RGS4 maintains chronic pain symptoms in rodent models

Kleopatra Avrampou, Kerri D. Pryce, Aarthi Ramakrishnan, Farhana Sakloth, Sevasti Gaspari, Randal A. Serafini, Vasiliki Mitsi, Claire Polizu, Cole Swartz, Barbara Ligas, Abigail Richards, Li Shen, Fiona B. Carr, Venetia Zachariou

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Regulator of G-protein signaling 4 (RGS4) is a potent modulator of G-protein-coupled receptor signal transduction that is expressed throughout the pain matrix. Here, we use genetic mouse models to demonstrate a role of RGS4 in the maintenance of chronic pain states in male and female mice. Using paradigms of peripheral inflammation and nerve injury, we show that the prevention of RGS4 action leads to recovery from mechanical and cold allodynia and increases the motivation for wheel running. Similarly, RGS4KO eliminates the duration of nocifensive behavior in the second phase of the formalin assay. Using the Complete Freud's Adjuvant (CFA) model of hindpaw inflammation we also demonstrate that downregulation of RGS4 in the adult ventral posterolateral thalamic nuclei promotes recovery from mechanical and cold allodynia. RNA sequencing analysis of thalamus (THL) from RGS4WT and RGS4KO mice points to many signal transduction modulators and transcription factors that are uniquely regulated in CFA-treated RGS4WT cohorts. Ingenuity pathway analysis suggests that several components of glutamatergic signaling are differentially affected by CFA treatment between RGS4WT and RGS4KO groups. Notably, Western blot analysis shows increased expression of metabotropic glutamate receptor 2 in THL synaptosomes of RGS4KO mice at time points at which they recover from mechanical allodynia. Overall, our study provides information on a novel intracellular pathway that contributes to the maintenance of chronic pain states and points to RGS4 as a potential therapeutic target.

Original languageEnglish
Pages (from-to)8291-8304
Number of pages14
JournalJournal of Neuroscience
Issue number42
StatePublished - Oct 2019


  • Genetic mouse models
  • Inflammatory pain
  • Neuropathic pain
  • RGS
  • RNA sequencing
  • Viral gene transfer


Dive into the research topics of 'RGS4 maintains chronic pain symptoms in rodent models'. Together they form a unique fingerprint.

Cite this