title: Activity-dependent modulation of glutamatergic signaling in the developing rat dorsal horn by early tissue injury.
abstract: Tissue injury in early life can produce distinctive effects on pain processing, but little is known about the underlying neural mechanisms. Neonatal inflammation modulates excitatory synapses in spinal nociceptive circuits, but it is unclear whether this results directly from altered afferent input. Here we investigate excitatory and inhibitory synaptic transmission in the rat superficial dorsal horn following neonatal hindlimb surgical incision using in vitro patch-clamp recordings and test the effect of blocking peripheral nerve activity on the injury-evoked changes. Surgical incision through the skin and muscle of the hindlimb at postnatal day 3 (P3) or P10 selectively increased the frequency, but not amplitude, of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) recorded 2-3 days after injury, without altering miniature inhibitory postsynaptic current frequency or amplitude at this time point. Meanwhile, incision at P17 failed to affect excitatory or inhibitory synaptic function at 2-3 days postinjury. The elevated mEPSC frequency was accompanied by increased inward rectification of evoked alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated currents, but no change in AMPAR/N-methyl-D-aspartate receptor ratios, and was followed by a persistent reduction in mEPSC frequency by 9-10 days postinjury. Prolonged blockade of primary afferent input from the time of injury was achieved by administration of bupivacaine hydroxide or tetrodotoxin to the sciatic nerve at P3. The increase in mEPSC frequency evoked by P3 incision was prevented by blocking sciatic nerve activity. These results demonstrate that increased afferent input associated with peripheral tissue injury selectively modulates excitatory synaptic drive onto developing spinal sensory neurons and that the enhanced glutamatergic signaling in the dorsal horn following neonatal surgical incision is activity dependent.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Suellen M
authors.initials: SM
authors.lastname: Walker
authors.forename: Maria
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: Mark L
authors.initials: ML
authors.lastname: Baccei
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002045:Bupivacaine / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000293:injuries*; D009407:Nerve Block; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D013779:Tetrodotoxin; D002045:Bupivacaine
references.citation: J Neurosci. 2008 May 21;28(21):5494-503
references.pmid: 18495883
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9298-302
references.pmid: 7568121
references.citation: Pain. 2006 Dec 5;125(3):278-285
references.pmid: 17011707
references.citation: J Neurosci. 2003 Aug 20;23(20):7719-25
references.pmid: 12930812
references.citation: Nature. 1998 Jun 18;393(6686):695-8
references.pmid: 9641681
references.citation: J Neurosci. 1999 Jan 15;19(2):859-67
references.pmid: 9880605
references.citation: Mol Pain. 2009 Mar 02;5:10
references.pmid: 19254372
references.citation: Nature. 2003 Aug 21;424(6951):938-42
references.pmid: 12931188
references.citation: Neuron. 1995 Aug;15(2):453-62
references.pmid: 7646897
references.citation: Neuron. 1997 Feb;18(2):269-80
references.pmid: 9052797
references.citation: J Neurophysiol. 2007 Sep;98(3):1057-63
references.pmid: 17567772
references.citation: Science. 2000 Jul 28;289(5479):628-31
references.pmid: 10915627
references.citation: J Neurosci. 2005 Oct 19;25(42):9613-23
references.pmid: 16237166
references.citation: J Neurosci. 1998 Nov 1;18(21):8740-50
references.pmid: 9786981
references.citation: Neuron. 2006 Mar 2;49(5):663-70
references.pmid: 16504942
references.citation: Neurosci Lett. 1982 Jun 30;30(3):315-20
references.pmid: 6287371
references.citation: Neuroscience. 1993 Mar;53(2):519-26
references.pmid: 8098516
references.citation: Anesthesiology. 2008 Oct;109(4):698-706
references.pmid: 18813050
references.citation: J Neurophysiol. 2006 Mar;95(3):1656-68
references.pmid: 16492946
references.citation: Nature. 1996 Jun 27;381(6585):793-6
references.pmid: 8657283
references.citation: Acta Physiol Scand Suppl. 1974;406:1-55
references.pmid: 4526498
references.citation: Pain. 2004 Aug;110(3):588-596
references.pmid: 15288399
references.citation: J Physiol. 2003 Apr 1;548(Pt 1):131-8
