Abstract | BACKGROUND: We 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. METHODS: Immunofluorescence 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. RESULTS: The 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. CONCLUSIONS: The 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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Authors | Xiao-Peng Mei, Hui Zhang, Wei Wang, Yan-Yan Wei, Ming-Zhu Zhai, Wen Wang, Li-Xian Xu, Yun-Qing Li |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 8
Issue 1
Pg. 6
(Jan 24 2011)
ISSN: 1742-2094 [Electronic] England |
PMID | 21255465
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics
- Ketamine
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Analgesics
(pharmacology, therapeutic use)
- Animals
- Astrocytes
(drug effects, enzymology)
- Behavior, Animal
(drug effects)
- Enzyme Activation
- Hyperalgesia
- Injections, Spinal
- JNK Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Ketamine
(pharmacology, therapeutic use)
- Ligation
- Male
- Motor Activity
(drug effects)
- Neuralgia
(drug therapy)
- Pain Measurement
- Rats
- Rats, Sprague-Dawley
- Spinal Cord
(cytology)
- Spinal Nerves
(drug effects, physiopathology, surgery)
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