Evidence map›Paper›PMID 27589093›Full record

ArticlePain2016

Activation of cannabinoid CB1 receptor contributes to suppression of spinal nociceptive transmission and inhibition of mechanical hypersensitivity by Aβ-fiber stimulation.

Fei Yang, Qian Xu, Bin Shu, Vinod Tiwari, Shao-Qiu He, Louis P Vera-Portocarrero, Xinzhong Dong, Bengt Linderoth, Srinivasa N Raja, Yun Wang and 1 more

Open access · greenAbstract read
In one paragraph

Article in Pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 69 citations in OpenAlex.

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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

11 authors at 5 institutions in 3 countries.

Fei YangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qian XuThe Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bin ShuDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Vinod TiwariDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Shao-Qiu HeDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Louis P Vera-PortocarreroNeuromodulation Research, Medtronic Inc., Minneapolis, MN, USA.
Xinzhong DongThe Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bengt LinderothDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Srinivasa N RajaDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yun WangDepartment of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
Yun GuanDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins Medicine · USJohns Hopkins University · USCapital Medical University · CNKarolinska Institutet · SEMedtronic (United States) · US

Funding

INJURY-INDUCES PAIN-- CHEMICAL MODULATION OF NOCICEPTORSR01NS026363 · NINDS · JOHNS HOPKINS UNIVERSITY · PI RAJA, SRINIVASA N. · 1989 to 2021
$6.8M
Mrgs as New Target for the Treatment of Neuropathic PainR01NS070814 · NINDS · JOHNS HOPKINS UNIVERSITY · PI GUAN, YUN · 2011 to 2020
$3.2M
Howard Hughes Medical InstituteNINDS NIH HHS R01 NS026363NINDS NIH HHS R01 NS070814
6 · The paper itself

Abstract

Activation of Aβ-fibers is an intrinsic feature of spinal cord stimulation (SCS) pain therapy. Cannabinoid receptor type 1 (CB1) is important to neuronal plasticity and pain modulation, but its role in SCS-induced pain inhibition remains unclear. In this study, we showed that CB1 receptors are expressed in both excitatory and inhibitory interneurons in substantia gelatinosa (SG). Patch-clamp recording of the evoked excitatory postsynaptic currents (eEPSCs) in mice after spinal nerve ligation (SNL) showed that electrical stimulation of Aβ-fibers (Aβ-ES) using clinical SCS-like parameters (50 Hz, 0.2 millisecond, 10 μA) induced prolonged depression of eEPSCs to C-fiber inputs in SG neurons. Pretreatment with CB1 receptor antagonist AM251 (2 μM) reduced the inhibition of C-eEPSCs by Aβ-ES in both excitatory and inhibitory SG neurons. We further determined the net effect of Aβ-ES on spinal nociceptive transmission in vivo by recording spinal local field potential in SNL rats. Epidural SCS (50 Hz, Aβ-plateau, 5 minutes) attenuated C-fiber-evoked local field potential. This effect of SCS was partially reduced by spinal topical application of AM251 (25 μg, 50 μL), but not CB2 receptor antagonist AM630 (100 μg). Finally, intrathecal pretreatment with AM251 (50 μg, 15 μL) in SNL rats blocked the inhibition of behavioral mechanical hypersensitivity by SCS (50 Hz, 0.2 millisecond; 80% of motor threshold, 60 minutes). Our findings suggest that activation of spinal CB1 receptors may contribute to synaptic depression to high-threshold afferent inputs in SG neurons after Aβ-ES and may be involved in SCS-induced inhibition of spinal nociceptive transmission after nerve injury.

Indexed as

AnimalsCannabinoid Receptor AgonistsDisease Models, AnimalFemaleGlutamate DecarboxylaseHyperalgesiaLigationLuminescent ProteinsMaleMembrane PotentialsMiceMice, TransgenicNerve Fibers, MyelinatedNeuralgiaNociceptorsPosterior Horn CellsCannabinoid Receptor AgonistsGlutamate Decarboxylaseglutamate decarboxylase 1Luminescent ProteinsReceptor, Cannabinoid, CB1Slc17a6 protein, mouseVesicular Glutamate Transport Protein 2

Identifiers

PMID27589093
PMCPMC5069149
OpenAlexW2500014247

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.