Li Li, Wu Yongfang, Bai Zhifeng, Hu Yuyan, Li Wenbin
a Central Laboratory, Department of Science and Technology , The Second Hospital of Hebei Medical University , Shijiazhuang , China.
b Department of Pathophysiology , Hebei Medical University , Shijiazhuang , China.
Neurol Res. 2017 Mar;39(3):271-280. doi: 10.1080/01616412.2017.1281198. Epub 2017 Jan 25.
Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats.
The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot.
After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom.
It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.
脊髓背角的小胶质细胞可被伤害性刺激激活，激活的小胶质细胞释放多种细胞因子，增强伤害性信号传递。然而，伤害性刺激期间脊髓小胶质细胞激活的潜在机制尚未完全明确。为了明确N-甲基-D-天冬氨酸（NMDA）受体在伤害性刺激期间脊髓小胶质细胞激活中的作用，本研究旨在探讨阻断NMDA受体对大鼠急性外周炎性疼痛诱导的脊髓小胶质细胞激活的影响。
通过向大鼠后爪足底皮下注射蜂毒诱导急性炎性疼痛。对自发疼痛行为、热退缩潜伏期和机械退缩阈值进行评分。采用免疫组织化学和蛋白质印迹法检测特异性小胶质细胞标志物CD11b/c的表达。
蜂毒处理后，发现大鼠出现单相伤害性反应，表现为持续抬起和舔舐注射的后爪、热退缩潜伏期缩短和机械退缩阈值降低；免疫组织化学显示小胶质细胞胞体增大，细胞突起增厚、延长且分支少、棘突小，免疫染色增强；蛋白质印迹显示在痛觉过敏期CD11b/c表达水平上调。鞘内预先注射NMDA受体选择性拮抗剂MK-801可减轻疼痛行为，并抑制蜂毒诱导的CD11b/c上调。
可以得出结论，NMDA受体参与介导大鼠蜂毒诱导的外周炎性疼痛和痛觉过敏中脊髓小胶质细胞的激活。
