Blockade of adrenomedullin receptors reverses morphine tolerance and its neurochemical mechanisms

► Acute administration of AM receptor antagonist AM22-52 resumed potency of morphine. ► The AM22-52 treatment suppressed morphine tolerance-associated hyperalgesia. ► AM22-52 reversed morphine induced-enhancement of nNOS and CGRP in spinal dorsal horn and dorsal root ganglia. ► The first study to show association of endogenous opioid peptide with morphine potency.