title: The utility of ionotropic glutamate receptor antagonists in the treatment of nociception induced by epidural glutamate infusion in rats.
abstract: BACKGROUND
  The authors have previously demonstrated that human herniated disc material contains high concentrations of free glutamate. In an experimental model, elevated epidural glutamate concentrations in the lumbar spine can cause a focal hyperesthetic state.
  
  
  METHODS
  Rats underwent epidural glutamate infusion in the lumbar spine by a miniosmotic pump over a 72-hour period. Some rats underwent coinfusion with glutamate and ionotropic glutamate antagonists. Nociception was assessed by von Frey fibers and by assessment of glutamate receptor expression in the corresponding dorsal horn of the spinal cord.
  
  
  RESULTS
  The kainic acid antagonist, UBP 301, decreased epidural glutamate-based hyperesthesia in a dose dependent manner. Concordant with these findings, there was significant decrease in kainate receptor expression in the dorsal horn. The N-Methyl-4-isoxazoleproionic acid (NMDA) antagonist Norketamine also significantly diminished hyperesthesia and decreased receptor expression in the dorsal horn.
  
  
  CONCLUSIONS
  Both UBP 301, the kainic acid receptor antagonist and Norketamine, an NMDA receptor antagonist, dampened epidural glutamate-based nociception. Focal epidural injections of Kainate or NMDA receptor antagonists could be effective treatments for disc herniation-based lumbar radiculopathy.
authors.affiliation: Department of Neurosurgical Research, Roger Williams Medical Center, Rhode Island, USA.
authors.forename: Doreen B
authors.initials: DB
authors.lastname: Osgood
authors.forename: William F
authors.initials: WF
authors.lastname: Harrington
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Kenney
authors.forename: J Frederick
authors.initials: JF
authors.lastname: Harrington
keywords: Glutamate; UBP 301; nociception; norketamine
references.citation: Anesthesiology. 1998 Nov;89(5):1060-7
references.pmid: 9821993
references.citation: Anesth Analg. 2007 Oct;105(4):1152-9, table of contents
references.pmid: 17898404
references.citation: Spine (Phila Pa 1976). 2005 Mar 15;30(6):606-12
references.pmid: 15770173
references.citation: Neurosci Bull. 2009 Oct;25(5):319-23
references.pmid: 19784088
references.citation: Neuropharmacology. 2009 Jan;56(1):90-113
references.pmid: 18793656
references.citation: Eur J Pain. 2011 Feb;15(2):179-85
references.pmid: 20675160
references.citation: J Neurol Neurosurg Psychiatry. 1948 Feb;11(1):13-26
references.pmid: 18907039
references.citation: Arthritis Rheum. 1993 Sep;36(9):1214-22
references.pmid: 8216415
references.citation: Spine (Phila Pa 1976). 2006 Nov 15;31(24):2759-66
references.pmid: 17108825
references.citation: J Pharmacol Exp Ther. 2006 Oct;319(1):396-404
references.pmid: 16837561
references.citation: Pain. 2005 May;115(1-2):60-70
references.pmid: 15836970
references.citation: Spine (Phila Pa 1976). 1998 Apr 15;23(8):863-8; discussion 868-9
references.pmid: 9580952
references.citation: J Pain. 2006 Oct;7(10):768-77
references.pmid: 17018337
references.citation: Spine (Phila Pa 1976). 2000 Apr 15;25(8):929-36
references.pmid: 10767804
references.citation: Anesthesiology. 2009 May;110(5):1116-26
references.pmid: 19387178
references.citation: Mol Neurobiol. 2009 Dec;40(3):260-88
references.pmid: 19876771
references.citation: Neurosci Lett. 2007 Apr 12;416(2):123-7
references.pmid: 17314010
references.citation: J Pharmacol Exp Ther. 2002 Jan;300(1):149-56
references.pmid: 11752110
references.citation: Pain. 2008 Oct 31;139(3):569-577
references.pmid: 18692315
references.citation: Eur J Pharmacol. 2009 Nov 25;623(1-3):30-6
references.pmid: 19765585
references.citation: Spine (Phila Pa 1976). 2006 Aug 15;31(18):2053-8
references.pmid: 16915088
references.citation: Neurosci Lett. 2003 Nov 20;351(3):177-80
references.pmid: 14623135
references.citation: Spine J. 2010 Nov;10(11):999-1006
references.pmid: 20863766
references.citation: Clin J Pain. 2007 Mar-Apr;23(3):214-8
references.pmid: 17314579
references.citation: Eur J Pharmacol. 2004 Sep 19;499(1-2):155-61
references.pmid: 15363962
references.citation: Arch Biochem Biophys. 1992 Apr;294(1):115-22
references.pmid: 1550337
references.citation: J Orthop Res. 2001 Sep;19(5):881-6
references.pmid: 11562137
references.citation: Brain Res Rev. 2009 Apr;60(1):43-56
references.pmid: 19146876
references.citation: Pain. 2003 Nov;106(1-2):173-9
references.pmid: 14581125
references.citation: Pain. 2006 Jan;120(1-2):97-105
references.pmid: 16360275
references.citation: J Comp Neurol. 2002 Jan 21;442(4):365-77
references.pmid: 11793340