TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol

David A Andersson, Clive Gentry, Lisa Alenmyr, Dan Killander, Simon E Lewis, Anders Andersson, Bernard Bucher, Jean-Luc Galzi, Olov Sterner, Stuart Bevan (), Edward D Högestätt () and Peter M Zygmunt
Additional contact information
David A Andersson: King's College London, Wolfson Centre for Age-Related Diseases,
Clive Gentry: King's College London, Wolfson Centre for Age-Related Diseases,
Lisa Alenmyr: Lund University, Skåne University Hospital
Dan Killander: Centre for Analysis and Synthesis Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Simon E Lewis: 1 South, University of Bath, Bath BA2 7AY, UK.
Anders Andersson: Lund University, Skåne University Hospital
Bernard Bucher: UMR 7213, CNRS/Université de Strasbourg, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France.
Jean-Luc Galzi: Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant
Olov Sterner: Centre for Analysis and Synthesis Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Stuart Bevan: King's College London, Wolfson Centre for Age-Related Diseases,
Edward D Högestätt: Lund University, Skåne University Hospital
Peter M Zygmunt: Lund University, Skåne University Hospital

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: Abstract TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1−/− mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, activate mouse and human TRPA1. These metabolites also activate native TRPA1 and, as a consequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons. The N-acetyl-p-benzoquinoneimine metabolite L-cysteinyl-S-acetaminophen was detected in the mouse spinal cord after systemic acetaminophen administration. In the hot-plate test, intrathecal administration of N-acetyl-p-benzoquinoneimine, p-benzoquinone and the electrophilic TRPA1 activator cinnamaldehyde produced antinociception that was lost in Trpa1−/− mice. Intrathecal injection of a non-electrophilic cannabinoid, Δ9-tetrahydrocannabiorcol, also produced TRPA1-dependent antinociception in this test. Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/ncomms1559 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1559

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1559

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().