Evidence map›Paper›PMID 37037361›Full record

ArticleBrain, behavior, and immunity2023

Intrathecal non-viral interleukin-10 gene therapy ameliorates neuropathic pain as measured by both classical static allodynia and a novel supra-spinally mediated pain assay, the Two-Arm Rodent Somatosensory (TARS) task.

M A Clements, A J Kwilasz, S T Litwiler, Z Sents, B J Woodall, K Hayashida, L R Watkins

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

Article in Brain, behavior, and immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

M A ClementsDepartment of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
A J KwilaszDepartment of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
S T LitwilerDepartment of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
Z SentsDepartment of Engineering, University of Colorado - Boulder, Boulder, CO, USA.
B J WoodallDepartment of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA.
K HayashidaPharmacology Department, Shin Nippon Biomedical Laboratories, Ld., Kagoshima, Japan.
L R WatkinsDepartment of Psychology and Neuroscience, University of Colorado - Boulder, Boulder, CO, USA. Electronic address: linda.watkins@colorado.edu.
University of Colorado Boulder · USShin Nippon Biomedical Laboratories (Japan) · JP

Funding

Enduring enhancement of neuropathic pain by early post-trauma morphineR01DA044934 · NIDA · UNIVERSITY OF COLORADO · PI WATKINS, LINDA · 2018 to 2022
$2.7M
Preventing Transition of Acute-to-Chronic Neuropathic Pain: Models, Mechanisms &R01DE021966 · NIDCR · UNIVERSITY OF COLORADO · PI BARTH, DANIEL S., FLESHNER, MONIKA · 2011 to 2015
$2.0M
Targeting neuropathic pain prevention: Modulating the neuroimmunology of peripheral nerve injuryR01AT009366 · NCCIH · UNIVERSITY OF COLORADO · PI WATKINS, LINDA · 2017 to 2021
$1.7M
Targeting toll like receptor 4 (TLR4) and TLR2 to resolve EAE-associated paralysis, pain and cognitive deficits: efficacy of a clinically-relevant blood brain barrier permeable TLR4/TLR2 antagonistR01NS097313 · NINDS · UNIVERSITY OF COLORADO · PI WATKINS, LINDA · 2016 to 2020
$1.7M
NCCIH NIH HHS R01 AT009366NIDA NIH HHS R01 DA044934NIDCR NIH HHS R01 DE021966NINDS NIH HHS R01 NS097313
6 · The paper itself

Abstract

Intrathecal delivery of interleukin-10 (IL-10) gene therapy has been reported to be effective in suppressing pain enhancement in a variety of rodent models. However, all publications that have tested this treatment have relied upon measures of static allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test). As this plasmid DNA IL-10 (pDNA-IL10) therapeutic approach is now in human clinical trials for multiple pain indications, including intrathecal delivery for human neuropathic pain, it is important to consider the recent concerns raised in the pain field that such tests reflect spinal rather than supraspinal processing of, and responsivity to, noxious stimuli. Consequently, this raises the question of whether intrathecal pDNA-IL10 can reverse established neuropathic pain when assessed by a test requiring supraspinal, rather than solely spinal, mediation of the behavioral response. The present study utilizes the rat sciatic chronic constriction injury (CCI) model of neuropathic pain to compare the expression of static allodynia with that of cognitively controlled choice behavior in a two-arm maze, adapted from Hayashida et al. (2019). This modification, termed the Two-Arm Rodent Somatosensory (TARS) task, provides rats free choice to reach a desired goal box via a short "arm" of the maze with tactile probes as flooring versus a longer "arm" of the maze with a smooth surface. Here we demonstrate that static allodynia and avoidance of the nociceptive flooring in TARS develop in parallel over time, and that both behaviors also resolve in parallel following intrathecal pDNA-IL10 gene therapy. Details for the construction and use of this new maze design are also provided. Together, this study documents both: (a) the important finding that intrathecal IL-10 gene therapy does indeed resolve neuropathic pain as measured by a supraspinally-mediated behavioral task, and (b) a new, supraspinally-mediated task that allows behavioral assessments across weeks and allows the analysis of both development and resolution of neuropathic pain by therapeutic interventions. As such, the TARS operant behavior task is an improvement over other approaches such as the mechanical conflict-avoidance system which have difficulties demonstrating development and reversal of pain behavior in a within-subject design.

Indexed as

HyperalgesiaNeuralgiaDNAGenetic TherapyHumansInterleukin-10DNAInterleukin-10AllodyniaChronic constriction injuryMaze learningOperant taskRats

Identifiers

PMID37037361
PMCPMC10330316
OpenAlexW4362717341

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.