Inflammation-induced upregulation of AMPA receptor subunit expression in brain stem pain modulatory circuitry.

Abstract

Our previous study demonstrated an increase in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor sensitivity in the rostral ventromedial medulla (RVM) associated with enhanced net descending inhibition after inflammatory hyperalgesia. The present study further studied the time-dependent changes in AMPA-produced inhibition after inflammation and the underlying molecular mechanisms. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA, 0.2ml). There was a significant increase in AMPA-produced inhibition at 5h that was further enhanced at 24h (P<0.05), as compared to that at 3h post-inflammation. The AMPA-produced inhibition returned to the control level at 14 days post-inflammation. We analyzed mRNA and protein levels of the GluR1 and GluR2 AMPA receptor subunits in the RVM at 2h to 14 days post-inflammation. AMPA receptor subunits exist in the two 'flip' and 'flop' isoforms that differentially affect the desensitization properties of the receptor. Reverse transcription-polymerase chain reaction analysis indicated that there was a significant upregulation of mRNAs encoding the GluR1-flip (5-24h), GluR2-flip (24h) and GluR2-flop (24h) isoforms in the RVM after inflammation, whereas the levels of GluR1-flop mRNAs showed no significant change. Western blots demonstrated that the GluR1 protein levels were significantly upregulated at 24h-3 days (P<0.05) post-inflammation, compared to that of naive animals. GluR2 protein levels remained unchanged. Immunohistochemistry further demonstrated an increase in GluR1-like immunoreactivity localized to the RVM at 24h post-inflammation. These findings suggest that AMPA receptors in the RVM undergo selective transcriptional and translational modulation following inflammation and may contribute to activity-dependent plasticity in descending pain modulatory systems after prolonged noxious input.

• Authors: Yun Guan, Wei Guo, Shi-Ping Zou, Ronald Dubner, Ke Ren
• Journal: Pain (Pain) Vol. 104 Issue 1-2 Pg. 401-13 (Jul 2003) ISSN: 0304-3959 [Print] United States
• PMID: 12855351 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Protein Subunits
• Receptors, AMPA
• glutamate receptor ionotropic, AMPA 2
• glutamate receptor ionotropic, AMPA 1

Topics

• Animals
• Brain Stem (chemistry, metabolism)
• Gene Expression Regulation (genetics)
• Inflammation (metabolism, physiopathology)
• Male
• Neural Pathways (metabolism)
• Pain (metabolism)
• Protein Subunits (biosynthesis, genetics)
• Rats
• Rats, Sprague-Dawley
• Receptors, AMPA (analysis, biosynthesis, genetics)
• Up-Regulation (physiology)