Intrathecal interleukin-β administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord
Intrathecal interleukin-β administration induces thermal hyperalgesia by activating inducible nitric oxide synthase expression in the rat spinal cord
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DOI：
10.1016/j.brainres.2004.04.068
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发表时间：
2004-07-23
期刊：
影响因子：
2.9
通讯作者：
Wong, CS
中科院分区：
文献类型：
--
作者：
Sung, CS;Wen, ZH;Wong, CS
在完整的大鼠脊髓中检测促炎细胞因子白细胞介素-1 β（IL-1 β）对伤害性信号转导中诱导型一氧化氮合酶-一氧化氮（iNOS-NO）级联反应的影响。所有大鼠均植入鞘内（i.t.）导管;有些人还植入了i.t.微透析探针使用对辐射热的缩爪潜伏期来评估热痛觉过敏。免疫印迹法和NOS活性测定法检测脊髓后角iNOS蛋白表达。还测量了CSF透析液中的NO产生。IL-1 β i.t. (100 ng）在i.t.后4至24小时产生热痛觉过敏注射i.t.后4 h诱导iNOS蛋白表达。IL-1 β注射后6 h达高峰，24 h消失。iNOS活性与iNOS蛋白表达呈时间依赖性变化。NO释放在4 ~ 12 h增加1.1 ~ 1.9倍，也在6 h达高峰。IL-1 β给药。用iNOS抑制剂1400 W（10 μ g，i.t.）i.t.前1 h IL-1 β注射可阻断IL-1 β的所有反应。140 OW和人工CSF（aCSF）对热伤害性阈值和NO产生均无影响。这些结果表明，i.t. IL-1 β通过激活大鼠脊髓中iNOS-NO级联反应诱导热痛觉过敏。根据目前的研究结果，我们建议，i.t.给予iNOS抑制剂可能具有治疗炎症性和神经性疼痛综合征的潜力。(C)2004 Elsevier B. V.保留所有权利。
The effect of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) on the inducible nitric oxide synthase-nitric oxide (iNOS-NO) cascade in nociceptive signal transduction was examined in the intact rat spinal cord. All rats were implanted with an intrathecal (i.t.) catheter; some were also implanted with an i.t. microdialysis probe. The paw withdrawal latency to radiant heat was used to assess thermal hyperalgesia. The iNOS protein expression in the spinal cord dorsal horn was examined by western blot analysis and NOS activity assay. NO production in the CSF dialysate was also measured. IL-1beta i.t. (100 ng) produced thermal hyperalgesia from 4 to 24 h after i.t. injection. The iNOS protein expression was induced at 4 h after i.t. IL-1beta injection, peaked at the 6th hour, and disappeared at 24 h. The iNOS activity showed a similar time-dependent change as the iNOS protein expression. NO release increased by 1.1- to 1.9-fold between 4 and 12 h, also with a peak at the 6th hour, after i.t. IL-1beta administration. Pretreatment with the iNOS inhibitor 140OW (10 mug, i.t.) 1 h before i.t. IL-1beta injection prevented all the responses of IL-1beta. Neither 140OW nor artificial CSF (aCSF) affected the thermal nociceptive threshold and NO production. These results demonstrate that i.t. administration of IL-1beta induced thermal hyperalgesia by activating the iNOS-NO cascade in the rat spinal cord. On the basis of the present findings, we suggest that i.t. administration of iNOS inhibitors may have potential in the treatment of inflammatory and neuropathic pain syndromes. (C) 2004 Elsevier B.V. All rights reserved.