Spinal CCL1/CCR8 regulates phosphorylation of GluA1-containing AMPA receptor in postoperative pain after tibial fracture and orthopedic surgery in mice
Spinal CCL1/CCR8 regulates phosphorylation of GluA1-containing AMPA receptor in postoperative pain after tibial fracture and orthopedic surgery in mice
复制标题
脊髓 CCL1/CCR8 在小鼠胫骨骨折和骨科手术术后疼痛中调节含 GluA1 AMPA 受体的磷酸化。
DOI：
10.1016/j.neures.2019.05.003
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发表时间：
2020-05-01
影响因子：
2.9
通讯作者：
Yu, Yonghao
中科院分区：
文献类型：
--
作者：
Wang, Chunyan;Xu, Rubin;Yu, Yonghao
慢性术后疼痛可能是阻碍骨折和骨科手术后恢复功能的关键因素。然而，潜在的机制在很大程度上仍不清楚。兴奋性突触的AMPA受体因其在病理性疼痛中的关键作用而被认为。趋化因子CCL1相关的神经炎症在兴奋性突触传递和伤害性信息传递中发挥作用。本研究探讨了脊柱CCL1是否通过AMPA受体与骨折相关的术后疼痛有关。我们在此发现，骨科手术的胫骨骨折引发并维持了慢性术后疼痛，同时脊髓CCL1/CCR8表达上调和含有GluA1的AMPA受体磷酸化。中枢抑制CCL1/CCR8可损害机械痛觉和冷痛，并使脊髓背角内含GluAl的AMPA受体磷酸化。鞘内注射含GluAl的AMPA受体拮抗剂NASPM可减轻骨折相关的术后疼痛。此外，外源性CCL1传递促进了幼小鼠的急性疼痛行为和含有GluAl的AMPA受体的脊髓磷酸化，这一作用可通过联合应用NASPM而逆转。我们目前的结果表明，脊髓CCL1/CCR8介导的含GluAl的AMPA受体激活在小鼠骨折相关术后疼痛的发病机制中起着至关重要的作用。(C)《2019年》，爱思唯尔出版。
Chronic postoperative pain might be a pivotal component hindering recovery and regains the function after bone fracture and orthopedic surgery. However, the underlying mechanisms remain largely unclear. AMPA receptor of excitatory synapses is considered due to its critical role in pathologic pain. Chemokine CCL1 related neuroinflammation plays a role in excitatory synaptic transmission and nociceptive transduction. This study examined whether spinal CCL1 is associated with fracture-associated postoperative pain via AMPA receptor.We herein discovered that the tibial fracture with orthopedic surgery initiated and maintained chronic postoperative pain along with spinal up-regulation of CCL1/CCR8 expression and phosphorylation of GluAl-containing AMPA receptor. Central CCL1/CCR8 inhibition impaired mechanical and cold allodynia, and phosphorylated GluAl-containing AMPA receptor in the spinal dorsal horn. Intrathecal injection of GluAl-containing AMPA receptor antagonist NASPM alleviated fracture-related postoperative pain. Also, exogenous CCL1 delivery facilitated acute pain behaviors and spinal phosphorylation of GluAl-containing AMPA receptor in na ve mice, reversing by co-application of NASPM. Our current results indicated that spinal CCL1/CCR8-mediated GluAl-containing AMPA receptor activation is vital in the pathogenesis of fracture associated postoperative pain in mice. (C) 2019 Published by Elsevier B.V.