Spinal Microglial Expression and Mechanical Hypersensitivity in a Postoperative Pain Model: Comparison with a Neuropathic Pain Model

Spinal Microglial Expression and Mechanical Hypersensitivity in a Postoperative Pain Model: Comparison with a Neuropathic Pain Model
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DOI:
10.1097/aln.0b013e3181b05f42
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发表时间:
2009-09-01
期刊:
影响因子:
8.8
通讯作者:
Saito, Shigeru
Saito, Shigeru
中科院分区:
医学1区
文献类型:
--
作者:
Ito, Naomi;Obata, Hideaki;Saito, Shigeru

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背景:术后疼痛控制有助于提高生活质量。周围神经损伤后脊髓小胶质细胞的激活与机械超敏有关。然而,脊髓小胶质细胞在术后超敏反应中的作用尚不清楚。在这里,作者评估了抑制脊髓小胶质细胞是否降低了术后机械超敏反应,如果是,其效果是否与大鼠神经病理性疼痛模型不同。方法:雄性SD大鼠接受单侧足底后爪切开(术后疼痛模型)或L5脊神经切断(神经病理性疼痛模型),并使用von Frey细丝评估机械超敏反应的发展。小胶质细胞抑制剂米诺环素每天给药3天或7天。用OX42免疫组织化学方法检测脊髓小胶质细胞的激活情况。我们还测试了鞘内注射p38丝裂原活化蛋白激酶抑制剂SB203580的效果。结果:在术后疼痛模型中,米诺环素不能抑制机械过敏,但能抑制脊髓OX42表达的增加。相比之下,在神经病理性疼痛模型中,米诺环素以剂量相关的方式降低机械过敏,并抑制脊髓ox42的表达。SB203580可降低神经病理性疼痛模型中的过敏性,但在术后疼痛模型中无此作用。结论:脊髓OX42的表达在神经病理性疼痛的发生发展中起着比术后疼痛更重要的作用,脊髓OX42表达的增加与术后机械超敏反应无关。
Background: Postoperative pain control contributes to quality of life. Activation of spinal cord microglia after peripheral nerve injury contributes to mechanical hypersensitivity. The contribution of spinal cord microglia to hypersensitivity after surgery, however, is not well understood. Here, the authors evaluated whether inhibition of spinal microglia reduced postoperative mechanical hypersensitivity, and if so, whether the effect differed from that in a rat neuropathic pain model.Methods: Male Sprague-Dawley rats underwent either unilateral plantar hind paw incision (postoperative pain model) or L5 spinal nerve transection (neuropathic pain model), and the development of mechanical hypersensitivity was assessed using von Frey filaments. The microglial inhibitor minocycline was intraperitoneally administered daily for either 3 or 7 days. Spinal microglial activation was evaluated by OX42 immunohistochemistry. We also tested the effect of intrathecal administration of a p38 mitogen-activated protein kinase inhibitor, SB203580.Results: In the postoperative pain model, minocycline did not suppress mechanical hypersensitivity, but did inhibit an increase in spinal OX42 expression. In contrast, in the neuropathic pain model, minocycline reduced mechanical hypersensitivity in a dose-related manner and inhibited spinal ox42 expression. SB203580 attenuated hypersensitivity in the neuropathic pain model, but not in the postoperative pain model.Conclusions: The results of the present study suggest that spinal OX42 expression has a more important role in the development of neuropathic pain than in postoperative pain, and that an increase in spinal OX42 expression does not contribute to postoperative mechanical hypersensitivity.