New vistas in opioid control of pain

► Multiple μ-opioid receptors (splice variants) are involved in the antinociception induced by μ-opioid receptor agonists. ► Atypical μ-opioid receptors (specific splice variants) may be involved in the distinct antinociceptive profile of discrete agonists. ► Atypical μ-opioid receptors may be involved in the lack of rewarding effect of some μ-opioid receptor agonists. ► μ-Opioid receptor agonists specific for atypical μ-opioid receptors may be effective against morphine-resistant interactive pain. ► Atypical μ-opioid receptors may be the target molecule to produce analgesics better than morphine.