references.pmid: 12576493
references.citation: Pain. 1989 Oct;39(1):31-36
references.pmid: 2812853
references.citation: J Neuropathol Exp Neurol. 1968 Oct;27(4):546-70
references.pmid: 4879906
references.citation: Anesthesiology. 1986 Jan;64(1):29-35
references.pmid: 3942334
references.citation: J Neurosci. 2009 Jan 21;29(3):686-95
references.pmid: 19158295
references.citation: Neuron. 2005 Jul 7;47(1):101-14
references.pmid: 15996551
references.citation: Pain. 1998 Sep;77(3):305-313
references.pmid: 9808356
references.citation: J Neurosci Methods. 2005 Feb 15;141(2):199-205
references.pmid: 15661301
references.citation: Neuroscience. 2008 Mar 18;152(2):502-10
references.pmid: 18262726
references.citation: Pain. 2008 Mar;135(1-2):119-30
references.pmid: 17590272
references.citation: Pain. 1999 Jul;82(1):33-38
references.pmid: 10422657
references.citation: J Neurosci. 2005 Apr 13;25(15):3900-7
references.pmid: 15829642
references.citation: Eur J Pain. 2007 Oct;11(7):799-809
references.pmid: 17320438
references.citation: Gene Expr. 1999;7(4-6):321-35
references.pmid: 10440233
references.citation: Pain. 2003 Sep;105(1-2):185-95
references.pmid: 14499435
references.citation: Pain. 1992 Oct;51(1):81-90
references.pmid: 1454409
references.citation: J Comp Neurol. 1984 Jul 10;226(4):508-22
references.pmid: 6747032
references.citation: J Physiol. 2008 Jan 15;586(2):515-27
references.pmid: 18033811
references.citation: Neuroreport. 2001 Feb 12;12(2):399-403
references.pmid: 11209957
references.citation: Anesthesiology. 2003 Aug;99(2):443-8
references.pmid: 12883418
references.citation: J Neurophysiol. 2000 Feb;83(2):955-62
references.pmid: 10669507
references.citation: Can J Physiol Pharmacol. 1983 Dec;61(12):1478-82
references.pmid: 6200194
references.citation: J Physiol. 2003 May 15;549(Pt 1):231-42
references.pmid: 12679376
references.citation: Nat Neurosci. 2009 Jun;12(6):751-8
references.pmid: 19430474
references.citation: J Neurophysiol. 2006 Aug;96(2):579-90
references.pmid: 16611846
references.citation: J Neurosci. 2003 Sep 24;23(25):8752-8
references.pmid: 14507975
references.citation: J Neurosci. 2004 May 19;24(20):4749-57
references.pmid: 15152035
references.citation: Pain. 2005 Aug;116(3):243-256
references.pmid: 15964687
references.citation: Neuron. 2001 Jan;29(1):157-69
references.pmid: 11182088
references.citation: Science. 1991 May 10;252(5007):851-3
references.pmid: 1709304
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15518-23
references.pmid: 15492224
references.citation: J Neurophysiol. 2002 Mar;87(3):1311-7
references.pmid: 11877505
references.citation: Pain. 2009 May;143(1-2):56-64
references.pmid: 19249156
references.citation: J Physiol. 2002 Apr 1;540(Pt 1):189-207
references.pmid: 11927679
references.citation: J Neurosci. 2006 Feb 8;26(6):1787-94
references.pmid: 16467527
references.citation: J Physiol. 2009 Jun 15;587(Pt 12):2927-35
references.pmid: 19403624
references.citation: J Physiol. 1979 Dec;297(0):479-91
references.pmid: 94092
references.citation: J Neurosci. 1997 Dec 15;17(24):9393-406
references.pmid: 9390995
references.citation: Brain Res. 1986 Jan;389(1-2):261-70
references.pmid: 3948011
references.citation: Pain. 2009 Jan;141(1-2):79-87
references.pmid: 19026489
references.citation: J Comp Neurol. 2008 Jun 1;508(4):592-604
references.pmid: 18383051
references.citation: Mol Pain. 2005 Sep 22;1:27
references.pmid: 16179088
references.citation: Neuron. 2005 Feb 17;45(4):563-73
references.pmid: 15721242
references.citation: Anesthesiology. 2007 Jun;106(6):1204-12
references.pmid: 17525596
references.citation: Neuroscience. 2003;122(3):799-805
references.pmid: 14622922
references.citation: J Physiol. 1996 Dec 1;497 ( Pt 2):457-72
references.pmid: 8961187
references.citation: J Neurosci. 1998 Aug 15;18(16):6558-67
references.pmid: 9698343
references.citation: Neuron. 2004 Nov 18;44(4):637-50
references.pmid: 15541312
references.citation: Anesth Analg. 2002 Feb;94(2):319-24, table of contents
references.pmid: 11812691
references.citation: J Neurosci. 2002 Aug 1;22(15):6724-31
references.pmid: 12151551
references.citation: Pain. 2007 Nov;132 Suppl 1:S124-S133
references.pmid: 17904745
references.citation: J Neurosci. 2002 Sep 15;22(18):8084-90
references.pmid: 12223562
references.citation: Eur J Neurosci. 2002 Oct;16(7):1249-58
references.pmid: 12405985
references.citation: Science. 2004 May 7;304(5672):884-7
references.pmid: 15131310