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Papers of the Week

Papers: 7 Mar 2020 - 13 Mar 2020

Animal Studies, Pharmacology/Drug Development

2020 Mar 07


Disabling phosphorylation at the homer ligand of the metabotropic glutamate receptor 5 alleviates complete Freund’s adjuvant-induced inflammatory pain.


Luo L, Huang M, Zhang Y, Wang W, Ma X, Shi H, Worley PF, Kim D K, Fedorovich SV, Jiang W, Xu T
Neuropharmacology. 2020 Mar 07:108046.
PMID: 32156549.


Metabotropic glutamate receptor 5 (mGluR5) has been reported to contribute to inflammatory pain. The intracellular C-terminal domain has a Homer-binding motif that can form an mGluR5/Homer complex. Phosphorylation of mGluR5 at the Homer binding domain enhances the mGluR5/Homer interaction and modulates intracellular signal transduction. However, the characteristics of this interaction have not been fully elucidated in inflammatory pain. We aimed to evaluate the effects of CFA-induced phosphorylation of mGluR5 at the Homer binding domain on the mGluR5/Homer interaction. Von-frey filaments and thermal latency were used to monitor the development of inflammatory pain. Spinal mGluR5 phosphorylation at Ser and mGluR5/Homer crosslinking were detected. Mutant mGluR5 that could not be phosphorylated at Thr or Ser was evaluated in inflammatory pain. CFA-induced inflammatory pain resulted in obvious phosphorylation at Ser of mGluR5. Moreover, increased phosphorylation at the Homer-binding motif enhanced crosslinking between mGluR5 and Homer. Mutations at Thr and Ser of mGluR5 blocked the development of CFA-induced inflammatory pain. Overall, our findings showed that disruption of the phosphorylation of mGluR5 Thr and Ser alleviated CFA-induced inflammatory pain.