Evidence map›Paper›PMID 30348772›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.

Yi-Hung Chen, Hsin-Jung Lee, Ming Tatt Lee, Ya-Ting Wu, Yen-Hsien Lee, Ling-Ling Hwang, Ming-Shiu Hung, Andreas Zimmer, Ken Mackie, Lih-Chu Chiou

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
3.6field-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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 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

10 authors at 7 institutions in 4 countries.

Yi-Hung ChenGraduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan 40402.
Hsin-Jung LeeDepartment of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan 10051.
Ming Tatt LeeDepartment of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan 10051.
Ya-Ting WuGraduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan 40402.
Yen-Hsien LeeGraduate Institute of Biomedical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan 110.
Ling-Ling HwangGraduate Institute of Biomedical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan 110.
Ming-Shiu HungInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan 35053.
Andreas ZimmerInstitute for Molecular Psychiatry, University of Bonn, 53113 Bonn, Germany.
Ken MackieGill Center for Biomolecular Research, Indiana University, Bloomington, IN 47405.
Lih-Chu ChiouGraduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan 40402; lcchiou@ntu.edu.tw.
National Taiwan University · TWTaipei Medical University · TWAsia University · TWChina Medical University · TWIndiana University Bloomington · USNational Health Research Institutes · TWUniversity of Bonn · DE

Funding

Neuronal cannabinoidsR01DA011322 · NIDA · UNIVERSITY OF WASHINGTON · PI MACKIE, KENNETH · 1998 to 2014
$3.4M
Cannabinoid Modulation of Cell FunctionK05DA021696 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI MACKIE, KENNETH · 2007 to 2017
$1.3M
NIDA NIH HHS K05 DA021696NIDA NIH HHS R01 DA011322
6 · The paper itself

Abstract

Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in

Indexed as

AnalgesiaAnimalsEndocannabinoidsGray MatterHumansMedian NerveMiceOrexinsEndocannabinoidsOrexinsanalgesiaendocannabinoidmedian nerve stimulationorexinperiaqueductal gray

Identifiers

PMID30348772
PMCPMC6233149
OpenAlexW2897151902

What OpenQuestion holds

Textmetadata
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.