Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey.

Clicks: 336
ID: 95770
2019
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #12 of 36 articles by views in british journal of pharmacology

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide) to activate CB receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms supporting paracetamol-induced analgesia remain unknown.The effects of paracetamol on brain function in Sprague-Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo H-NMR and microdialysis. Analgesic effects of paracetamol were assessed by behavioural tests and challenged with different inhibitors, administered systemically or microinjected in the PAG.Paracetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel-mGlu receptor-PLC-DAGL-CB receptor signalling cascade to exert its analgesic effects.The elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.
Reference Key
barrire2019paracetamolbritish Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Barrière, David André;Boumezbeur, Fawzi;Dalmann, Romain;Cadeddu, Roberto;Richard, Damien;Pinguet, Jérémy;Daulhac, Laurence;Sarret, Philippe;Whittingstall, Kevin;Keller, Matthieu;Mériaux, Sébastien;Eschalier, Alain;Mallet, Christophe;
Journal british journal of pharmacology
Year 2019
DOI
10.1111/bph.14934
URL
Keywords
sba-15 nanostructured silica 3 analgesia 5 crotoxin 2 hypernociception 6 neuropathic pain 1 partial sciatic nerve ligation 4

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.