title: Reactive oxygen species are involved in group I mGluR-mediated facilitation of nociceptive processing in amygdala neurons.
abstract: Recent biochemical and behavioral data implicate reactive oxygen species (ROS) in peripheral and spinal pain mechanisms. However, pain-related functions of ROS in the brain and mechanisms of pain-related ROS activation remain to be determined. Our previous studies showed that the amygdala plays a key role in emotional-affective pain responses and pain modulation. Hyperactivity of amygdala neurons in an animal pain model depends on group I metabotropic glutamate receptors (subtypes mGluR1 and mGluR5), but their signaling pathway remains to be determined. Here we tested the hypothesis that activation of group I mGluRs increases nociceptive processing in amygdala neurons through a mechanism that involves ROS. Extracellular single-unit recordings were made from neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC) in anesthetized adult male rats. Administration of a group I mGluR agonist (DHPG) into the CeLC by microdialysis increased the responses to innocuous and noxious somatosensory (knee joint compression) and visceral (colorectal distention [CRD]) stimuli. A ROS scavenger (PBN) and a superoxide dismutase mimetic (TEMPOL) reversed the facilitatory effects of DHPG. An mGluR5 antagonist (MPEP) also inhibited the effects of DHPG on the responses to innocuous and noxious somatosensory and visceral stimuli, whereas an mGluR1 antagonist (LY367385) decreased only the responses to visceral stimulation. The results show for the first time that ROS mediate group I mGluR-induced facilitation of nociceptive processing in amygdala neurons. The antagonist data may suggest differential contributions of subtypes mGluR1 and mGluR5 to the processing of somatosensory and visceral nociceptive information in the amygdala.
authors.affiliation: Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
authors.forename: Guangchen
authors.initials: G
authors.lastname: Ji
authors.forename: Volker
authors.initials: V
authors.lastname: Neugebauer
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D016166:Free Radical Scavengers / Q000494:pharmacology; D006614:Hindlimb / Q000502:physiology; D007596:Joints / Q000502:physiology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012007:Rectum / Q000502:physiology; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D018094:Receptors, Metabotropic Glutamate; D013113:Spin Labels; C104077:metabotropic glutamate receptor type 1; D009569:Nitric Oxide; D008734:Methoxyhydroxyphenylglycol; D011493:Protein Kinase C; C001803:tempol; C010117:3,4-dihydroxyphenylglycol
references.citation: J Comp Neurol. 2004 Jan 1;468(1):24-56
references.pmid: 14648689
references.citation: Cell Mol Life Sci. 2000 Aug;57(8-9):1287-305
references.pmid: 11028919
references.citation: J Neurophysiol. 2009 Oct;102(4):2253-64
references.pmid: 19625541
references.citation: Pain. 2009 Jan;141(1-2):135-42
references.pmid: 19059721
references.citation: Mol Pain. 2010 Feb 08;6:10
references.pmid: 20144185
references.citation: J Med Chem. 2003 Jan 16;46(2):204-6
references.pmid: 12519057
references.citation: J Neurosci Res. 2002 Oct 1;70(1):1-7
references.pmid: 12237859
references.citation: Brain Res. 2003 Mar 21;966(2):253-64
references.pmid: 12618348
references.citation: J Neurophysiol. 2004 Jul;92(1):1-9
references.pmid: 15212433
references.citation: Brain Res. 2001 Mar 2;893(1-2):135-42
references.pmid: 11223001
references.citation: J Neurosci. 1991 Mar;11(3):852-68
references.pmid: 1705972
references.citation: J Physiol. 2007 Dec 15;585(Pt 3):741-58
references.pmid: 17947304
references.citation: Neurogastroenterol Motil. 2005 Aug;17(4):548-56
references.pmid: 16078944
references.citation: Am J Gastroenterol. 2002 Mar;97(3):654-61
