HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Targeted mutation of EphB1 receptor prevents development of neuropathic hyperalgesia and physical dependence on morphine in mice.

Abstract
EphB receptor tyrosine kinases, which play important roles in synaptic connection and plasticity during development and in matured nervous system, have recently been implicated in processing of pain after nerve injury and morphine dependence. Subtypes of the EphB receptors that may contribute to the neuropathic pain and morphine dependence have not been identified. Here we demonstrate that the subtype EphB1 receptor is necessary for development of neuropathic pain and physical dependence on morphine. The results showed that peripheral nerve injury produced thermal hyperalgesia in wild-type (EphB1+/+) control littermate mice, but not in EphB1 receptor homozygous knockout (EphB1-/-) and heterozygous knockdown (EphB1+/-) mice. Hyperalgesia in the wild-type mice was inhibited by intrathecal administration of an EphB receptor blocking reagent EphB2-Fc (2 microg). Intrathecal administration of an EphB receptor activator ephrinB1-Fc (1 microg) evoked thermal hyperalgesia in EphB1+/+, but not EphB1-/- and EphB1+/- mice. Cellularly, nerve injury-induced hyperexcitability of the medium-sized dorsal root ganglion neurons was prevented in EphB1-/- and EphB1+/- mice. In chronically morphine-treated mice, most of the behavioral signs and the overall score of naloxone-precipitated withdrawal were largely diminished in EphB1-/- mice compared to those in the wild-type. These findings indicate that the EphB1 receptor is necessary for development of neuropathic pain and physical dependence on morphine and suggest that the EphB1 receptor is a potential target for preventing, minimizing, or reversing the development of neuropathic pain and opiate dependence.
AuthorsYuan Han, Xue-Song Song, Wen-Tao Liu, Mark Henkemeyer, Xue-Jun Song
JournalMolecular pain (Mol Pain) Vol. 4 Pg. 60 ( 2008) ISSN: 1744-8069 [Electronic] England
PMID19025592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Morphine
  • Receptor, EphB1
Topics
  • Animals
  • Ganglia, Spinal (pathology)
  • Hyperalgesia (etiology, prevention & control)
  • Mice
  • Mice, Knockout
  • Morphine (pharmacology)
  • Mutagenesis, Site-Directed
  • Receptor, EphB1 (genetics, physiology)
  • Substance-Related Disorders (etiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: