Background & Aims
The N-Methyl-D-aspartate receptor (NMDAR) GluN2B subtype is gaining attention because blocking of its activity is reported to reduce neuropathic pain with minimal side effects. However, the effectiveness of GluN2B antagonists on neuropathic pain following peripheral nerve injury and the signal transduction pathways associated with GluN2B activation remain known.
Methods
After spinal nerve ligation (SNL), we investigated the temporal changes in GluN2B, as well as its phosphorylation sites at Ser1303 and at Tyr1472, calcium/calmodulin-dependent protein kinase II ? (CaMKII?) in the L5 dorsal spinal cord. To examine the interaction between GluN2B Ser1303 and CaMKII, we used co-immunoprecipitation. Mechanical paw withdrawal threshold (PWT) was measured before and after intrathecal administration of GluN2B antagonist in SNL.
Results
Protein expression of GluN2B increased from 6 hours to 4 days and GluN2B Ser1303 phosphorylation increased up to 2 weeks. The interaction between GluN2B Ser1303 and CaMKII? was robustly enhanced from 6 hours to 4 days after the injury. Furthermore, intrathecal administration of the GluN2B antagonist Ro25-6981 in the early phase reduced mechanical PWT. Additionally, pre-emptive intrathecal infusion of GluN2B antagonist did not induce mechanical paw hypersensitivity after peripheral nerve injury.
Conclusions
These results demonstrate that GluN2B signaling can initiate mechanical paw hypersensitivity after peripheral nerve injury.
References
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Huang L-E, Guo S-H, Thitiseranee L, Yang Y, Zhou Y-F, Yao Y-X. N-methyl D-aspartate receptor subtype 2B antagonist, Ro 25-6981, attenuates neuropathic pain by inhibiting postsynaptic density 95 expression. Scientific Reports 2018;8: 7848
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