Tang Jun, Dong Jing, Yang Li, Gao Lingqi, Zheng Jijian
Department of Anesthesiology, Jinshan Hospital, Fudan University Shanghai, China.
Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.
Int J Clin Exp Med. 2015 Feb 15;8(2):2065-76. eCollection 2015.
Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.
伤害感受器中G蛋白偶联受体激酶2（GRK2）的短暂减少所诱导的持久神经可塑性变化会增强并延长炎症性痛觉过敏。在此，我们在I型复杂性区域疼痛综合征（CRPS-I）大鼠模型中研究了帕罗西汀（一种选择性5-羟色胺再摄取抑制剂和GRK2抑制剂）对颈上神经节（SCG）中GRK2表达的影响。缺血再灌注（I/R）损伤后，同侧对机械刺激的50% paw退缩阈值（PWTs）以及同侧SCG中GRK2蛋白和mRNA的表达水平均显著降低；同侧冷觉异常评分显著增加。除I/R损伤后第2天至第9天对侧GRK2 mRNA显著降低但仍高于同侧SCG外，对侧未发现显著差异。给予帕罗西汀后，第2天、第7天、第14天和第21天的同侧50% PWTs显著高于对照组；第1天后同侧SCG中GRK2蛋白和mRNA水平也显著上调；第7天后同侧冷觉异常评分显著降低。除帕罗西汀给药后第1天至第7天对侧GRK2 mRNA水平显著升高外，对侧50% PWTs、冷觉异常评分和GRK2蛋白水平未发现显著差异。因此，SCG神经元中GRK2表达的短暂降低可能参与了CRPS-I中异常性疼痛的发生和维持，而帕罗西汀可能通过上调SCG中的GRK2蛋白来减轻这种异常性疼痛。
