Increased glial glutamate transporter EAAT2 expression reduces visceral nociceptive response in mice

Yuan Lin, Guilian Tian, Kenny Roman, Chalonda Handy, Joseph B. Travers, Chien Liang Glenn Lin, Robert L. Stephens

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Visceral hypersensitivity is the leading complaint of functional bowel disorders. Central sensitization mediated by glutamate receptor activation is implicated in pathophysiology of visceral pain. The glial glutamate transporter EAAT2 is the principal mediator of glutamate clearance to terminate glutamate-mediated responses. Transgenic mice overexpressing human EAAT2 (EAAT2 mice), which exhibited a twofold enhanced glutamate uptake, showed 39% less writhing response to intraperitoneal acetic acid than nontransgenic littermates. Moreover, EAAT2 transgenic mice showed a 53-64% reduction in visceromotor response (VMR) to colorectal distension (CRD) in assessments of the response to graded increase in pressures. Corroborating the involvement of enhanced glutamate uptake, wild-type mice treated for 1 wk with ceftriaxone, an EAAT2 expression activator, showed a 49-70% reduction in VMR to CRD. Moreover, systemic pretreatment with the selective EAAT2 transporter blocker dihydrokainate reversed the ceftriaxone-blunted nociceptive response to CRD. However, the enhanced VMR to CRD produced by intracolonic ethanol was not significantly attenuated by 1-wk ceftriaxone pretreatment. The data suggest that enhanced glutamate uptake provides protective effects against colonic distension-induced nociception and represents an exciting new mechanistic approach leading to better therapeutic options to visceral pain disorders.

Original languageEnglish (US)
Pages (from-to)G129-G134
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume296
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Colon
  • Excitatory amino acids
  • Gastrointestinal
  • Pain

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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