references.pmid: 11926209
references.citation: J Neurosci. 1995 Oct;15(10):6377-88
references.pmid: 7472402
references.citation: Eur J Neurosci. 2003 Oct;18(8):2343-50
references.pmid: 14622196
references.citation: Brain Res. 1995 Oct 9;695(1):92-5
references.pmid: 8574654
references.citation: Neuron. 2005 Sep 15;47(6):787-93
references.pmid: 16157274
references.citation: J Comp Neurol. 1995 Oct 2;360(4):555-70
references.pmid: 8801249
references.citation: Pain. 2002 Jan;95(1-2):93-102
references.pmid: 11790471
references.citation: Neuron. 2005 Oct 20;48(2):175-87
references.pmid: 16242399
references.citation: Brain Res Rev. 2009 Apr;60(1):226-42
references.pmid: 19162070
references.citation: J Neurophysiol. 1996 Oct;76(4):2661-74
references.pmid: 8899636
references.citation: Pain. 2007 Jan;127(1-2):161-72
references.pmid: 17055162
references.citation: Mol Interv. 2004 Oct;4(5):248-50
references.pmid: 15471906
references.citation: Nat Rev Neurosci. 2004 Jul;5(7):565-75
references.pmid: 15208698
references.citation: J Neurosci. 2008 Apr 9;28(15):3861-76
references.pmid: 18400885
references.citation: J Neurophysiol. 2003 Mar;89(3):1343-52
references.pmid: 12626615
references.citation: J Physiol. 2005 May 1;564(Pt 3):907-21
references.pmid: 15760935
references.citation: J Neurosci. 2005 Nov 16;25(46):10717-28
references.pmid: 16291945
references.citation: Pain. 2005 Jun;115(3):398-409
references.pmid: 15911167
references.citation: J Neurophysiol. 2004 Jan;91(1):13-24
references.pmid: 13679408
references.citation: FEBS J. 2006 Feb;273(3):433-50
references.pmid: 16420469
references.citation: Cell Calcium. 2007 May;41(5):491-502
references.pmid: 17074386
references.citation: Gastroenterology. 2003 Jun;124(7):1738-47
references.pmid: 12806606
references.citation: J Neurosci. 2009 Jan 7;29(1):159-68
references.pmid: 19129394
references.citation: Pain. 2000 Jul;87(1):83-88
references.pmid: 10863048
references.citation: Physiol Rev. 2010 Apr;90(2):419-63
references.pmid: 20393190
references.citation: Pain. 2002 Apr;96(3):221-225
references.pmid: 11972993
references.citation: J Neurosci. 2006 Apr 12;26(15):3933-41
references.pmid: 16611809
references.citation: Neuroreport. 2009 Oct 28;20(16):1424-8
references.pmid: 19794317
references.citation: Gut. 2004 Nov;53(11):1595-601
references.pmid: 15479679
references.citation: Physiol Rev. 2003 Jul;83(3):803-34
references.pmid: 12843409
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1622-9
references.pmid: 17347454
references.citation: Behav Brain Res. 2007 Jul 19;181(1):163-7
references.pmid: 17481745
references.citation: Neurosci Lett. 1996 Sep 13;215(3):165-8
references.pmid: 8899739
references.citation: Pain. 2006 May;122(1-2):53-62
references.pmid: 16524661
references.citation: Pain. 2007 Dec 15;133(1-3):9-17
references.pmid: 17379413
references.citation: Brain Res. 1992 Jan 31;571(1):26-34
references.pmid: 1611493
references.citation: Mol Pain. 2007 Jun 05;3:13
references.pmid: 17550594
references.citation: Biochemistry. 2002 Jun 18;41(24):7743-50
references.pmid: 12056906
references.citation: Neurogastroenterol Motil. 2004 Oct;16(5):575-87
references.pmid: 15500514
references.citation: Pain. 2004 Jul;110(1-2):299-309
references.pmid: 15275780
references.citation: Neuroreport. 1996 May 31;7(8):1382-4
references.pmid: 8856680
references.citation: Eur J Neurosci. 2003 Nov;18(9):2433-48
references.pmid: 14622144
references.citation: Biochim Biophys Acta. 2004 Dec 6;1742(1-3):119-31
references.pmid: 15590062
references.citation: J Neurosci. 2007 Feb 14;27(7):1543-51
references.pmid: 17301163
references.citation: J Neurosci. 1996 Feb 15;16(4):1324-36
references.pmid: 8778284
references.citation: Neurosci Lett. 2003 Jul 3;344(3):197-200
references.pmid: 12812839
