title: Thrombospondin-4 contributes to spinal cord injury-induced changes in nociception.
abstract: BACKGROUND
  Our previous data have indicated that nerve injury-induced up-regulation of thrombospondin-4 (TSP4) proteins in dorsal spinal cord plays a causal role in neuropathic pain state development in a spinal nerve ligation model. To investigate whether TSP4 proteins also contribute to the development of centrally mediated changes in nociception after spinal cord injury (SCI), we investigated whether SCI induced TSP4 dysregulation, and if so, whether this change correlated with changes in nociception in a T9 spinal cord contusion injury model.
  
  
  METHODS
  Behavioural sensitivity to mechanical, thermal stimuli and locomotor function recovery were tested blindly in SCI or sham rats post-injury. Intrathecal antisense or mismatch control oligodeoxynucleotides were used to treat SCI rats with nociceptive hyperreflexia, and Western blots were used to measure TSP4 protein levels in dorsal spinal cord samples.
  
  
  RESULTS
  SCI induced below-level hindpaw hypersensitivity to stimuli. TSP4 protein levels are up-regulated in dorsal spinal cord of SCI rats with nociceptive hyperreflexia, but not in SCI rats without nociceptive hyperreflexia. There was no significant difference in motor function recovery post-injury between SCI rats with or without nociceptive hyperreflexia. Intrathecal treatment with TSP4 antisense, but not mismatch control, oligodeoxynucleotides led to reversal of injury-induced TSP4 up-regulation and nociceptive hyperreflexia in SCI rats.
  
  
  CONCLUSIONS
  SCI leads to TSP4 up-regulation in lumbar spinal cord that may play a critical role in mediating centrally mediated behavioural hypersensitivity. Blocking this pathway may be helpful in management of SCI-induced changes in nociception.
authors: Department of Anesthesiology & Perioperative Care, University of California Irvine, USA.
authors: J
authors: J
authors: Zeng
authors: D
authors: D
authors: Kim
authors: K-W
authors: KW
authors: Li
authors: K
authors: K
authors: Sharp
authors: O
authors: O
authors: Steward
authors: F
authors: F
authors: Zaucke
authors: Z D
authors: ZD
authors: Luo
mesh_terms: D000818:Animals; D005260:Female; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012021:Reflex, Abnormal; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D019699:Thrombospondins; C101864:thrombospondin 4
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