Evidence map›Paper›PMID 22722575›Full record

ArticleAnesthesiology2012

Ondansetron reverses antihypersensitivity from clonidine in rats after peripheral nerve injury: role of γ-aminobutyric acid in α2-adrenoceptor and 5-HT3 serotonin receptor analgesia.

Ken-ichiro Hayashida, Masafumi Kimura, Masaru Yoshizumi, Shotaro Hobo, Hideaki Obata, James C Eisenach

Open access · bronzeAbstract read
In one paragraph

Article in Anesthesiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

9 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. FOXD3-mediated transactivation of ALKBH5 promotes neuropathic pain via mProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Article
  4. Baicalin relieves neuropathic pain by regulating αExperimental and therapeutic medicine · 2020
    Article
  5. Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018
    Article
  6. Article
  7. Article
  8. Article
  9. Melanocortin-4 receptor expression in the rostral ventromedial medulla involved in modulation of nociception in transgenic mice.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2013
    Article
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

6 authors at 2 institutions in 2 countries.

Ken-ichiro HayashidaWake Forest University School of Medicine, Winston Salem, NC, USA.
Masafumi Kimura
Masaru Yoshizumi
Shotaro Hobo
Hideaki Obata
James C Eisenach
Gunma University · JPWake Forest University · US

Funding

Spinal Noradrenergic Sprouting after Nerve InjuryR01NS057594 · NINDS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI EISENACH, JAMES · 2008 to 2012
$1.7M
Mechanisms and Consequences of Locus Coeruleus ActivationR01DA027690 · NIDA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HAYASHIDA, KENICHIRO · 2010 to 2014
$1.4M
NIDA NIH HHS DA27690NIDA NIH HHS R01 DA027690NINDS NIH HHS NS57594NINDS NIH HHS R01 NS057594
6 · The paper itself

Abstract

introductionMonoaminergic pathways, impinging an α2-adrenoceptors and 5-HT3 serotonin receptors, modulate nociceptive transmission, but their mechanisms and interactions after neuropathic injury are unknown. Here we examine these interactions in rodents after nerve injury.

methodsMale Sprague-Dawley rats following L5-L6 spinal nerve ligation (SNL) were used for either behavioral testing, in vivo microdialysis for γ-aminobutyric acid (GABA) and acetylcholine release, or synaptosome preparation for GABA release.

resultsIntrathecal administration of the α2-adrenoceptor agonist (clonidine) and 5-HT3 receptor agonist (chlorophenylbiguanide) reduced hypersensitivity in SNL rats via GABA receptor-mediated mechanisms. Clonidine increased GABA and acetylcholine release in vivo in the spinal cord of SNL rats but not in normal rats. Clonidine-induced spinal GABA release in SNL rats was blocked by α2-adrenergic and nicotinic cholinergic antagonists. The 5-HT3 receptor antagonist ondansetron decreased and chlorophenylbiguanide increased spinal GABA release in both normal and SNL rats. In synaptosomes from the spinal dorsal horn of SNL rats, presynaptic GABA release was increased by nicotinic agonists and decreased by muscarinic and α2-adrenergic agonists. Spinally administered ondansetron significantly reduced clonidine-induced antihypersensitivity and spinal GABA release in SNL rats.

conclusionThese results suggest that spinal GABA contributes to antihypersensitivity from intrathecal α2-adrenergic and 5-HT3 receptor agonists in the neuropathic pain state, that cholinergic neuroplasticity after nerve injury is critical for α2-adrenoceptor-mediated GABA release, and that blockade of spinal 5-HT3 receptors reduces α2-adrenoceptor-mediated antihypersensitivity via reducing total GABA release.

Indexed as

Peripheral Nerve InjuriesAdrenergic alpha-2 Receptor AgonistsAnalgesiaAnimalsClonidineDisease Models, Animalgamma-Aminobutyric AcidMaleOndansetronPainPain ManagementRatsRats, Sprague-DawleyReceptors, Adrenergic, alpha-2Receptors, Serotonin, 5-HT3Serotonin AntagonistsAdrenergic alpha-2 Receptor AgonistsClonidinegamma-Aminobutyric AcidOndansetronReceptors, Adrenergic, alpha-2Receptors, Serotonin, 5-HT3Serotonin Antagonists

Identifiers

PMID22722575
PMCPMC3496934
OpenAlexW2159289581

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.