Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation
Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation
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小胶质细胞和白介素 18 参与强直性坐骨神经刺激引起的脊髓伤害性反应的长期增强
DOI：
10.1007/s12264-012-1058-4
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发表时间：
2012-02-01
影响因子：
5.6
通讯作者：
Zhao, Zhi-Qi
中科院分区：
文献类型：
--
作者：
Chu, Yu-Xia;Zhang, Yu-Qiu;Zhao, Zhi-Qi
本研究旨在探讨脊髓小胶质细胞及其下游分子在强直刺激坐骨神经（TSS）诱导脊髓长时程增强（LTP）和机械性痛觉超敏中的作用。（0.5 ms，100 Hz，40 V，10列，持续时间2 s，间隔10 s）。使用von Frey毛发确定机械异常性疼痛。采用免疫组化和Western blot方法检测脊髓胶质细胞白细胞介素18（IL-18）及其受体（IL-18 R）的表达变化。在TSS前1 h鞘内注射小胶质细胞抑制剂米诺环素（200 μg/20 μL）可完全阻断脊髓LTP的诱导。此外，在TSS前1h腰椎穿刺鞘内注射米诺环素（200 μg/20 μL）后，连续7天（每天1次）给予米诺环素部分抑制双侧异常性疼痛。免疫组化结果表明，米诺环素抑制小胶质细胞和星形胶质细胞的顺序激活，和IL-18主要是共定位与小胶质细胞标记Iba-1在脊髓浅背角。Western blot结果显示，反复鞘内注射米诺环素可显著抑制TSS诱导的小胶质细胞IL-18和IL-18 Rs的表达增加。结论小胶质细胞IL-18信号通路参与TSS诱导的脊髓LTP和机械性异常性疼痛。
ObjectiveThe present study aimed to investigate the potential roles of spinal microglia and downstream molecules in the induction of spinal long-term potentiation (LTP) and mechanical allodynia by tetanic stimulation of the sciatic nerve (TSS).MethodsSpinal LTP was induced in adult male Sprague-Dawley rats by tetanic stimulation of the sciatic nerve (0.5 ms, 100 Hz, 40 V, 10 trains of 2-s duration at 10-s intervals). Mechanical allodynia was determined using von Frey hairs. Immunohistochemical staining and Western blot were used to detect changes in glial expression of interleukin-18 (IL-18) and IL-18 receptor (IL-18R).ResultsTSS induced LTP of C-fiber-evoked field potentials in the spinal cord. Intrathecal administration of the microglial inhibitor minocycline (200 μg/20 μL) 1 h before TSS completely blocked the induction of spinal LTP. Furthermore, after intrathecal injection of minocycline (200 μg/20 μL) by lumbar puncture 1 h before TSS, administration of minocycline for 7 consecutive days (once per day) partly inhibited bilateral allodynia. Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes, and IL-18 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn. Western blot revealed that repeated intrathecal injection of minocycline significantly inhibited the increased expression of IL-18 and IL-18Rs in microglia induced by TSS.ConclusionThe IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.