title: Effects of intrathecal ketorolac on human experimental pain.
abstract: BACKGROUND
  Nonsteroidal antiinflammatory drugs, the most commonly used analgesics, reduce pain not only by inhibiting cyclooxygenase at peripheral sites of inflammation but also by potentially inhibiting cyclooxygenase in the central nervous system, especially the spinal cord. Animal studies suggest that products of cyclooxygenase in the spinal cord do not alter pain responses to acute noxious stimuli but reduce pain and sensitization after peripheral inflammation. We used a spinal injection of small doses of the cyclooxygenase inhibitor ketorolac to survey the role of spinal cyclooxygenase in human experimental pain and hypersensitivity states.
  
  
  METHODS
  After regulatory agency approval and informed consent, we examined the effect of 2.0 mg intrathecal ketorolac in 41 healthy volunteers to acute noxious thermal stimuli in normal skin and to mechanical stimuli in skin sensitized by topical capsaicin or ultraviolet burn. We also examined the effect of intravenous ketorolac.
  
  
  RESULTS
  Intrathecal ketorolac reduced hypersensitivity when it was induced by a combination of ultraviolet burn plus intermittent heat and, according to one of the two analytical strategies, when it was induced by ultraviolet burn alone.
  
  
  CONCLUSIONS
  These data suggest a more limited role for spinal cord cyclooxygenase in human pain states than predicted by studies in animals.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. eisenach@wfubmc.edu
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
authors.forename: Regina
authors.initials: R
authors.lastname: Curry
authors.forename: Chuanyao
authors.initials: C
authors.lastname: Tong
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Houle
authors.forename: Tony L
authors.initials: TL
authors.lastname: Yaksh
mesh_terms: D000293:Adolescent; D000328:Adult; D002211:Capsaicin / Q000633:toxicity; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007278:Injections, Spinal; D020910:Ketorolac / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010812:Physical Stimulation / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects; D055815:Young Adult
chemical_list: D002211:Capsaicin; D020910:Ketorolac
references.citation: J Pharmacol Exp Ther. 1992 Oct;263(1):136-46
references.pmid: 1403779
references.citation: Anesthesiology. 1993 Aug;79(2):270-81
references.pmid: 8102041
references.citation: Pain. 2005 Feb;113(3):316-322
references.pmid: 15661439
references.citation: Am J Physiol. 1966 Oct;211(4):998-1004
references.pmid: 5951298
references.citation: Toxicol Sci. 2004 Aug;80(2):322-34
references.pmid: 15141096
references.citation: Anesthesiology. 2002 Oct;97(4):938-42
references.pmid: 12357162
references.citation: Presse Med. 1987 Sep 19;16(30):1465-8
references.pmid: 2957675
references.citation: Anesthesiology. 2006 Mar;104(3):403-10
references.pmid: 16508385
references.citation: Pain. 2007 Sep;131(1-2):70-82
references.pmid: 17257754
references.citation: Anesthesiology. 2002 Nov;97(5):1047-9
references.pmid: 12411784
references.citation: J Pain. 2001 Feb;2(1):25-35
references.pmid: 14622783
references.citation: Life Sci. 1994;54(11):715-20
references.pmid: 8107521
references.citation: Neuroreport. 1999 May 14;10(7):1511-6
references.pmid: 10380972
references.citation: J Neurosci. 2001 Aug 15;21(16):5847-53
references.pmid: 11487607
references.citation: Pain. 2003 Sep;105(1-2):65-70
references.pmid: 14499421
references.citation: Eur J Pain. 2007 Oct;11(7):756-63
references.pmid: 17234439
references.citation: J Neurosci. 2001 Nov 15;21(22):9001-8
references.pmid: 11698610
references.citation: Brain Res. 1999 Jan 23;816(2):512-7
references.pmid: 9878876
references.citation: Pain. 2000 Jan;84(1):57-64
references.pmid: 10601673
references.citation: Pain. 1995 Jun;61(3):391-399
references.pmid: 7478682
references.citation: Clin Pharmacol Ther. 2002 Aug;72(2):175-83
references.pmid: 12189364
references.citation: Anesth Analg. 2004 Jun;98(6):1536-1545
references.pmid: 15155302
references.citation: Anesthesiology. 2002 Jan;96(1):29-34
references.pmid: 11752998
references.citation: Pain. 1998 Jun;76(3):317-325
references.pmid: 9718250
references.citation: Neurosci Lett. 2003 Feb 27;338(2):99-102
references.pmid: 12566162
references.citation: Brain Res Rev. 2009 Apr;60(1):243-54
references.pmid: 19168094
references.citation: J Clin Anesth. 1993 Nov-Dec;5(6):459-62
references.pmid: 8123270
references.citation: Eur J Clin Pharmacol. 2000 Sep;56(6-7):459-62
references.pmid: 11049007
references.citation: Eur J Pain. 2009 May;13(5):524-32
references.pmid: 18691920
references.citation: Science. 1992 Aug 28;257(5074):1276-9
references.pmid: 1381521
references.citation: Anesth Analg. 2004 Jan;98(1):173-177
references.pmid: 14693614
references.citation: Pain. 2002 Oct;99(3):599-604
references.pmid: 12406536