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Cited by 283

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions

Open access
Chen, Jinjun, Li, Lingyong, Chen, Shao-Rui, Chen, Hong, Xie, Jing-Dun, Sirrieh, Rita E., MacLean, David M., Zhang, Yuhao, Zhou, Meng-Hua, Jayaraman, Vasanthi, Pan, Hui-Lin·2018·Cell Reports
DOI 10.1016/j.celrep.2018.02.021
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Abstract

channel subunit, is a binding site of gabapentinoids used to treat neuropathic pain and epilepsy. However, it is unclear how α2δ-1 contributes to neuropathic pain and gabapentinoid actions. Here, we show that Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. Conversely, Cacna2d1 knockdown or ablation normalizes synaptic NMDAR activity increased by nerve injury. α2δ-1 forms a heteromeric complex with NMDARs in rodent and human spinal cords. The α2δ-1-NMDAR interaction predominantly occurs through the C terminus of α2δ-1 and promotes surface trafficking and synaptic targeting of NMDARs. Gabapentin or an α2δ-1 C terminus-interfering peptide normalizes NMDAR synaptic targeting and activity increased by nerve injury. Thus, α2δ-1 is an NMDAR-interacting protein that increases NMDAR synaptic delivery in neuropathic pain. Gabapentinoids reduce neuropathic pain by inhibiting forward trafficking of α2δ-1-NMDAR complexes.

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Metadata

Authors
Chen, J., Li, L., Chen, S.-R., Chen, H., Xie, J.-D., Sirrieh, R. E., MacLean, D. M., Zhang, Y., Zhou, M.-H., Jayaraman, V., & Pan, H.-L.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2018-02
Volume
22
Issue
9
Pages
2307-2321
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2018.02.021
OpenAlex
W2793983403
Cited by
283
References
52
FWCI
15.44
Type
journal article
Language
en
Open access
gold

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