references.citation: Antioxid Redox Signal. 1999 Winter;1(4):481-99
references.pmid: 11233146
references.citation: Pain. 2005 Jan;113(1-2):211-22
references.pmid: 15621382
references.citation: Neuroscientist. 2004 Jun;10(3):221-34
references.pmid: 15155061
references.citation: Neurosci Lett. 2004 May 6;361(1-3):254-7
references.pmid: 15135941
references.citation: J Neurophysiol. 1994 May;71(5):1646-60
references.pmid: 8064340
references.citation: J Neurophysiol. 2008 Mar;99(3):1565-71
references.pmid: 18199822
references.citation: J Neurophysiol. 2003 Oct;90(4):2180-9
references.pmid: 12815023
references.citation: Neuron. 2007 Aug 2;55(3):377-91
references.pmid: 17678852
references.citation: Pain. 2007 Oct;131(3):262-271
references.pmid: 17317010
references.citation: Antioxid Redox Signal. 2007 Feb;9(2):233-44
references.pmid: 17115936
references.citation: Neuron. 2005 Sep 15;47(6):783-6
references.pmid: 16157273
references.citation: Mol Pain. 2008 Jul 16;4:26
references.pmid: 18631385
references.citation: J Neurosci. 2002 Mar 15;22(6):2135-41
references.pmid: 11896153
references.citation: J Biol Chem. 2009 Jun 5;284(23):15629-39
references.pmid: 19364772
references.citation: Pain. 2008 Sep 15;138(3):514-524
references.pmid: 18375065
references.citation: Neuroimage. 2009 Jan 1;44(1):23-34
references.pmid: 18722538
references.citation: J Neurophysiol. 2007 Jun;97(6):3893-904
references.pmid: 17392412
references.citation: J Neurophysiol. 2002 Sep;88(3):1185-96
references.pmid: 12205140
references.citation: Br J Pharmacol. 2003 Mar;138(6):1026-30
references.pmid: 12684257
references.citation: PLoS One. 2010 Jan 05;5(1):e8573
references.pmid: 20052291
references.citation: Neurosci Lett. 2002 Sep 20;330(2):127-30
references.pmid: 12231428
references.citation: Pain. 2003 May;103(1-2):83-91
references.pmid: 12749962
references.citation: J Neurophysiol. 2005 Sep;94(3):1659-63
references.pmid: 16105951
references.citation: CNS Drug Rev. 2006 Summer;12(2):149-66
references.pmid: 16958988
references.citation: J Neurophysiol. 2003 Feb;89(2):716-27
references.pmid: 12574449
references.citation: Pain. 2004 Sep;111(1-2):116-24
references.pmid: 15327815
references.citation: J Neurophysiol. 2009 Jul;102(1):244-58
references.pmid: 19369360
references.citation: J Neurophysiol. 2008 Mar;99(3):1201-12
references.pmid: 18171711
references.citation: J Neurophysiol. 2003 Jul;90(1):2-11
references.pmid: 12634272
references.citation: J Neurosci. 2003 Jan 1;23(1):52-63
references.pmid: 12514201
references.citation: J Neurophysiol. 1993 Feb;69(2):557-68
references.pmid: 8459286
references.citation: J Neurophysiol. 1998 Jul;80(1):452-7
references.pmid: 9658063
references.citation: Science. 2009 Aug 7;325(5941):760-4
references.pmid: 19661434
references.citation: Pain. 2003 Jul;104(1-2):249-57
references.pmid: 12855335
references.citation: Neuropharmacology. 2008 Sep;55(4):537-45
references.pmid: 18533199
references.citation: J Pharmacol Exp Ther. 2004 Jun;309(3):869-78
references.pmid: 14988418
references.citation: J Neurophysiol. 2002 Jan;87(1):103-12
references.pmid: 11784733
references.citation: Handb Exp Pharmacol. 2007;(177):217-49
references.pmid: 17087125
references.citation: Mol Pain. 2008 Jun 23;4:24
references.pmid: 18573207
references.citation: Pain. 2007 Jan;127(1-2):17-26
references.pmid: 16965855
references.citation: Gastroenterology. 2002 Oct;123(4):1216-25
references.pmid: 12360483
references.citation: Pain. 2004 Jul;110(1-2):112-22
references.pmid: 15275758
references.citation: Ageing Res Rev. 2004 Nov;3(4):431-43
references.pmid: 15541710
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7675-9
references.pmid: 10393879
references.citation: J Neurophysiol. 2010 Jan;103(1):382-91
references.pmid: 19906875
references.citation: Brain Res. 2006 Feb 3;1071(1):91-6
references.pmid: 16423333