Grant: Project Grant

Despite the existence of a multitude of drugs with analgesic properties, the treatment of pain often remains problematic. Notwithstanding significant side effects (constipation, nausea, sedation), alkaloid compounds remain the most effective drugs to relieve chronic pain. The best known of all alkaloids undoubtedly remains morphine, belonging to the family of opiates. Morphine and its derivatives bind and activate at least three subtypes of G protein-coupled receptors, the mu (MOP), delta (DOP) and kappa (KOP) opioid receptors. Although these three receptor subtypes possess analgesic properties, the actions of the majority of opioids used clinically target MOP. In contrast to the latter, activation of DOP leads to few unwanted effects. Under normal conditions (i.e. in healthy animals), the analgesic potency of delta selective agonists is lower than that of morphine. In recent years, however, it has been shown that under certain conditions, the activation of DOP can counter the painful sensations with an efficacy close to morphine. In my laboratory we are interested in studying the mechanisms regulating the trafficking of DOP toward the plasma membrane of nociceptive neurons under conditions of chronic pain. A better understanding of these mechanisms could help develop strategies to increase the effectiveness of pain therapies and thus improve the quality of life of patients.