title: Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception.
abstract: Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus.
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Henning Matthias
authors.initials: HM
authors.lastname: Reimann
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hentschel
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Marek
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Huelnhagen
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kox
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Sonia
authors.initials: S
authors.lastname: Waiczies
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Russ
authors.initials: R
authors.lastname: Hodge
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pohlmann
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany.|Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Niendorf
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001931:Brain Mapping; D005240:Feasibility Studies; D006321:Heart / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010812:Physical Stimulation; D013696:Temperature
chemical_list: D010100:Oxygen
references.citation: Anesth Analg. 1994 Jul;79(1):58-65
references.pmid: 8010455
references.citation: Neuroimage. 2011 Feb 1;54(3):2237-49
references.pmid: 20932917
references.citation: J Cell Physiol. 1998 Oct;177(1):137-47
references.pmid: 9731754
references.citation: Neuroimage. 2013 Apr 15;70:288-300
references.pmid: 23275046
references.citation: Neuroimage. 2012 Aug 15;62(2):782-90
references.pmid: 21979382
references.citation: J Neurosci Methods. 2010 Jun 15;189(2):233-45
references.pmid: 20381530
references.citation: J Cereb Blood Flow Metab. 2012 Jul;32(7):1188-206
references.pmid: 22395207
references.citation: Neuroimage. 2010 Jun;51(2):704-12
references.pmid: 20211267
references.citation: Int J Neurosci. 1995 Mar;81(1-2):111-22
references.pmid: 7775066
references.citation: J Neurosci Methods. 2012 Feb 15;204(1):9-18
references.pmid: 22068031
references.citation: Pain. 2009 Jun;143(3):161-2
references.pmid: 19339115
references.citation: PLoS One. 2013;8(10):e76655
references.pmid: 24146902
references.citation: J Neurophysiol. 1978 Mar;41(2):509-28
references.pmid: 418156
references.citation: Pain. 2013 Aug;154(8):1434-41
references.pmid: 23707276
references.citation: Prog Brain Res. 1976;43:263-77
references.pmid: 815956
references.citation: Ann Med. 1995 Apr;27(2):213-6
references.pmid: 7632416
references.citation: PLoS One. 2015;10(5):e0126513
references.pmid: 25950440
references.citation: Neuroreport. 2010 Jan 6;21(1):29-33
references.pmid: 19934782
references.citation: Eur J Neurosci. 2009 Jul;30(2):242-50
references.pmid: 19659924
references.citation: Neuroimage. 2010 Nov 1;53(2):365-72
references.pmid: 20600960
references.citation: Pain. 2005 Jul;116(1-2):1-3
references.pmid: 15936889
references.citation: Neurosci Lett. 2012 Jun 29;520(2):131-9
references.pmid: 22445887
references.citation: Magn Reson Imaging. 2002 Dec;20(10):707-12
references.pmid: 12591566
references.citation: J Physiol. 2000 Nov 1;528(Pt 3):539-49
references.pmid: 11060130
references.citation: Cancer Res. 2011 Jun 1;71(11):3872-80
references.pmid: 21512134
references.citation: Pain. 2010 Dec;151(3):655-63
references.pmid: 20851520
references.citation: Neuroimage. 2008 Jun;41(2):286-301
references.pmid: 18407525
references.citation: Neuron. 1998 Sep;21(3):531-43
references.pmid: 9768840
references.citation: Prog Neurobiol. 2012 Feb;96(2):208-19
references.pmid: 22270045
references.citation: Pain. 2003 Sep;105(1-2):57-64
references.pmid: 14499420
references.citation: Contemp Top Lab Anim Sci. 2004 Sep;43(5):13-8
references.pmid: 15461434
references.citation: Exp Brain Res. 2010 Aug;205(1):1-12
references.pmid: 20607220
references.citation: Int J Hyperthermia. 2011;27(4):320-43
references.pmid: 21591897
references.citation: ILAR J. 2011;52(3):e21-31
references.pmid: 21677360
references.citation: NMR Biomed. 2011 May;24(4):439-46
references.pmid: 22945293
references.citation: Prog Neurobiol. 2011 Jan;93(1):111-24
references.pmid: 21040755
references.citation: Pain. 2011 Feb;152(2):428-39
references.pmid: 21196078
references.citation: Ind Health. 2002 Oct;40(4):353-61
references.pmid: 12502238
references.citation: Brain Struct Funct. 2016 Mar;221(2):941-54
references.pmid: 25445840
references.citation: Pain. 2013 Mar;154(3):334-44
references.pmid: 23245864
