TY - JOUR
T1 - Inflammation-induced upregulation of AMPA receptor subunit expression in brain stem pain modulatory circuitry
AU - Guan, Yun
AU - Guo, Wei
AU - Zou, Shi Ping
AU - Dubner, Ronald
AU - Ren, Ke
N1 - Funding Information:
We thank E. Wade for her excellent technical support and Cynthia Renn for her comments on the draft. This work was supported by the National Institute on Drug Abuse Grant DA-10275.
PY - 2003/7
Y1 - 2003/7
N2 - Our previous study demonstrated an increase in α-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.
AB - Our previous study demonstrated an increase in α-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.
KW - Descending modulation
KW - GluR1
KW - Inflammatory hyperalgesia
KW - Rostral ventromedial medulla
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U2 - 10.1016/S0304-3959(03)00048-4
DO - 10.1016/S0304-3959(03)00048-4
M3 - Article
C2 - 12855351
AN - SCOPUS:0038161060
SN - 0304-3959
VL - 104
SP - 401
EP - 413
JO - Pain
JF - Pain
IS - 1-2
ER -