Blocking EphA4 upregulation after spinal cord injury results in enhanced chronic pain
| Autor: | Lillian Cruz-Orengo, Anabel Puig, Aranza I. Torrado, Jorge D. Miranda, Scott R. Whittemore, Johnny D. Figueroa, Carmen Hernández, Cristina M. Ortiz, Annabell C. Segarra, Ixane Velázquez |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Time Factors Central nervous system Fluorescent Antibody Technique Pain Motor Activity Rats Sprague-Dawley Developmental Neuroscience Downregulation and upregulation Internal medicine Glial Fibrillary Acidic Protein medicine Animals RNA Messenger Spinal cord injury Spinal Cord Injuries Pain Measurement Reverse Transcriptase Polymerase Chain Reaction business.industry Receptor EphA4 Erythropoietin-producing hepatocellular (Eph) receptor Oligonucleotides Antisense medicine.disease Spinal cord Rats Up-Regulation medicine.anatomical_structure Allodynia Endocrinology Neurology Hyperalgesia Phosphopyruvate Hydratase Chronic Disease Neuropathic pain Female Neuron medicine.symptom business Neuroscience Psychomotor Performance |
| Zdroj: | Experimental Neurology. 202:421-433 |
| ISSN: | 0014-4886 |
| DOI: | 10.1016/j.expneurol.2006.07.005 |
| Popis: | Spinal cord injury (SCI) is characterized by a total or partial loss of motor and sensory functions due to the inability of neurons to regenerate. This lack of axonal regenerative response has been associated with the induction of inhibitory proteins for regeneration, such as the Eph receptor tyrosine kinases. One member of this family, the EphA4 receptor, coordinates appropriate corticospinal fibers projections during early development and is expressed in spinal commissural interneurons. Its mechanism of action is mediated by repulsive activity after ligand binding, but its role after trauma is unknown. We examined the temporal expression profile of this receptor after spinal cord contusion in adult rats by RT-PCR and immunohistochemistry. SCI induced a biphasic gene expression profile with an initial downregulation at 2 and 4 days post-injury (DPI) followed by a subsequent upregulation. Double labeling studies localized EphA4 immunoreactivity in neurons from the gray matter and astrocytes of the white matter. To test the role of this receptor, we reduced gene upregulation by intrathecal/subdural infusion of EphA4-antisense oligodeoxynucleotide (ODN) and subsequently assessed behavioral outcomes. No locomotor recovery was observed in the rats treated with the EphA4-antisense ODN. Interestingly, reducing EphA4 expression increased mechanical allodynia, as observed by the Von Frey test and decreased exploratory locomotor activity. These results indicate that upregulation of EphA4 receptor after trauma may prevent the development of abnormal pain syndromes and could potentially be exploited as a preventive analgesic mediator to chronic neuropathic pain. |
| Databáze: | OpenAIRE |
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