Bypassing Opioid Receptors for Safer Analgesia: direct activation of downstream TREK1 channels – BORSA

We have shown that the TREK1 potassium channel is involved in the analgesic effect of morphine but not in its adverse effects, and that direct activation of this channel is analgesic and well tolerated. Based on the recent development of new TREK1 activators, this project aims to (1) determine in which pathological pain conditions this strategy is the most effective, (2) define whether this analgesic effect involves TREK1 channels of the central and/or peripheral nervous system to guide the development of future compounds, and (3) investigate potential adverse effects triggered by TREK1 activation, especially at the central level. This work aims towards a better understanding of the pathophysiological mechanisms of pain, the analgesic potential of TREK1 activators as well as the safety of this strategy. TREK1 channel activators could indeed offer an alternative to opioids and constitute a new class of effective and better tolerated painkillers.