Le canal potassique TREK-1 : une cible moléculaire d'intérêt pour le développement d'antalgiques efficaces et bien tolérés

Morphine, the gold standard pain reliever for severe acute or chronic nociceptive pain, suffers from invalidating adverse effects, which can alter quality of life of patients and in some rare cases jeopardize the vital prognosis. Unfortunately, morphine elicits both therapeutic and adverse effects, primarily through the same mu opioid receptor, which makes it difficult to separate the two types of effects. We recently showed that beneficial and deleterious effects of morphine are mediated through different signaling pathways downstream from mu opioid receptor. The TREK-1 potassium channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence, three main adverse effects of opioid analgesic therapy. These results suggest that direct activation of the TREK-1 channel, acting downstream from the mu opioid receptor, might have strong analgesic effects without opioids-like adverse effects. Ligands for these channels, which are either marketed drugs for other indications or novel synthetized compounds are currently in development in the Analgesia Institute we have recently created.