Differential Roles of Phosphorylated AMPA Receptor GluR1 Subunits at Serine-831 and Serine-845 Sites in Spinal Cord Dorsal Horn in a Rat Model of Post-Operative Pain
Differential Roles of Phosphorylated AMPA Receptor GluR1 Subunits at Serine-831 and Serine-845 Sites in Spinal Cord Dorsal Horn in a Rat Model of Post-Operative Pain
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DOI：
10.1007/s11064-010-0288-y
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发表时间：
2010
影响因子：
4.4
通讯作者：
Yun Wang;Xiaobo Mu;Jing Wu;Anshi Wu;L. Fang;Junfa Li;Y. Yue
中科院分区：
文献类型：
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作者：
Yun Wang;Xiaobo Mu;Jing Wu;Anshi Wu;L. Fang;Junfa Li;Y. Yue
以往的研究表明，脊髓背角α-氨基-3-羟基-5-甲基-4-异恶唑(AMPA)受体丝氨酸-831(PGluR1Ser831)和丝氨酸-845(PGluR1Ser845)亚基的磷酸化水平升高参与了炎症性疼痛的中枢敏化。然而，AMPA受体GluR1亚单位的磷酸化调节是否与术后疼痛的发生和维持有关仍不清楚。本研究旨在探讨AMPA受体GluR1亚单位在大鼠术后疼痛过程中的功能调节机制。结果表明，pGluR1-Ser-831在同侧脊髓背角的表达在术后3h显著升高，然后逐渐下降，术后第3d恢复到正常水平。同时，pGluR1-Ser-845和GluR1在同侧脊髓背角的表达没有变化。术后3h累积疼痛评分升高，以后逐渐下降，术后4d恢复至基线值，其变化趋势与脊髓背角pGluR1-Ser-831的表达变化趋势基本一致。鞘内注射钙依赖蛋白激酶抑制剂Gö6983(10μM)可显著逆转切开后3h脊髓背角pGluR1Ser831的过度表达，并降低累积疼痛评分。这些结果表明，手术后GluR1丝氨酸-831和丝氨酸-845亚基的磷酸化可能受到不同的调节，支持了术后疼痛的神经生物学机制，涉及AMPA亚基GluR1-Ser-831的磷酸化，而不是pGluR1-Ser-845的磷酸化。我们的研究表明，靶向调节AMPA受体GluR1亚基丝氨酸-831位的磷酸化可能对术后疼痛的治疗具有重要意义。
Previous studies have demonstrated that the enhanced levels of phosphorylated α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor GluR1 subunits at Serine-831 (pGluR1-Ser-831) and Serine-845 (pGluR1-Ser-845) in the spinal cord dorsal horn are involved in central sensitization of inflammatory pain. However, whether the phosphorylatory regulation of AMPA receptor GluR1 subunits is implicated in the development and maintenance of post-operative pain remains unclear. The current study aims to examine the functional regulation of AMPA receptor GluR1 subunit through its phosphorylation mechanism during the period of post-operative painful events in rats. Our data indicated that the expression of pGluR1-Ser-831 in ipsilateral spinal cord dorsal horn increased significantly at 3 h after incision, then decreased gradually, and returned to the normal level 3 day post-incision. Meanwhile, the expression of pGluR1-Ser-845 and GluR1 in ipsilateral spinal cord dorsal horn remained unchanged. The cumulative pain scores increased at 3 h after incision, gradually decreased afterwards and returned to the baseline values at 4 day after incision and the trend was almost parallel to the expression changes of pGluR1-Ser-831 in spinal dorsal horn. Intrathecal injection of a calcium-dependent protein kinase (PKC) inhibitor, Gö6983 (10 μM), significantly reversed the incision-mediated over-expression of pGluR1-Ser-831 in spinal dorsal horn at 3 h after incision and decreased the cumulative pain scores as well. These results indicate that the phosphorylation of GluR1 subunits at Serine-831 and Serine-845 sites might be differentially regulated following surgical procedures and support a neurobiological mechanism of post-operative pain involved in phosphorylation of AMPA subunits GluR1-Ser-831, but not pGluR1-Ser-845. Our study suggests that the therapeutic targeting the phosphorylation regulation of AMPA receptor GluR1 subunit at Serine-831 site would be potentially significant for treating postoperative pain.