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

J Pain. 2006 Dec;7(12):884-91. doi: 10.1016/j.jpain.2006.04.009.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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


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