Targeted mutation of EphB1 receptor prevents development of neuropathic hyperalgesia and physical dependence on morphine in mice
<p>Abstract</p> <p>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...
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| Main Authors: | , , , , |
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| Format: | Book |
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SAGE Publishing,
2008-11-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | <p>Abstract</p> <p>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 (<it>EphB1+/+</it>) control littermate mice, but not in EphB1 receptor homozygous knockout (<it>EphB1-/-</it>) and heterozygous knockdown (<it>EphB1+/-</it>) 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 <it>EphB1+/+</it>, but not <it>EphB1-/- </it>and <it>EphB1+/- </it>mice. Cellularly, nerve injury-induced hyperexcitability of the medium-sized dorsal root ganglion neurons was prevented in <it>EphB1-/- </it>and <it>EphB1+/- </it>mice. In chronically morphine-treated mice, most of the behavioral signs and the overall score of naloxone-precipitated withdrawal were largely diminished in <it>EphB1-/- </it>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.</p> |
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| Item Description: | 10.1186/1744-8069-4-60 1744-8069 |