| First Author | Nozaki C | Year | 2011 |
| Journal | Nat Neurosci | Volume | 14 |
| Issue | 8 | Pages | 1017-22 |
| PubMed ID | 21725314 | Mgi Jnum | J:175900 |
| Mgi Id | MGI:5287913 | Doi | 10.1038/nn.2844 |
| Citation | Nozaki C, et al. (2011) Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nat Neurosci 14(8):1017-22 |
| abstractText | Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+-NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation. |
