alpha 2 delta-1-Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

摘要

Background: Chronic use of mu-opioid receptor agonists paradoxically causes both hyperalgesia and the loss of analgesic efficacy. Opioid treatment increases presynaptic N-methyl-d-aspartate receptor activity to potentiate nociceptive input to spinal dorsal horn neurons. However, the mechanism responsible for this opioid- induced activation of presynaptic N-methyl-d-aspartate receptors remains unclear. alpha 2 delta-1, formerly known as a calcium channel subunit, interacts with N-methyl-d-aspartate receptors and is primarily expressed at presynaptic terminals. This study tested the hypothesis that alpha 2 delta-1-bound N-methyl-d-aspartate receptors contribute to presynaptic N-methyl-d-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance.