Down-regulation of stargazin inhibits the enhanced surface delivery of α-Amino-3-hydroxy-5-methyl-4- Isoxazole propionate receptor GluR1 subunit in rat dorsal horn and ameliorates postoperative pain

Ruijuan Guo, Yujie Zhao, Meijuan Zhang, Rong Shi, Yang Liu, Jie Xu, Anshi Wu, Yun Yue, Jing Wu, Yun Guan, Yun Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5- Methyl-4-isoxazole propionate (AMPA) receptors. However, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development. Methods: Western blot analysis was used to examine changes in the surface delivery of AMPA receptor subunits, GluR1 and GluR2, in rat dorsal horn. The interaction between stargazin and GluR1 and GluR2 was examined by coimmunoprecipitation. Expression of stargazin was suppressed by intrathecal administration of small interfering RNA311. Results: Membrane-bound GluR1, but not GluR2, in ipsilateral dorsal horn was increased at 3 h (1.49 ± 0.15-fold of β-tubulin, mean ± SEM) and 1 day (1.03 ± 0.25) after incision, as compared with that in control rats (naive, 0.63 ± 0.23, P < 0.05, n = 6 per group). The amount of GluR1 coimmunoprecipitated with stargazin was greater at 3 h after incision (1.48 ± 0.31-fold of input) than that in control animals (0.45 ± 0.24, P < 0.05, n = 6 per group). Importantly, the increase in membrane GluR1 at 3 h after incision was normalized to near control level (0.72 ± 0.20-fold of β-tubulin) by pretreatment with intrathecal stargazin small interfering RNA311 (0.87 ± 0.09), but not scrambled small interfering RNA (1.48 ± 0.24) or vehicle (1.25 ± 0.13, P < 0.05, n = 6 per group). Stargazin small interfering RNA311 pretreatment prevented the increase in stargazin-GluR1 interaction and decreased postoperative pain after incision. Conclusions: This study suggests a critical role of stargazin-mediated surface delivery of GluR1 subunit in the development of postoperative pain. A better therapeutic strategy for postoperative pain may involve selectively down-regulating spinal stargazin to inhibit synaptic targeting of GluR1 subunit.

Original languageEnglish (US)
Pages (from-to)609-619
Number of pages11
JournalAnesthesiology
Volume121
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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