Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Neurobiol Dis. 2014 Feb;62:394-406. doi: 10.1016/j.nbd.2013.10.020. Epub 2013 Oct 29.

Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy.

Author information

  • 1Division of Genetics & Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada; Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 2Division of Genetics & Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
  • 3Division of Genetics & Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada.
  • 4Division of Genetics & Development, Toronto Western Research Institute, and Spinal Program, Krembil Neuroscience Centre, University Health Network, Toronto, Ontario M5T 2S8, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada; Neuroscience Program, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Surgery, Division of Neurosurgery, University of Toronto, Toronto, Ontario M5T 2S8, Canada. Electronic address: Michael.Fehlings@uhn.on.ca.

Abstract

Cervical spondylotic myelopathy (CSM) is the commonest cause of spinal cord impairment worldwide and despite surgical treatment, it is commonly associated with chronic neuropathic pain and neurological impairment. Based on data suggesting a key role of sodium and glutamate mediated cellular injury in models of spinal cord compression, we examined whether riluzole, a sodium channel/glutamate blocker, could improve neurobehavioral outcomes in a rat model of CSM. To produce chronic progressive compression of the cervical spinal cord, we used an established model of graded mechanical cord compromise developed in our laboratory. The chronic (8weeks) mechanical compression of the cervical spinal cord resulted in persistent mechanical allodynia and thermal hyperalgesia at 8weeks. Moreover, we found increased expression of phosphorylated NR1 and NR2B in the dorsal horns as well as astrogliosis and increased microglia expression in the dorsal horns after mechanical compression. Following daily systemic administration for 7weeks after the induction of compression, riluzole (8mg/kg) significantly attenuated forelimb and hindlimb mechanical allodynia and alleviated thermal hyperalgesia in the tail. Importantly, riluzole led to a decrease in swing phase duration, an increase in hind leg swing speed and an increase paw intensity in gait analysis. Riluzole also decreased the number of phosphorylated NR1 and phosphorylated NR2B positive cells in the dorsal horns and the microglia activation in the dorsal horns. Together, our results indicate that systemic riluzole administration during chronic cervical spinal cord compression is effective at protecting spinal cord tissue, preserving neurobehavioral function and alleviating neuropathic pain, possibly by decreasing NMDA receptor phosphorylation in astrocytes and by eliminating microglia activation. As such, riluzole represents a promising clinical treatment for CSM.

© 2013.

KEYWORDS:

CSM; Cervical spondylotic myelopathy; Drug treatment; Neuropathic pain; Riluzole; Rodent model; Spinal cord; Spine

PMID:
24184328
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk