Inhibiting astrocytic activation: A novel analgesic mechanism of ketamine at the spinal level?

Xiaopeng Mei, Wei Wang, Wen Wang, Yunming Li, Hui Zhang, Shengxi Wu, Yunqing Li, Lixian Xu

Research output: Contribution to journalArticle

Abstract

Although ketamine is widely used as an analgesic agent and has an anti-allodynic effect on neuropathic pain, the underlying analgesic mechanisms are not fully explained by the modern 'neuronal-based' theories. As emerging studies have focused on the critical role of spinal astrocytes in the pathological pain states, we have hypothesized that there exist some 'astrocytes-related' mechanisms in the analgesic function of ketamine. In the present study, using the spinal nerve ligation (SNL) pain model, we investigated the anti-nociceptive effects of intraperitoneal or intrathecal ketamine on SNL-induced neuropathic pain response, meanwhile, we investigated the astrocytic activation after ketamine administration on SNL rats. Behavioral data showed that either intraperitoneal or intrathecal ketamine inhibited SNL-induced allodynia, however, immunohistochemistry showed that SNL induced astrocytic activation was suppressed by intrathecal but not intraperitoneal ketamine. Using quantitative Western blot analysis, our report showed that intrathecal ketamine down-regulated glial fibrillary acidic protein expression, suggesting inhibition of SNL-induced astrocytic activation, which wasn't influenced by intraperitoneal administration. We conclude that intraperitoneal ketamine could alleviate SNL-induced neuropathic pain via the classical 'neuronal-based' mechanisms, but in addition, 'astrocytes-related' mechanisms were also important underlying the anti-allodynic effect of intrathecal ketamine.

Original languageEnglish (US)
Pages (from-to)1691-1700
Number of pages10
JournalJournal of Neurochemistry
Volume109
Issue number6
DOIs
Publication statusPublished - Jun 1 2009
Externally publishedYes

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Keywords

  • Astrocytes
  • N-methyl-d-aspartate
  • Neuropathic pain
  • Spinal cord
  • Spinal nerve ligation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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