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

Joseph R. Ghilardi, Camilla I. Svensson, Scott D. Rogers, Tony L. Yaksh, Patrick W Mantyh

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2727-2732
Number of pages6
JournalJournal of Neuroscience
Volume24
Issue number11
DOIs
StatePublished - Mar 17 2004
Externally publishedYes

Fingerprint

Hyperalgesia
Cyclooxygenase 2
Wounds and Injuries
Spinal Cord
Central Nervous System Sensitization
Neurons
Afferent Neurons
Cyclooxygenase 2 Inhibitors
Pain Management
Neuroglia
Isoenzymes
Proteins
Up-Regulation

Keywords

  • Nociception
  • NSAID
  • Primary afferent
  • Prostaglandin
  • Rat
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia. / Ghilardi, Joseph R.; Svensson, Camilla I.; Rogers, Scott D.; Yaksh, Tony L.; Mantyh, Patrick W.

In: Journal of Neuroscience, Vol. 24, No. 11, 17.03.2004, p. 2727-2732.

Research output: Contribution to journalArticle

Ghilardi, Joseph R. ; Svensson, Camilla I. ; Rogers, Scott D. ; Yaksh, Tony L. ; Mantyh, Patrick W. / Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 11. pp. 2727-2732.
@article{cb580eb4b7ff465d851b5aa95d67efd2,
title = "Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia",
abstract = "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.",
keywords = "Nociception, NSAID, Primary afferent, Prostaglandin, Rat, Spinal cord",
author = "Ghilardi, {Joseph R.} and Svensson, {Camilla I.} and Rogers, {Scott D.} and Yaksh, {Tony L.} and Mantyh, {Patrick W}",
year = "2004",
month = "3",
day = "17",
doi = "10.1523/JNEUROSCI.5054-03.2004",
language = "English (US)",
volume = "24",
pages = "2727--2732",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "11",

}

TY - JOUR

T1 - Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia

AU - Ghilardi, Joseph R.

AU - Svensson, Camilla I.

AU - Rogers, Scott D.

AU - Yaksh, Tony L.

AU - Mantyh, Patrick W

PY - 2004/3/17

Y1 - 2004/3/17

N2 - 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.

AB - 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.

KW - Nociception

KW - NSAID

KW - Primary afferent

KW - Prostaglandin

KW - Rat

KW - Spinal cord

UR - http://www.scopus.com/inward/record.url?scp=1642293993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642293993&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.5054-03.2004

DO - 10.1523/JNEUROSCI.5054-03.2004

M3 - Article

C2 - 15028765

AN - SCOPUS:1642293993

VL - 24

SP - 2727

EP - 2732

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 11

ER -