The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing.

Abstract

Intrathecal phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2), but not COX-1, inhibitors attenuate facilitated pain states generated by peripheral injury/inflammation and by direct activation of spinal glutamate and substance P receptors. These results are consistent with the constitutive expression of PLA2 and COX-2 in spinal cord, the spinal release of prostaglandins by persistent afferent input, and the effects of prostaglandins on spinal excitability. Whereas the acute actions of COX-2 inhibitors are clearly mediated by constitutively expressed spinal COX-2, studies of spinal COX-2 expression indicate that it is upregulated by neural input and circulating cytokines. Given the intrathecal potency of COX-2 inhibitors, the comparable efficacy of intrathecal versus systemic COX-2 inhibitors in hyperalgesic states not associated with inflammation, and the onset of antihyperalgesic activity prior to COX-2 upregulation, it is argued that a principal antihyperalgesic mechanism of COX-2 inhibitors lies with modulation of constitutive COX-2 present at the spinal level.

• Authors: Camilla I Svensson, Tony L Yaksh
• Journal: Annual review of pharmacology and toxicology (Annu Rev Pharmacol Toxicol) Vol. 42 Pg. 553-83 ( 2002) ISSN: 0362-1642 [Print] United States
• PMID: 11807183 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Prostaglandins
• Prostaglandin-Endoperoxide Synthases
• Phospholipases A
• Phospholipases A2

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Humans
• Hyperalgesia
• Pain (physiopathology)
• Phospholipases A (physiology)
• Phospholipases A2
• Prostaglandin-Endoperoxide Synthases (physiology)
• Prostaglandins (physiology)
• Signal Transduction
• Spinal Cord (drug effects, enzymology, physiology)
• Transcriptional Activation