Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, No. 8, Gongtinan Road, Chaoyang District, 100020 Beijing, China.
Neurochem Res. 2011 Jan;36(1):170-6. doi: 10.1007/s11064-010-0288-y. Epub 2010 Oct 17.
Previous studies have demonstrated that the enhanced levels of phosphorylated α-amino-3-hydroxy-5-methyl-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.
先前的研究表明，脊髓背角中磷酸化的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体 GluR1 亚基丝氨酸-831（pGluR1-Ser-831）和丝氨酸-845（pGluR1-Ser-845）水平的升高与炎症性疼痛的中枢敏化有关。然而，AMPA 受体 GluR1 亚基的磷酸化调节是否参与术后疼痛的发展和维持仍不清楚。本研究旨在探讨在大鼠术后疼痛事件期间，通过 AMPA 受体 GluR1 亚基的磷酸化机制对其功能进行调节。我们的数据表明，在切口后 3 小时，同侧脊髓背角中 pGluR1-Ser-831 的表达显著增加，然后逐渐减少，在切口后 3 天恢复正常水平。同时，同侧脊髓背角中 pGluR1-Ser-845 和 GluR1 的表达保持不变。在切口后 3 小时，累积疼痛评分增加，随后逐渐减少，在切口后 4 天恢复到基线值，趋势与脊髓背角中 pGluR1-Ser-831 的表达变化几乎平行。鞘内注射钙依赖性蛋白激酶（PKC）抑制剂 Gö6983（10 μM）可显著逆转切口后 3 小时脊髓背角中 pGluR1-Ser-831 的过度表达，并降低累积疼痛评分。这些结果表明，在手术过程中，GluR1 亚基丝氨酸-831 和丝氨酸-845 位点的磷酸化可能受到不同的调节，并支持与磷酸化 AMPA 亚基 GluR1-Ser-831 而不是 pGluR1-Ser-845 相关的术后疼痛的神经生物学机制。我们的研究表明，针对 AMPA 受体 GluR1 亚基丝氨酸-831 位点磷酸化调节的治疗方法可能对治疗术后疼痛具有重要意义。
