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

Yuan Han, Xue Song Song, Wen Tao Liu, Mark Henkemeyer, Xue Jun Song

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 μg). Intrathecal administration of an EphB receptor activator ephrinB1-Fc (1 μg) 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.

Original languageEnglish (US)
Article number60
JournalMolecular Pain
Volume4
DOIs
StatePublished - Nov 21 2008

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EphB1 Receptor
Morphine Dependence
Hyperalgesia
Eph Family Receptors
Neuralgia
Mutation
Opioid-Related Disorders
Peripheral Nerve Injuries
Neuronal Plasticity
Wounds and Injuries
Spinal Ganglia
Naloxone
Protein-Tyrosine Kinases
Morphine
Nervous System

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

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Targeted mutation of EphB1 receptor prevents development of neuropathic hyperalgesia and physical dependence on morphine in mice. / Han, Yuan; Song, Xue Song; Liu, Wen Tao; Henkemeyer, Mark; Song, Xue Jun.

In: Molecular Pain, Vol. 4, 60, 21.11.2008.

Research output: Contribution to journalArticle

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