title: Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors.
abstract: BACKGROUND
  Group I metabotropic glutamate receptor (mGluR1/5) signaling is an important mechanism of pain-related plasticity in the amygdala that plays a key role in the emotional-affective dimension of pain. Homer1a, the short form of the Homer1 family of scaffolding proteins, disrupts the mGluR-signaling complex and negatively regulates nociceptive plasticity at spinal synapses. Using transgenic mice overexpressing Homer1a in the forebrain (H1a-mice), we analyzed synaptic plasticity, pain behavior and mGluR1 function in the basolateral amygdala (BLA) in a model of arthritis pain.
  
  
  RESULTS
  In contrast to wild-type mice, H1a-mice mice did not develop increased pain behaviors (spinal reflexes and audible and ultrasonic vocalizations) after induction of arthritis in the knee joint. Whole-cell patch-clamp recordings in brain slices showed that excitatory synaptic transmission from the BLA to the central nucleus (CeA) did not change in arthritic H1a-mice but increased in arthritic wild-type mice. A selective mGluR1 antagonist (CPCCOEt) had no effect on enhanced synaptic transmission in slices from H1a-BLA mice with arthritis but inhibited transmission in wild-type mice with arthritis as in our previous studies in rats.
  
  
  CONCLUSIONS
  The results show that Homer1a expressed in forebrain neurons, prevents the development of pain hypersensitivity in arthritis and disrupts pain-related plasticity at synapses in amygdaloid nuclei. Furthermore, Homer1a eliminates the effect of an mGluR1 antagonist, which is consistent with the well-documented disruption of mGluR1 signaling by Homer1a. These findings emphasize the important role of mGluR1 in pain-related amygdala plasticity and provide evidence for the involvement of Homer1 proteins in the forebrain in the modulation of pain hypersensitivity.
authors: Department of Neuroscience & Cell Biology, The University of Texas Medical Branch, 301 University Blvd, Galveston, Texas 77555-1069, USA.
authors: Anke
authors: A
authors: Tappe-Theodor
authors: Yu
authors: Y
authors: Fu
authors: Rohini
authors: R
authors: Kuner
authors: Volker
authors: V
authors: Neugebauer
references: Mol Pain. 2010 Feb 08;6:10
references: 20144185
references: J Neurochem. 2002 May;81(3):407-13
references: 12065649
references: Trends Neurosci. 2000 Feb;23(2):80-8
references: 10652549
references: Annu Rev Pharmacol Toxicol. 2010;50:295-322
references: 20055706
references: Prog Neurobiol. 1999 Sep;59(1):55-79
references: 10416961
references: J Neurosci Methods. 2005 Feb 15;141(2):261-9
references: 15661308
references: J Neurosci. 2011 Jan 19;31(3):1114-27
references: 21248136
references: Ann Clin Lab Sci. 2009 Winter;39(1):71-5
references: 19201745
references: Anesth Analg. 2009 Dec;109(6):2000-7
references: 19923532
references: Mol Pain. 2010 Dec 16;6:93
references: 21162731
references: J Neurosci. 2003 Jan 1;23(1):52-63
references: 12514201
references: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):774-9
references: 16407107
references: Curr Opin Neurobiol. 2000 Jun;10(3):370-4
references: 10851183
references: Neuropharmacology. 2011 Jun;60(7-8):1017-41
references: 21036182
references: Brain Res Rev. 2009 Apr;60(1):226-42
references: 19162070
references: Science. 2010 Dec 3;330(6009):1400-4
references: 21127255
references: J Neurosci. 2008 Apr 9;28(15):3861-76
references: 18400885
references: Nat Med. 2006 Jun;12(6):677-81
references: 16715092
references: J Physiol. 2005 May 1;564(Pt 3):907-21
references: 15760935
references: Nature. 1997 Mar 20;386(6622):284-8
references: 9069287
references: J Neurosci. 2005 Nov 16;25(46):10717-28
references: 16291945
references: J Neurophysiol. 2004 Jan;91(1):13-24
references: 13679408
references: J Neurosci. 2007 Feb 14;27(7):1543-51
references: 17301163
references: Neurosci Lett. 2006 May 8;398(3):296-9
references: 16448751
references: Pain. 2005 Jan;113(1-2):211-22
references: 15621382
references: J Biol Chem. 1998 Sep 11;273(37):23969-75
references: 9727012
references: Neuroscientist. 2004 Jun;10(3):221-34
references: 15155061
references: Brain Res Brain Res Rev. 1999 Jan;29(1):83-120
references: 9974152
references: Neuron. 1998 Oct;21(4):717-26
references: 9808459
references: Neuron. 1998 Oct;21(4):707-16
references: 9808458
references: Mol Pain. 2008 Jul 16;4:26
references: 18631385
references: Mol Pain. 2007 Mar 28;3:8
references: 17391515
references: J Neurophysiol. 2010 Jul;104(1):218-29
references: 20463194
references: Neuropharmacology. 2008 Sep;55(4):537-45
references: 18533199
references: J Neurosci. 2010 Jun 16;30(24):8203-13
references: 20554871