references.citation: Mol Pain. 2010;6:27
references.pmid: 20465845
references.citation: Biull Eksp Biol Med. 1994 Aug;118(8):120-2
references.pmid: 7949024
references.citation: Magn Reson Med. 2003 Feb;49(2):264-70
references.pmid: 12541246
references.citation: Neuroimage. 2010 Jul 15;51(4):1367-77
references.pmid: 20350606
references.citation: Neuroimage. 2013 Sep;78:196-203
references.pmid: 23587687
references.citation: Neurosci Biobehav Rev. 2011 Apr;35(5):1125-43
references.pmid: 21126534
references.citation: Neurosci Biobehav Rev. 2010 Feb;34(2):177-84
references.pmid: 19822171
references.citation: Nature. 1996 Nov 21;384(6606):258-60
references.pmid: 8918874
references.citation: J Magn Reson Imaging. 2010 Jan;31(1):192-203
references.pmid: 20027588
references.citation: PLoS One. 2012;7(5):e36699
references.pmid: 22629325
references.citation: Acta Anaesthesiol Taiwan. 2013 Jun;51(2):73-80
references.pmid: 23968658
references.citation: Somatosens Mot Res. 2007 Dec;24(4):189-201
references.pmid: 18097992
references.citation: Neurosci Lett. 1997 May 16;227(2):95-8
references.pmid: 9180212
references.citation: Brain. 1992 Apr;115 ( Pt 2):607-21
references.pmid: 1606484
references.citation: Neuroimage. 2009 Jul 1;46(3):786-802
references.pmid: 19195496
references.citation: Pain. 2007 Dec 5;132(3):301-11
references.pmid: 17533117
references.citation: J Neurosci. 2003 Jun 1;23(11):4766-74
references.pmid: 12805316
references.citation: Med Eng Phys. 2008 Oct;30(8):953-8
references.pmid: 18243035
references.citation: Neuroimage. 2001 Oct;14(4):891-8
references.pmid: 11554808
references.citation: Neuroimage. 2012 Aug 15;62(2):648-51
references.pmid: 21945795
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3731-6
references.pmid: 21245297
references.citation: Neuroimage. 2011 Jan 15;54(2):1355-66
references.pmid: 20817102
references.citation: Stat Methods Med Res. 2003 Oct;12(5):419-46
references.pmid: 14599004
references.citation: Funct Neurol. 1988 Apr-Jun;3(2):157-66
references.pmid: 3402815
references.citation: Exp Brain Res. 1983;51(2):283-90
references.pmid: 6617797
references.citation: Neuron. 2001 Dec 6;32(5):927-46
references.pmid: 11738036
references.citation: Nat Protoc. 2009;4(2):174-96
references.pmid: 19180088
references.citation: J Pain. 2010 May;11(5):408-19
references.pmid: 20075013
references.citation: Exp Brain Res. 2013 Mar;225(3):339-48
references.pmid: 23423165
references.citation: Front Neuroinform. 2013 Dec 23;7:39
references.pmid: 24409140
references.citation: Front Neuroanat. 2008 Apr 17;2:1
references.pmid: 18958199
references.citation: Magn Reson Imaging. 2007 Jul;25(6):826-33
references.pmid: 17451905
references.citation: Neuroimage. 2011 Feb 1;54(3):2033-44
references.pmid: 20851191
references.citation: Anesthesiology. 2000 Mar;92(3):699-707
references.pmid: 10719949
references.citation: Clin Neurophysiol. 2006 Jan;117(1):118-30
references.pmid: 16256426
references.citation: J Neurosci Methods. 2007 Jan 30;159(2):261-7
references.pmid: 16945419
references.citation: Exp Brain Res. 1983;49(2):174-80
references.pmid: 6832255
references.citation: J Neurophysiol. 1989 Nov;62(5):1028-38
references.pmid: 2585037
references.citation: Neuroimage. 2011 Jan 15;54(2):1324-35
references.pmid: 20851770
references.citation: Muscle Nerve. 2008 Nov;38(5):1498-505
references.pmid: 18932210
references.citation: Nat Neurosci. 2014 Oct;17(10):1304-12
references.pmid: 25254980
references.citation: Cell. 2010 Nov 12;143(4):628-38
references.pmid: 21074052
references.citation: Neuroimage. 2014 Jul 1;94:372-84
references.pmid: 24495809
references.citation: Pain. 2012 Jul;153(7):1450-8
references.pmid: 22575227
references.citation: Curr Biol. 2013 Feb 18;23(4):R164-76
references.pmid: 23428330
references.citation: Front Integr Neurosci. 2014 May 05;8:35
references.pmid: 24829554
references.citation: J Neural Transm (Vienna). 2011 Aug;118(8):1139-54
references.pmid: 21373762
references.citation: Neuroimage. 2011 Oct 1;58(3):732-40
references.pmid: 21704710
references.citation: J Neurophysiol. 2001 Apr;85(4):1561-74
references.pmid: 11287480
references.citation: Sci Transl Med. 2014 Aug 13;6(249):249sr3
references.pmid: 25122640
references.citation: J Am Assoc Lab Anim Sci. 2007 Sep;46(5):37-41
references.pmid: 17877326
references.citation: Pain. 1996 Jul;66(1):23-9
references.pmid: 8857628
references.citation: Neuroimage. 2011 Feb 14;54(4):2828-39
references.pmid: 20974263