Paracetamol pain relief works via TRPA1

Paracetamol metabolites and a particular cannabinoid activate a channel protein called TRPA1 to mediate pain relief. This finding, reported in Nature Communications this week, suggests that identification of other agents that activate this channel may be useful analgesics. Using mice that lack TRPA1, Edward Hogestatt and colleagues demonstrated that this protein is required to mediate the analgesic properties of acetaminophenl, also known as paracetmaol. The authors showed that the metabolites of paracetamol activate the channel, and they could identify the presence of one of these metabolites in the mouse spinal cord, suggesting that this is the site of TRPA1 activation that is responsible for pain relief. They demonstrated that a cannabinoid derivative, Δ9-tetrahydrocannabiorcol which is known to activate TRPA1, also had an analgesic effect in the mouse, suggesting that the use of this compound or other agents that do not cause toxicity like paracetamol, may be useful for the treatment of pain.