Volodymyr KrotovDepartments of Sensory Signaling and Molecular Biophysics, Bogomoletz Institute of Physiology, Kyiv, Ukraine.
Stefan JuhasInstitute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, Czech Republic.
Jana JuhasovaInstitute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, Czech Republic.
Duong NguyenInstitute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, Czech Republic.
Helena Kupcova SkalnikovaInstitute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, Czech Republic.
Jan MotlikInstitute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, Czech Republic.
Hana StudenovskaInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Department of Biomaterials and Bioanalogous Systems, Heyrovsky Square 2,162 06 Prague 6, Czech Republic.
Vladimir ProksInstitute of Macromolecular Chemistry, Czech Academy of Sciences, Department of Biomaterials and Bioanalogous Systems, Heyrovsky Square 2,162 06 Prague 6, Czech Republic.
Rajiv ReddyDepartment of Anesthesiology, Pain Medicine, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Shawn P DriscollGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Thomas D GlennGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Taratorn KemthongNational Primate Research Center of Thailand, Chulalongkorn University, Kaengkhoi District, Saraburi 18110, Thailand.
Suchinda MalaivijitnondNational Primate Research Center of Thailand, Chulalongkorn University, Kaengkhoi District, Saraburi 18110, Thailand.
Zoltan TomoriDepartment of Biophysics, Institute of Experimental Physics, Slovak Academy of Sciences, Kosice, Slovakia.
Ivo VanickyInstitute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Kosice, Slovakia.
Manabu KakinohanaDepartment of Anesthesiology, University of Ryukyus, Okinawa, Japan.
Samuel L PfaffGene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Joseph CiacciDepartment of Neurosurgery, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
Pavel BelanDepartments of Sensory Signaling and Molecular Biophysics, Bogomoletz Institute of Physiology, Kyiv, Ukraine; Kyiv Academic University, Kyiv, Ukraine.
Martin MarsalaNeuroregeneration Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA; Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Kosice, Slovakia. Electronic address: mmarsala@ucsd.edu.
University of California San Diego · USCzech Academy of Sciences, Institute of Animal Physiology and Genetics · CZBogomoletz Institute of Physiology · UASalk Institute for Biological Studies · USSlovak Academy of Sciences · SKChulalongkorn University · THCzech Academy of Sciences, Institute of Macromolecular Chemistry · CZUniversity of the Ryukyus · JP

Funding

Spinal Circuits for the Control of Dextrous MovementU19NS112959 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI PFAFF, SAMUEL L. · 2019 to 2023
$14.3M
Characterization of spinal circuits underlying motor synergy functionR01NS123160 · NINDS · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI PFAFF, SAMUEL L. · 2021 to 2025
$3.0M
The Role of the Complement System in Spinal Mechanisms of Chronic PainR01NS113189 · NINDS · UNIVERSITY OF IOWA · PI USACHEV, YURIY M · 2019 to 2023
$2.2M
NINDS NIH HHS R01 NS113189NINDS NIH HHS R01 NS123160NINDS NIH HHS U19 NS112959
6 · The paper itself

Abstract

Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously induced change in developmentally imprinted excitatory neurotransmitter phenotypes of these neurons to inhibitory has not yet been achieved. Here, we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-aminobutyric acid) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) that persisted for a minimum of 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (e.g., sedation, motor weakness, loss of normal sensation) were seen between 2 and 13 months post-treatment in naive adult mice, pigs, and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord or peripheral nerve injury-induced neuropathic pain.

Indexed as

NeuralgiaNociceptorsAnimalsGene Transfer TechniquesMicePosterior Horn CellsSpinal CordSpinal Cord Dorsal HornSwineGAD65 and VGATlong-lasting pain reversalneuropathic painprecision spinal vector deliverysubpial injection techniquesubpial non-human primatessubpial pigtargeted AAV9 delivery

Identifiers

PMID35524407
PMCPMC9372322
OpenAlexW4229064322

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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.