Evidence map›Paper›PMID 36243579›Full record

ArticleBritish journal of anaesthesia2022

The nonopioid cholinergic agonist GTS-21 mitigates morphine-induced aggravation of burn injury pain together with inhibition of spinal microglia activation in young rats.

Yang Ren, Yinhui Zhou, Zerong You, Hao Deng, William R Kem, Jianren Mao, Wei Zhang, J A Jeevendra Martyn

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of anaesthesia, 2022. 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
1.2field-weighted citation impact, top 21% 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, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Pathophysiology and management of burn injury-induced pain.Burns open : an international open access journal for burn injuries · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
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

8 authors at 4 institutions in 2 countries.

Yang RenDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Shriners Hospital for Children - Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Anaesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: jmartyn@mgh.harvard.edu.
Yinhui ZhouDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Shriners Hospital for Children - Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Anaesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zerong YouDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Hao DengDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
William R KemDepartment of Pharmacology, University of Florida, Gainesville, FL USA.
Jianren MaoDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Wei ZhangDepartment of Anaesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J A Jeevendra MartynDepartment of Anaesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; Shriners Hospital for Children - Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Harvard University · USShriners Hospitals for Children - Erie · USFirst Affiliated Hospital of Zhengzhou University · CNUniversity of Florida · US

Funding

Major Burn Injury and its Effects on Acute and Superimposed Surgical PainR01GM142042 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MARTYN, JEEVENDRA · 2020 to 2023
$1.3M
NIGMS NIH HHS R01 GM142042
6 · The paper itself

Abstract

backgroundRepetitive opioid use does not always alleviate basal pain, procedural pain, or both after burn injury. Mitigation of burn injury-site pain can be achieved by GTS-21 stimulation of α7-acetylcholine nicotinic receptors (α7AChRs) and reduced microglia activation in rat. We tested the hypothesis that morphine exaggerates burn injury-site pain and GTS-21 alleviates both morphine-induced aggravated burn injury pain and microglia activation.

methodsYoung rats with dorsal paw burn injury or sham-burn received intraperitoneal saline, morphine, GTS-21, or a combination twice daily for 14 days. Ipsilateral plantar pain thresholds were tested every other day before morning drugs from days 0-20. Spinal microglia activation, evidenced as pain-transducer (tumour necrosis factor-α [TNF-α], interleukin [IL]-6, IL-1β, nuclear factor kappa B [NF-κB], Toll-like receptor 4 [TLR4]) expression, was examined using immunohistochemistry and immunoblot. In cultured microglia, morphine-induced cytokine expression was measured (quantitative polymerase chain reaction/enzyme-linked immunosorbent assay [qPCR/ELISA]).

resultsMorphine aggravated allodynia at day 5 in sham-burn (P=0.039, n=8-11) but significantly aggravated burn injury site allodynia by day 3 (P=0.010, n=8-11). Microgliosis paralleled nociceptive behaviour changes where burn injury with morphine had highest microgliosis compared with burn injury, morphine alone, or controls (number of cells per field [SD]: 33.8 [2.4], 18.0 [4.1], 8.2 [1.9], and 4.8 [2.0], respectively; P<0.001, n=4-5]. GTS-21 reversed the morphine-induced pain component in sham-burn and burn injury rats together with reduced microgliosis and spinal pain-transducer expression (TNF-α, IL-6, IL-1β, NF-κB, and TLR4). Morphine-exposed microglial cells showed increased cytokine expression, which was mitigated by GTS-21.

conclusionsMorphine or burn injury alone increases pain together with microgliosis and pain-transducer expression. Morphine administration augments burn injury-site nociception sooner and aggravated spinal microgliosis and inflammatory pain-transducer expression. GTS-21 has the potential to treat morphine-induced pain in burn injury.

Indexed as

BurnsMorphinealpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzylidene CompoundsCholinergic AgonistsHyperalgesiaMicrogliaNF-kappa BPainPyridinesRatsRats, Sprague-DawleySpinal CordToll-Like Receptor 4Tumor Necrosis Factor-alpha3-(2,4-dimethoxybenzylidene)anabaseinealpha7 Nicotinic Acetylcholine ReceptorBenzylidene CompoundsCholinergic AgonistsMorphineNF-kappa BPyridinesToll-Like Receptor 4Tumor Necrosis Factor-alphaallodyniaantinociceptionburnhyperalgesiamicrogliamorphineneuroinflammationopioids

Identifiers

PMID36243579
PMCPMC13169034
OpenAlexW4304891728

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.