Papers of the Week

Presynaptic N-methyl-D-aspartate receptors contribute to opioid tolerance and hyperalgesia as well as neuropathic painThe α2δ-1 protein subunit enhances presynaptic N-methyl-D-aspartate receptor activity WHAT THIS ARTICLE TELLS US THAT IS NEW: Using mouse and rat models, it was demonstrated that α2δ-1 is essential for the increase in presynaptic N-methyl-D-aspartate receptor activity seen during chronic morphine exposureInhibiting α2δ-1 activity using gabapentin or genetically deleting the gene coding for α2δ-1 results in diminished opioid tolerance and hyperalgesia BACKGROUND:: Chronic use of μ-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. α2δ-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 α2δ-1-bound N-methyl-D-aspartate receptors contribute to presynaptic N-methyl-D-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance.