Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain.
Spinal AMPA Receptor GluA1 Ser831 Phosphorylation Controls Chronic Alcohol Consumption-Produced Prolongation of Postsurgical Pain.
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脊髓 AMPA 受体 GluA1 Ser831 磷酸化控制慢性饮酒导致的术后疼痛延长
DOI：
10.1007/s12035-017-0639-7
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发表时间：
2018-05
影响因子：
5.1
通讯作者：
Tao F
中科院分区：
文献类型：
--
作者：
Liu S;Zhao Z;Guo Y;Shu H;Li C;Tang Y;Xing Y;Tao F
先前的研究表明，过量饮酒与慢性疼痛的发展有关；然而，这种联系背后的分子机制却知之甚少。在这项研究中，我们调查了长期饮酒对足底切开引起的术后疼痛的影响。我们观察到，4周的饮酒显著延长了足底切开引起的机械性疼痛，而不是热痛感。慢性酒精摄入增加了足底切口处产生的α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸(AMPA)受体GluA1在脊髓的Ser831位点的磷酸化。GluA1 S831a突变小鼠的GluA1磷酸化位点的靶向突变显著抑制了慢性饮酒引起的切口痛延长。此外，慢性饮酒和足底切开显著增加脊髓背角神经元AMPA受体介导的微小兴奋性突触后电流，而这种作用在GluA1 S831a突变小鼠中显著减弱。我们的结果提示，长期饮酒可能通过增强AMPA受体GluA1 Ser831的磷酸化而促进术后持续性疼痛的发生。我们确定长期饮酒是手术后疼痛慢性化的危险因素。
Previous studies have shown that excessive alcohol drinking is associated with chronic pain development; however, the molecular mechanism underlying this association is poorly understood. In this study, we investigated the effect of chronic alcohol consumption on plantar incision-induced postsurgical pain. We observed that 4-week ethanol drinking significantly prolonged plantar incision-induced mechanical pain, but not thermal pain. The chronic alcohol consumption enhanced plantar incision-produced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 phosphorylation at the Ser831 site in the spinal cord. The targeted mutation of the GluA1 phosphorylation site in GluA1 S831A mutant mice significantly inhibited the incisional pain prolongation produced by chronic alcohol consumption. Moreover, chronic alcohol consumption combined with plantar incision markedly increased AMPA receptor-mediated miniature excitatory postsynaptic currents in the spinal dorsal horn neurons, and this effect was diminished significantly in the GluA1 S831A mutant mice. Our results suggest that chronic alcohol consumption may promote the development of persistent postsurgical pain by enhancing AMPA receptor GluA1 Ser831 phosphorylation. We identified chronic alcohol consumption as a risk factor for pain chronification after surgery.
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
25
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影响因子：
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