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 journalArticlepeer-review

85 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

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