Ito Naomi, Obata Hideaki, Saito Shigeru
Department of Anesthesiology, Gunma University Graduate School of Medicine, Showa, Maebashi, Gunma, Japan.
Anesthesiology. 2009 Sep;111(3):640-8. doi: 10.1097/ALN.0b013e3181b05f42.
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.
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.
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.
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.
术后疼痛控制有助于提高生活质量。外周神经损伤后脊髓小胶质细胞的激活会导致机械性超敏反应。然而，脊髓小胶质细胞在术后超敏反应中的作用尚未得到充分了解。在此，作者评估了抑制脊髓小胶质细胞是否能降低术后机械性超敏反应，如果是，其效果是否与大鼠神经性疼痛模型不同。
雄性Sprague-Dawley大鼠接受单侧足底后爪切开术（术后疼痛模型）或L5脊髓神经横断术（神经性疼痛模型），并使用von Frey细丝评估机械性超敏反应的发展。小胶质细胞抑制剂米诺环素每天腹腔注射3天或7天。通过OX42免疫组织化学评估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。
在术后疼痛模型中，米诺环素并未抑制机械性超敏反应，但确实抑制了脊髓OX42表达的增加。相比之下，在神经性疼痛模型中，米诺环素以剂量相关的方式降低了机械性超敏反应，并抑制了脊髓OX42表达。SB203580减轻了神经性疼痛模型中的超敏反应，但在术后疼痛模型中没有效果。
本研究结果表明，脊髓OX42表达在神经性疼痛的发展中比在术后疼痛中起更重要的作用，并且脊髓OX42表达的增加对术后机械性超敏反应没有影响。
