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Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain.

AbstractBACKGROUND:
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.
AuthorsXiao-Peng Mei, Hui Zhang, Wei Wang, Yan-Yan Wei, Ming-Zhu Zhai, Wen Wang, Li-Xian Xu, Yun-Qing Li
JournalJournal of neuroinflammation (J Neuroinflammation) Vol. 8 Issue 1 Pg. 6 (Jan 24 2011) ISSN: 1742-2094 [Electronic] England
PMID21255465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Analgesics
  • Ketamine
  • JNK Mitogen-Activated Protein Kinases
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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