Aquaporin 4 knockout increases complete freund's adjuvant-induced spinal central sensitization

Cong Wang, Qi Wu, Ze Wang, Liang Hu, Charles Marshall, Ming Xiao

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Growing evidence suggests a critical role of astrocytes for pain regulation. The water channel protein aquaporin 4 (AQP4), a functional regulator of astrocytes, is involved in various neurological disorders. However, the pathophysiological roles of AQP4 in pain conditions remain unclear. In the present study, we investigated the effect of AQP4 gene knockout in central sensitization induced by complete Freund's adjuvant (CFA). The behavioral analysis revealed that mechanical allodynia and thermal hyperalgesia were more severe in AQP4 null mice than those of wild-type controls over the course of 11 days following CFA intraplantar injection. CFA caused activation of astrocytes with upregulated expression levels of AQP4 and glutamate transporter 1 (GLT1) in the dorsal horn of the spinal cord. AQP4 deficiency reduced GLT1 up-regulation, causing persistent expression of the neuronal activation marker Fos within superficial dorsal horn neurons, including glutamatergic neurons. However, AQP4 deletion did not affect CFA-evoked proinflammatory cytokine expression in the spinal cord. Together, these results have shown that AQP4 absence intensifies CFA-induced spinal central sensitization, which is associated with reduced compensatory up-regulation of GLT1, subsequently increasing glutamatergic overexcitation. Therefore, targeting spinal cord AQP4 may serve as a potential strategy for treatment of peripheral inflammation-evoked hyperalgesia.

Original languageEnglish
Pages (from-to)58-66
Number of pages9
JournalBrain Research Bulletin
StatePublished - Mar 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.


  • Aquaporin 4
  • Astrocytes
  • Complete freund's adjuvant
  • Glutamate transporter 1
  • Pain

ASJC Scopus subject areas

  • General Neuroscience


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