Cui Jian-Guo, University of Miami, Miami, USA

Agrin mechanisms in spinal cord injury induced neuropathic pain

Funded in: 2011, 2012

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Up to 85% of SCI patients may develop central neuropathic pain (SCINP), which can induce physical weakness, social functional hindrances, and pain-related emotional disturbances. Current pharmacological therapies including opioids, antidepressants, anticonvulsants, and NMDA antagonists are often ineffective over time.

Preliminary findings show that agrin, plays an important role in pain modulation. In experimental rat models, agrin was decreased only in the spinal cord of the rats that developed neuropathic pain. Moreover, increased agrin expression suppressed neuropathic pain. The underlying mechanism of action was the specific activation of inhibitory interneurons, which in turn induced pain suppression.
In this proposal, the following hypotheses will be tested:

  • spinal cord injury (SCI) results in neuronal agrin decrease and neuropathic pain in the spinal cord
  • agrin up-regulation suppresses SCINP
  • neuronal agrin activates interneurons to suppress pain

If the agrin research is successful, it will provide a new mechanism for spinal cord injury-induced neuropathic pain development and agrin delivery will offer a promising therapeutic approach. This will open a new door to improve the physical functions and social problems of these patients.