Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Intrathecal Protease-Activated Receptor Stimulation Produces Thermal Hyperalgesia through Spinal Cyclooxygenase Activity

Lee Koetzner, Joshua A. Gregory and Tony L. Yaksh
Journal of Pharmacology and Experimental Therapeutics October 2004, 311 (1) 356-363; DOI: https://doi.org/10.1124/jpet.104.069484
Lee Koetzner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua A. Gregory
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tony L. Yaksh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Activation of protease-activated receptors (PARs) in non-neural tissue results in prostaglandin production. Because PARs are found in the spinal cord and increased prostaglandin release in the spinal cord causes thermal hyperalgesia, we hypothesized that activation of these spinal PARs would stimulate prostaglandin production and cause a cyclooxygenase-dependent thermal hyperalgesia. PARs were activated using either thrombin or peptide agonists derived from the four PAR subtypes, delivered to the lumbar spinal cord. Dialysis experiments were conducted in conscious, unrestrained rats using loop microdialysis probes placed in the lumbar intrathecal space. Intrathecal thrombin stimulated release of prostaglandin E (PGE)2 but not aspartate or glutamate. Intrathecal delivery of the PAR 1-derived peptide SFLLRN-NH2 and the PAR 2-derived peptide SLIGRL both stimulated PGE2 release; PAR 3-derived TFRGAP and PAR 4-derived GYPGQV were inactive. Intrathecal thrombin had no effect upon formalin-induced flinching or tactile sensitivity but resulted in a thermal hyperalgesia. Intrathecal SFLLRN-NH2 and SLIGRL both produced thermal hyperalgesia. Consistent with their effects on spinal PGE2, hyperalgesia from these peptides was blocked by pretreatment with the cyclooxygenase inhibitor ibuprofen. SLIGRL-induced hyperalgesia was also blocked by the selective inhibitors SC 58,560 [5-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole; cyclooxygenase (COX) 1] and SC 58,125 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole; COX 2]. These data indicate that activation of spinal PAR 2 and possibly PAR 1 results in the stimulation of the spinal cyclooxygenase cascade and a prostaglandin-dependent thermal hyperalgesia.

Footnotes

  • This work was supported by National Institutes of Health Grant NS16541 to T.L.Y. L.K. was supported by Training Grant NS07407 to T.L.Y.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.104.069484.

  • ABBREVIATIONS: PAR, protease-activated receptor; COX, cyclooxygenase; SC 58,125, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole; SC 58,560, 5-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole; CNS, central nervous system; PGE, prostaglandin; MSP, myelencephalon-specific protease.

  • ↵1 Current address: Department of Neuropharmacology, Purdue Pharma L.P., Cranbury, NJ 08512.

    • Received April 5, 2004.
    • Accepted June 2, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 311 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 1
1 Oct 2004
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Intrathecal Protease-Activated Receptor Stimulation Produces Thermal Hyperalgesia through Spinal Cyclooxygenase Activity
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNEUROPHARMACOLOGY

Intrathecal Protease-Activated Receptor Stimulation Produces Thermal Hyperalgesia through Spinal Cyclooxygenase Activity

Lee Koetzner, Joshua A. Gregory and Tony L. Yaksh
Journal of Pharmacology and Experimental Therapeutics October 1, 2004, 311 (1) 356-363; DOI: https://doi.org/10.1124/jpet.104.069484

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleNEUROPHARMACOLOGY

Intrathecal Protease-Activated Receptor Stimulation Produces Thermal Hyperalgesia through Spinal Cyclooxygenase Activity

Lee Koetzner, Joshua A. Gregory and Tony L. Yaksh
Journal of Pharmacology and Experimental Therapeutics October 1, 2004, 311 (1) 356-363; DOI: https://doi.org/10.1124/jpet.104.069484
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • P-Glycoprotein Apical Efflux Ratio for Compound Optimization
  • Pharmacology of Carbamate Insecticides at Melatonin Receptors
  • Metalloporphyrins modify disease outcomes in parkinsonism
Show more Neuropharmacology

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics