title: Transgene-mediated expression of tumor necrosis factor soluble receptor attenuates morphine tolerance in rats.
abstract: Opiate/narcotic analgesics are the most effective treatments for chronic severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. Recent evidence suggests chronic morphine may activate glial cells to release proinflammatory cytokines. In this study, we used herpes simplex virus (HSV) vector-based gene transfer to dorsal root ganglion to produce a local release of p55 tumor necrosis factor (TNF) soluble receptor in the spinal cord in rats with morphine tolerance. Subcutaneous inoculation of HSV vectors expressing p55 TNF soluble receptor into the plantar surface of the hindpaws enhanced the antinociceptive effect of acute morphine in rats. Subcutaneous inoculation of those vectors into hindpaws also delayed the development of chronic morphine tolerance in rats. TNF soluble receptor expressed by HSV vector reduced gene transcription of spinal TNFα and interleukin-1β (IL-1β) induced by repeated morphine. Furthermore, we found that TNF soluble receptor mediated by HSV reversed the upregulation of protein level of TNFα and IL-1β and phosphorylation of p38 mitogen-activated protein kinase induced by repeated morphine. These results support the concept that proinflammatory cytokines may have an important role in the pathogenesis induced by morphine. This study provides a novel approach to treating morphine tolerance.
authors: Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
authors: J
authors: J
authors: Sun
authors: S
authors: S
authors: Liu
authors: M
authors: M
authors: Mata
authors: D J
authors: DJ
authors: Fink
authors: S
authors: S
authors: Hao
references: J Neurosci. 2001 Oct 15;21(20):7881-8
references: 11588161
references: Trends Neurosci. 2005 Dec;28(12):661-9
references: 16246435
references: Brain Behav Immun. 2009 Feb;23(2):240-50
references: 18938237
references: Neuroscience. 2010 Aug 25;169(2):843-54
references: 20493931
references: Annu Rev Neurosci. 1996;19:265-87
references: 8833444
references: Eur J Pharmacol. 2006 Nov 21;550(1-3):91-4
references: 17026985
references: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13117-22
references: 20615975
references: Neurosci Res. 2001 Mar;39(3):281-6
references: 11248367
references: Eur J Neurosci. 2001 Oct;14(7):1091-104
references: 11683901
references: J Neuroimmunol. 1998 Mar 15;83(1-2):19-28
references: 9610669
references: J Neurovirol. 2003 Apr;9(2):165-72
references: 12707847
references: Gene Ther. 2007 Jul;14(13):1010-6
references: 17443214
references: Pain. 2008 Sep 15;138(3):587-597
references: 18374486
references: Am J Ther. 2010 Sep-Oct;17(5):498-510
references: 20844348
references: J Neurosci. 2008 May 28;28(22):5836-45
references: 18509045
references: Neuropsychopharmacology. 2011 Feb;36(3):664-76
references: 21068718
references: Nature. 2003 Aug 14;424(6950):778-83
references: 12917686
references: J Neurosci. 2005 Jan 12;25(2):409-16
references: 15647484
references: Neuroscience. 2001;103(4):1073-83
references: 11301214
references: J Neurochem. 1993 Nov;61(5):1766-73
references: 8228992
references: Neuropsychopharmacology. 2004 Feb;29(2):327-34
references: 14532913
references: Mol Neurobiol. 2009 Oct;40(2):101-7
references: 19468867
references: Brain Behav Immun. 2008 Nov;22(8):1178-89
references: 18599265
references: Hum Gene Ther. 2009 Jan;20(1):63-71
references: 20377371
references: Brain Res. 2006 Jan 19;1069(1):235-43
references: 16403466
references: J Neurosci. 2002 Sep 15;22(18):8312-23
references: 12223586
references: Nat Rev Mol Cell Biol. 2008 Feb;9(2):139-50
references: 18216770
references: J Neurosci. 2002 Nov 15;22(22):9980-9
references: 12427855
references: Gene Ther. 2008 Feb;15(3):183-90
references: 18033311
references: ScientificWorldJournal. 2007 Nov 02;7:98-111
references: 17982582
references: J Neurochem. 2003 Sep;86(6):1534-44
references: 12950462
references: J Clin Invest. 2007 Nov;117(11):3530-9
references: 17975673
references: Pain. 2001 May;92(1-2):5-9
references: 11323121
references: Mol Pain. 2006 Feb 17;2:6
references: 16503976
references: Drug Alcohol Depend. 2001 Apr 1;62(2):111-23
references: 11245967
references: FASEB J. 2009 Aug;23(8):2576-86
references: 19299480
references: Ann Neurol. 2006 May;59(5):843-51
references: 16634039
references: Pharmacol Rep. 2008 May-Jun;60(3):297-307
references: 18622054
references: Trends Neurosci. 2005 Feb;28(2):101-7
references: 15667933
references: Trends Pharmacol Sci. 2009 Nov;30(11):581-91
references: 19762094
references: Pain. 2005 May;115(1-2):50-9
references: 15836969
references: Gene Ther. 2001 Apr;8(7):551-6
references: 11319622
references: Neuroscience. 2010 Jan 20;165(2):569-83
references: 19833175
references: Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3211-6
references: 10077663
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: J Neurosci. 2004 Aug 18;24(33):7353-65
references: 15317861
references: Anesth Analg. 2011 Feb;112(2):454-9
references: 21081778
references: J Neurosci. 2010 Nov 17;30(46):15400-8
references: 21084596
references: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5856-61
references: 15809417
references: Brain Behav Immun. 2008 Jan;22(1):114-23
references: 17919885
references: J Pharmacol Exp Ther. 2005 Sep;314(3):1101-8
references: 15901793
references: Neuroscientist. 2004 Feb;10(1):40-52
references: 14987447