RGS4 Maintains Chronic Pain Symptoms in Rodent Models.
RGS
RNA sequencing
genetic mouse models
inflammatory pain
neuropathic pain
viral gene transfer
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
16 10 2019
16 10 2019
Historique:
received:
16
12
2018
revised:
02
05
2019
accepted:
27
06
2019
pubmed:
17
7
2019
medline:
4
7
2020
entrez:
17
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31308097
pii: JNEUROSCI.3154-18.2019
doi: 10.1523/JNEUROSCI.3154-18.2019
pmc: PMC6794935
doi:
Substances chimiques
RGS Proteins
0
RGS4 protein
175335-35-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8291-8304Subventions
Organisme : NIDA NIH HHS
ID : P01 DA047233
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA007135
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS098264
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS111351
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS086444
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS093537
Pays : United States
Informations de copyright
Copyright © 2019 the authors.
Références
Neuron. 2012 Jan 26;73(2):347-59
pubmed: 22284188
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Sci Rep. 2017 Sep 4;7(1):10406
pubmed: 28871199
J Neurosci. 2003 Sep 3;23(22):8098-108
pubmed: 12954872
Brain Res. 2004 Jul 16;1014(1-2):197-208
pubmed: 15213004
PLoS One. 2012;7(8):e40930
pubmed: 22879882
Mol Interv. 2009 Oct;9(5):234-51
pubmed: 19828831
Neuron. 2019 Jun 5;102(5):944-959.e3
pubmed: 31030955
J Clin Invest. 2010 Nov;120(11):3779-87
pubmed: 21041960
Anesth Analg. 2015 Mar;120(3):671-7
pubmed: 25695583
Pharmacol Rev. 2015;67(1):36-73
pubmed: 25361914
J Pharmacol Exp Ther. 2007 Nov;323(2):650-7
pubmed: 17693584
J Pain. 2009 Sep;10(9):895-926
pubmed: 19712899
Pain. 2018 May;159(5):849-863
pubmed: 29319606
Br J Pharmacol. 2015 Nov;172(22):5333-46
pubmed: 26478461
J Neurosci. 1991 Mar;11(3):852-68
pubmed: 1705972
J Pain. 2003 Oct;4(8):465-70
pubmed: 14622667
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18820-4
pubmed: 19843694
Biol Psychiatry. 2006 Sep 15;60(6):534-7
pubmed: 16860780
Pain. 2012 Apr;153(4):876-84
pubmed: 22341563
J Neurol Neurosurg Psychiatry. 2015 Sep;86(9):973-85
pubmed: 25677463
J Neurochem. 2008 Mar;104(6):1440-9
pubmed: 18221378
Anesthesiology. 2018 Aug;129(2):343-366
pubmed: 29462012
Genome Biol. 2014;15(12):550
pubmed: 25516281
Pain. 2008 Dec;140(3):436-45
pubmed: 18945547
Neuropharmacology. 2017 May 1;117:305-315
pubmed: 28237807
Nat Rev Neurosci. 2016 Dec 15;18(1):20-30
pubmed: 27974843
Nat Neurosci. 2017 Dec;20(12):1734-1743
pubmed: 29184209
J Neurosci. 2012 May 2;32(18):6351-63
pubmed: 22553040
Neurobiol Learn Mem. 2014 Nov;115:43-8
pubmed: 25150149
Trends Pharmacol Sci. 2010 Apr;31(4):153-60
pubmed: 20064669
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13656-61
pubmed: 14595021
Mol Pain. 2012 Dec 31;8:90
pubmed: 23272977
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8254-9
pubmed: 23630294
Science. 2014 Aug 1;345(6196):535-42
pubmed: 25082697
Eur J Neurosci. 2003 Mar;17(5):971-80
pubmed: 12653973
J Biol Chem. 2012 Aug 17;287(34):28966-74
pubmed: 22753418
Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):19977-82
pubmed: 23169654
Sci Signal. 2017 Mar 21;10(471):null
pubmed: 28325815
Cell Signal. 2006 Jun;18(6):771-82
pubmed: 16120478
Neuroscience. 2016 Dec 3;338:81-92
pubmed: 27189881
Neuron. 2015 Nov 18;88(4):762-73
pubmed: 26590347
J Neurosci. 2018 Aug 22;38(34):7529-7540
pubmed: 30054391
Eur J Neurosci. 2005 Jul;22(2):485-94
pubmed: 16045501
Pain. 2004 Dec;112(3):307-14
pubmed: 15561386
Nat Commun. 2012 Apr 24;3:791
pubmed: 22531176
Prog Mol Biol Transl Sci. 2009;86:299-333
pubmed: 20374720
J Neurosci. 2014 Oct 1;34(40):13505-15
pubmed: 25274827
Science. 2006 Jun 16;312(5780):1659-62
pubmed: 16778058
J Neurosci. 2015 Apr 22;35(16):6307-17
pubmed: 25904784
Neurosci Lett. 2011 Aug 21;501(1):31-4
pubmed: 21741448
Mol Pain. 2017 Jan;13:1744806917697009
pubmed: 28326943
J Neurochem. 2002 Aug;82(4):828-38
pubmed: 12358788
J Neurosci. 1997 Oct 15;17(20):8024-37
pubmed: 9315921
J Neurosci. 2019 Jan 16;39(3):393-411
pubmed: 30459229
Biol Psychiatry. 2018 Apr 15;83(8):648-656
pubmed: 29275841
Cell Signal. 2007 Apr;19(4):723-30
pubmed: 17126529
Neuropharmacology. 2015 Oct;97:464-75
pubmed: 26071110
Ann N Y Acad Sci. 2000;909:12-24
pubmed: 10911921
Neuron. 2008 Apr 24;58(2):238-47
pubmed: 18439408
Pain. 2018 Aug;159(8):1641-1651
pubmed: 29697531
J Physiol. 2007 Apr 1;580(Pt 1):51-65
pubmed: 17185339
Nat Neurosci. 2006 Jun;9(6):832-42
pubmed: 16699510
Mol Pain. 2009 Jan 27;5:4
pubmed: 19171071
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
J Neurosci. 2013 Apr 24;33(17):7574-82
pubmed: 23616562
Exp Neurol. 2016 Dec;286:1-11
pubmed: 27641322
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E2085-E2094
pubmed: 29440403
Biol Psychiatry. 2010 Apr 15;67(8):761-9
pubmed: 19914603
Neuron. 2014 Oct 1;84(1):123-136
pubmed: 25242222
J Neurosci. 1999 May 15;19(10):3674-80
pubmed: 10233999
J Comp Neurol. 1983 Mar 20;215(1):63-77
pubmed: 6853766
Neuron. 2010 Apr 15;66(1):149-60
pubmed: 20399736
Sci Rep. 2014 Oct 22;4:6719
pubmed: 25335491
Neuropharmacology. 2018 Mar 15;131:403-413
pubmed: 29339292
Trends Neurosci. 2009 Dec;32(12):611-8
pubmed: 19781793
Mol Pharmacol. 2016 Feb;89(2):273-86
pubmed: 26655302
J Neurophysiol. 1981 Mar;45(3):443-66
pubmed: 6783739
Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):E5088-97
pubmed: 26305935
Biochem Biophys Res Commun. 2005 Sep 16;335(1):132-8
pubmed: 16055088
Neuron. 2015 Aug 5;87(3):474-91
pubmed: 26247858