Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia

Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in...

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Bibliographic Details
Published in:The Journal of neuroscience 2004-03, Vol.24 (11), p.2727-2732
Main Authors: Ghilardi, Joseph R, Svensson, Camilla I, Rogers, Scott D, Yaksh, Tony L, Mantyh, Patrick W
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Brief Communications
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Disease Models, Animal
Hindlimb - injuries
Hindlimb - innervation
Hindlimb - physiopathology
Hyperalgesia - drug therapy
Hyperalgesia - enzymology
Hyperalgesia - physiopathology
Immunohistochemistry
Injections, Spinal
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Isoenzymes - pharmacology
Lumbosacral Region
Male
N-Methylaspartate - pharmacology
Neuroglia - enzymology
Neurons - drug effects
Neurons - enzymology
Neurons - physiology
Physical Stimulation
Prostaglandin-Endoperoxide Synthases - metabolism
Prostaglandin-Endoperoxide Synthases - pharmacology
Prostaglandins - metabolism
Proto-Oncogene Proteins c-fos - metabolism
Rats
Rats, Sprague-Dawley
Spinal Cord - drug effects
Spinal Cord - enzymology
Spinal Cord - physiopathology
Substance P - metabolism
Up-Regulation
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Summary:Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in physiologically significant levels after tissue injury, in the normal rat lumbar spinal cord, the majority of neurons and radial glia constitutively express high levels of COX-2 protein. Immediately after peripheral tissue injury and before any measurable upregulation of COX-2 protein in peripheral tissue or spinal cord, inhibition of constitutively expressed spinal COX-2 reduced injury-induced activation of primary afferent neurons, activation of spinal neurons, and the mechanical and thermal hyperalgesia that normally occurs after peripheral tissue injury. The present data demonstrate that constitutively expressed spinal COX-2 plays an important role in the initial hyperalgesia that follows peripheral tissue injury. These results suggest that blocking constitutive spinal COX-2 before tissue injury may reduce the initial peripheral and central sensitization that occurs after tissue injury.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5054-03.2004