Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain.
Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain.
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脊髓星形细胞 c-Jun N 末端激酶 (JNK) 激活的抑制与氯胺酮在神经性疼痛中的镇痛作用相关
DOI：
10.1186/1742-2094-8-6
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发表时间：
2011-01-24
影响因子：
9.3
通讯作者：
Li YQ
中科院分区：
文献类型：
--
作者：
Mei XP;Zhang H;Wang W;Wei YY;Zhai MZ;Wang W;Xu LX;Li YQ
背景我们之前曾报道，星形胶质细胞活化的抑制有助于鞘内注射氯胺酮对脊神经结扎（SNL）引起的神经性疼痛的镇痛作用。然而，其根本机制仍不清楚。 c-Jun N 末端激酶 (JNK) 是丝裂原激活蛋白激酶 (MAPK) 家族的成员，据报道对于 SNL 后脊髓星形细胞激活和神经性疼痛发展至关重要。氯胺酮可以降低脂多糖（LPS）诱导的磷酸化 JNK（pJNK）表达，从而发挥其抗炎作用。我们推测氯胺酮对SNL诱导的脊髓星形胶质细胞活化的抑制作用可能与抑制星形胶质细胞JNK活化有关。方法采用免疫荧光组织化学染色检测SNL诱导的脊髓pJNK表达和定位。行为测试证实了氯胺酮对 SNL 引起的机械异常性疼痛的影响。免疫荧光组织化学和蛋白质印迹用于量化氯胺酮给药后 SNL 诱导的脊髓 pJNK 表达。结果本研究表明，SNL 诱导星形胶质细胞同侧 pJNK 上调，但不诱导脊髓背角内的小胶质细胞或神经元。鞘内注射氯胺酮可缓解 SNL 引起的机械异常性疼痛，且不会干扰运动功能。此外，鞘内注射氯胺酮以剂量依赖性方式减弱SNL诱导的脊髓星形胶质细胞JNK活化，但不减弱JNK蛋白表达。结论目前的结果表明，抑制JNK活化可能与氯胺酮对SNL诱导的脊髓星形胶质细胞活化的抑制作用有关。因此，抑制脊髓 JNK 激活可能与氯胺酮对 SNL 诱导的神经病理性疼痛的镇痛作用有关。
BackgroundWe have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation.MethodsImmunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration.ResultsThe present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression.ConclusionsThe present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.
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影响因子：
6.2
作者：
Bettoni, Isabella;Comelli, Francesca;Costa, Barbara
通讯作者：
Costa, Barbara
影响因子：
7.4
作者：
Ma, WY;Quirion, R
通讯作者：
Quirion, R
影响因子：
3.6
作者：
Lee, Kyung-Min;Jeon, Sang-Min;Cho, Hee-Jung
通讯作者：
Cho, Hee-Jung
影响因子：
7.4
作者：
Piao, ZG;Cho, IH;Oh, SB
通讯作者：
Oh, SB
影响因子：
2.5
作者：
Gao, Yong-Jing;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong