TrkA and PKC-epsilon in thermal burn-induced mechanical hyperalgesia in the rat.

Abstract

UNLABELLED:

Although mechanical hyperalgesia associated with medical procedures is the major source of severe pain in burn-injured patients, little is known about its underlying mechanism. One reason for this has been the lack of a model for mechanical hyperalgesia at the site of injury. We have modified an established partial-thickness burn model in the rat to produce long-lasting primary mechanical hyperalgesia, which is present from the first measurement at 0.5 h, reaches a maximum at 3 days, and is still significant after 7 days. Because nerve growth factor (NGF), which is elevated in burn-injured tissue, produces mechanical hyperalgesia and activates protein kinase C (PKC)-epsilon, a key mediator in inflammatory and neuropathic pain, we used this model to evaluate the role of the NGF receptor, tyrosine-receptor kinase A (TrkA), and PKC-epsilon in burn-induced primary mechanical hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides to TrkA and PKC-epsilon, starting 3 days before inducing a burn injury, caused dose-related decrease of burn-induced primary mechanical hyperalgesia. In addition, intradermal injection of a PKC-epsilon-selective inhibitor eliminated hyperalgesia. Our model provides a method to elucidate the underlying mechanism of burn-injury pain as well as to screen for targets for novel analgesic treatments of this important clinical condition.

PERSPECTIVE:

This manuscript presents the first model of thermal injury-induced mechanical hyperalgesia which mimics prolonged duration of clinical burn injury pain. We also perform proof of concept experiments demonstrating that our model provides a method to elucidate the mechanism of this important clinical condition.

• Authors: Gretchen J Summer, Kathleen A Puntillo, Christine Miaskowski, Olayinka A Dina, Paul G Green, Jon D Levine
• Journal: The journal of pain (J Pain) Vol. 7 Issue 12 Pg. 884-91 (Dec 2006) ISSN: 1526-5900 [Print] United States
• PMID: 17157774 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Enzyme Inhibitors
• Oligodeoxyribonucleotides, Antisense
• Peptides
• protein kinase inhibitor peptide
• Receptor, trkA
• Protein Kinase C-epsilon

Topics

• Animals
• Burns (complications)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage)
• Hyperalgesia (drug therapy, etiology, metabolism)
• Male
• Oligodeoxyribonucleotides, Antisense (administration & dosage)
• Pain Measurement (methods)
• Pain Threshold (drug effects, physiology)
• Peptides (administration & dosage)
• Protein Kinase C-epsilon (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (physiology)
• Receptor, trkA (genetics, metabolism)
• Time Factors