Antihyperalgesic effects of vanilloid-1 and bradykinin-1 receptor antagonists following spinal cord injury in rats

J Neurosurg Spine. 2007 May;6(5):420-4. doi: 10.3171/spi.2007.6.5.420.

Abstract

Object: The authors previously discovered that genes for the bradykinin-1 (B1) receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des-Arg9,Leu8]-bradykinin) antagonists on TH in animals following SCI.

Methods: The rats were subjected to contusion SCI and then divided into groups in which TH did or did not develop. The animals from both groups were given either AMG9810, Lys-(Des-Arg9,Leu8)-bradykinin, or the drug-specific vehicle (control groups). Animals were tested for TH preinjury and at regular intervals after SCI by using the hindlimb withdrawal latency test.

Conclusions: The administration of AMG9810 likely improves TH as a result of a generalized analgesic effect, whereas the effect of Lys-(Des-Arg9,Leu8)-bradykinin appears more specific to the reversal of TH. This information has potential usefulness in the development of treatment strategies for post-SCI neuropathic pain.

MeSH terms

  • Acrylamides / pharmacology*
  • Animals
  • Bradykinin Receptor Antagonists*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Kallidin / analogs & derivatives*
  • Kallidin / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / complications*
  • TRPV Cation Channels / antagonists & inhibitors*

Substances

  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acrylamides
  • Bradykinin Receptor Antagonists
  • Bridged Bicyclo Compounds, Heterocyclic
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Kallidin
  • kallidin, des-Arg(10)-