Altered glial glutamate transporter expression in descending circuitry and the emergence of pain chronicity

Molecular Pain
Wei GuoK Ren

Abstract

The glutamate type 1 transporter (GLT1) plays a major role in glutamate homeostasis in the brain. Although alterations of GLT1 activity have been linked to persistent pain, the significance of these changes is poorly understood. Focusing on the rostral ventromedial medulla, a key site in pain modulation, we examined the expression and function of GLT1 and related transcription factor kappa B-motif binding phosphoprotein (KBBP) in rats after adjuvant-induced hind paw inflammation. After inflammation, GLT1 and KBBP showed an early upregulation and gradual transition to downregulation that lasted throughout the eight-week observation period. Nitration of GLT1 was reduced at 30 min and increased at eight weeks after inflammation, suggesting an initial increase and later decrease in transporter activity. Mechanical hyperalgesia and paw edema exhibited an initial developing phase with peak hyperalgesia at 4 to 24 h, a subsequent attenuating phase, followed by a late persistent phase that lasted for months. The downregulation of GLT1 occurred at a time when hyperalgesia transitioned into the persistent phase. In the rostral ventromedial medulla, pharmacological block with dihydrokainic acid and RNAi of GLT1 and KBBP increased nocicept...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Psychology·Ana Carolina Pinheiro CamposRaquel Chacon Ruiz Martinez
Dec 23, 2020·International Journal of Molecular Sciences·Alison C Todd, Giles E Hardingham
Jul 19, 2020·Behavioural Brain Research·Guanyi LuJin Li

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Methods Mentioned

BETA
protein assay
electrophoresis
Infrared Imaging
immunoprecipitation
transfection

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