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

Abstract

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.