Activities per year
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.
Original language | English |
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Article number | 551 |
Journal | Nature Communications |
Volume | 2 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2011 |
Fingerprint
Dive into the research topics of 'TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol'. Together they form a unique fingerprint.Activities
- 3 Types of Public engagement and outreach - Media article or participation
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New Scientist, Article on Paracetamol
Andersson, D. (Interviewee)
Jun 2014Activity: Other › Types of Public engagement and outreach - Media article or participation
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Research Highlight
Andersson, D. (Interviewee)
16 Dec 2011Activity: Other › Types of Public engagement and outreach - Media article or participation
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Publication Highlight
Andersson, D. (Interviewee)
14 Dec 2011Activity: Other › Types of Public engagement and outreach - Media article or participation
Prizes
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King’s College London/London Law Trust Medal Fellowship
Andersson, D. (Recipient), 2009
Prize: Prize (including medals and awards)