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Aquaporin 4 knockout increases complete freund's adjuvant-induced spinal central sensitization
1Jiangsu Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China.
Brain Research Bulletin
|January 14, 2020
Summary
Aquaporin 4 (AQP4) deficiency worsens pain sensitivity by impairing glutamate transporter 1 (GLT1) regulation in astrocytes. Targeting spinal AQP4 may treat inflammation-induced pain.
Area of Science:
- Neuroscience
- Pain Research
- Astrocyte Biology
Background:
- Astrocytes play a key role in pain regulation.
- The water channel protein aquaporin 4 (AQP4) is crucial for astrocyte function and implicated in neurological disorders.
- The specific role of AQP4 in pain pathophysiology is not well understood.
Purpose of the Study:
- To investigate the role of aquaporin 4 (AQP4) gene knockout in central sensitization.
- To determine the effect of AQP4 deficiency on pain behaviors and spinal cord mechanisms following Complete Freund's Adjuvant (CFA) injection.
Main Methods:
- Utilized AQP4 null mice and wild-type controls.
- Induced peripheral inflammation and central sensitization using intraplantar Complete Freund's Adjuvant (CFA) injection.
- Performed behavioral analyses for mechanical allodynia and thermal hyperalgesia.
- Assessed astrocyte activation, aquaporin 4 (AQP4), glutamate transporter 1 (GLT1) expression, neuronal activation marker Fos, and pro-inflammatory cytokines in the spinal cord dorsal horn.
Main Results:
- AQP4 null mice exhibited exacerbated mechanical allodynia and thermal hyperalgesia compared to wild-type controls post-CFA injection.
- CFA induced astrocyte activation with increased AQP4 and GLT1 expression in the spinal cord dorsal horn.
- AQP4 deficiency attenuated the compensatory upregulation of GLT1, leading to persistent neuronal activation (Fos expression) in superficial dorsal horn neurons.
- No significant effect of AQP4 deletion on CFA-evoked pro-inflammatory cytokine expression was observed.
Conclusions:
- Absence of AQP4 intensifies Complete Freund's Adjuvant (CFA)-induced spinal central sensitization.
- This intensification is linked to impaired compensatory upregulation of glutamate transporter 1 (GLT1), resulting in enhanced glutamatergic overexcitation.
- Targeting spinal cord AQP4 presents a potential therapeutic strategy for managing peripheral inflammation-evoked hyperalgesia.
