Activation of hippocampal microglia in a murine model of cancer-induced pain.
Iba1
breast cancer
cancer-induced bone pain
hippocampus
nociception
Journal
Journal of pain research
ISSN: 1178-7090
Titre abrégé: J Pain Res
Pays: New Zealand
ID NLM: 101540514
Informations de publication
Date de publication:
2019
2019
Historique:
entrez:
3
4
2019
pubmed:
3
4
2019
medline:
3
4
2019
Statut:
epublish
Résumé
Pain is a common and debilitating comorbidity of metastatic breast cancer. The hippocampus has been implicated in nociceptive processing, particularly relating to the subjective aspect of pain. Here, a syngeneic mouse model was used to characterize the effects of peripheral tumors on hippocampal microglial activation in relation to cancer-induced pain (CIP). Mice were systemically treated with the colony-stimulating factor 1 receptor inhibitor Pexidartinib prior to intrafemoral (IF) or subcutaneous 4T1 carcinoma cell inoculation. Spontaneous and evoked nociceptive responses were quantitated throughout tumor development, and contralateral hippocampi were collected via endpoint microdissection for RNA analysis. Additionally, IF tumor-bearing animals were sacrificed on days 5, 10, 15, and 20 post 4T1 cell inoculation, and brain sections were immunofluorescently stained for Iba1, a marker of activated microglia. Ablation of these neuroimmune cells with the CSF1R inhibitor Pexidartinib delayed the onset and severity of cancer-induced nociceptive behaviors in IF tumor-bearing animals, adding to the body of literature that demonstrates microglial contribution to the development and maintenance of CIP. Furthermore, in untreated IF tumor-bearing mice, nociceptive behaviors appeared to progress in parallel with microglial activation in hippocampal regions. Immunofluorescent Iba1+ microglia increased in the dentate gyrus and cornu ammonis 1 hippocampal regions in IF tumor-bearing animals over time, which was confirmed at the mRNA level using relevant microglial markers. This is the first experimental evidence to demonstrate the effects of peripheral tumor-induced nociception on hippocampal microglial activation. The increase in hippocampal microglia observed in the present study may reflect the emotional and cognitive deficits reported by patients with CIP.
Identifiants
pubmed: 30936739
doi: 10.2147/JPR.S191860
pii: jpr-12-1003
pmc: PMC6430067
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1003-1016Déclaration de conflit d'intérêts
Disclosure The authors report no conflicts of interest in this work.
Références
Cancer Res. 2001 May 15;61(10):4038-47
pubmed: 11358823
Exp Neurol. 2001 Nov;172(1):92-9
pubmed: 11681843
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Ann N Y Acad Sci. 2001 Mar;933:265-77
pubmed: 12000027
Glia. 2002 Nov;40(2):140-55
pubmed: 12379902
Eur J Immunol. 1992 Sep;22(9):2429-36
pubmed: 1355433
Brain Res. 2004 Apr 9;1004(1-2):167-76
pubmed: 15033432
Neuroscience. 2004;125(4):981-93
pubmed: 15120858
Eur J Neurosci. 2004 Dec;20(11):3027-34
pubmed: 15579157
Pain. 1992 Apr;49(1):105-12
pubmed: 1594270
Pain. 2005 Nov;118(1-2):125-36
pubmed: 16154703
Behav Brain Res. 2006 Apr 3;168(2):221-5
pubmed: 16377002
Neurosci Lett. 1991 Dec 9;133(2):159-62
pubmed: 1687755
Nat Rev Neurosci. 2007 Jan;8(1):57-69
pubmed: 17180163
Eur J Pharmacol. 2007 May 7;562(1-2):39-46
pubmed: 17362915
Eur J Neurosci. 2007 Jul;26(2):446-50
pubmed: 17623020
Eur J Pharmacol. 2008 Mar 31;583(1):115-27
pubmed: 18289522
Eur J Pain. 2009 Feb;13(2):138-45
pubmed: 18499488
Life Sci. 2008 Nov 7;83(19-20):644-50
pubmed: 18854195
Nat Rev Immunol. 2008 Dec;8(12):958-69
pubmed: 19029990
Depress Anxiety. 2009;26(10):888-901
pubmed: 19691031
Mol Pain. 2009 Sep 22;5:55
pubmed: 19772643
Neurosci Bull. 2009 Oct;25(5):237-66
pubmed: 19784080
Neuroscience. 1990;39(1):151-70
pubmed: 2089275
Prog Neurobiol. 2011 Jan;93(1):111-24
pubmed: 21040755
J Affect Disord. 2011 Nov;134(1-3):483-7
pubmed: 21745692
Dev Neurosci. 2011;33(3-4):199-209
pubmed: 21757877
Pain. 2011 Nov;152(11):2564-74
pubmed: 21907491
Spine (Phila Pa 1976). 2012 May 15;37(11):E668-77
pubmed: 22146287
J Neurosci. 2012 Apr 25;32(17):5747-56
pubmed: 22539837
J Pharmacol Toxicol Methods. 2012 Jul;66(1):8-13
pubmed: 22575456
Brain Res. 2012 Jul 17;1465:1-9
pubmed: 22613229
Science. 2012 Oct 5;338(6103):72-5
pubmed: 23042885
PLoS One. 2012;7(10):e48367
pubmed: 23110234
Anat Rec (Hoboken). 2013 Mar;296(3):378-81
pubmed: 23382140
Nat Rev Neurosci. 2013 Jul;14(7):502-11
pubmed: 23719569
Prog Neurobiol. 2013 Oct;109:1-27
pubmed: 23827972
Pain. 2014 Jan;155(1):28-36
pubmed: 23999057
CNS Neurol Disord Drug Targets. 2013 Sep;12(6):773-84
pubmed: 24047523
Breast Cancer Res Treat. 2014 Jan;143(2):255-63
pubmed: 24337539
Neurosci Biobehav Rev. 2014 Feb;39:61-78
pubmed: 24374383
Brain Behav Immun. 2014 Feb;36:147-55
pubmed: 24513875
Neuron. 2014 Apr 16;82(2):380-97
pubmed: 24742461
Brain Res. 2015 Mar 2;1599:158-67
pubmed: 25555372
Mol Neurobiol. 2016 Mar;53(2):1181-94
pubmed: 25598354
Handb Exp Pharmacol. 2015;227:261-84
pubmed: 25846623
Neurosci Biobehav Rev. 2015 Jun;53:139-59
pubmed: 25857253
J Neurosci. 2015 May 20;35(20):7950-63
pubmed: 25995479
Nat Neurosci. 2015 Aug;18(8):1081-3
pubmed: 26120961
Behav Brain Res. 2015 Nov 1;294:25-35
pubmed: 26222786
Pain. 2016 Feb;157(2):418-28
pubmed: 26313405
Genes Brain Behav. 2016 Nov;15(8):711-721
pubmed: 27561409
J Neuroimmunol. 2017 Aug 15;309:12-22
pubmed: 28601280
Mol Pain. 2018 Jan-Dec;14:1744806918776467
pubmed: 29761734
Mol Pain. 2018 Jan-Dec;14:1744806918781733
pubmed: 29882480
Brain. 1978 Mar;101(1):83-117
pubmed: 638728
Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9
pubmed: 9630473