The role of VGLUT1 expressing proprioceptive afferents on exercise-induced pain and motor recovery following peripheral nerve injuries

Funding Details
Canadian Institutes of Health Research
  • Grant type: CIHR Fellowship
  • Year: 2019/20
  • Total Funding: $21,667
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Project Summary

Neuropathic pain is a debilitating chronic pain condition, caused by injuries to the nervous system and impacts 7 to 8% of the global population. Individual differences in pain tolerance, and the diverse cause of nerve injuries including trauma, sport injuries, inflammation, and chemotherapy, makes neuropathic pain particularly difficult to treat. My proposal aims to investigate new therapeutic targets. It is known that exercise benefits both pain and motor recovery after injuries, but a key question is how exercise changes the activity of the nervous system, and contributes to relief of pain and motor disability. To address this gap, I will empirically quantify the effects of exercise on pain and motor functions in a rodent model of peripheral nerve injury. Rodents will exercise voluntarily on a running wheel placed inside their cages, I will examine the cellular and molecular changes in the spinal cord - a key hub of sensory and motor processing. Next, I will then target these changes, and test their ability on reducing pain and motor disabilities. Specifically, peripheral nerve injuries cause a loss of VGLUT1 (vesicular glutamate transporter 1) expressing neurons in the spinal circuit, I will investigate whether the pain and motor disability are linked to a reduction in VGLUT1, and whether exercise can rescue this loss. Finally, I will manipulate the activity of VGLUT1 using pharmacological approaches, and test whether this can improve pain and motor disability following peripheral nerve injuries. Elucidating these mechanisms will help realise an evidence-based therapeutic solution for neuropathic pain and motor recovery, aid translational implementation of rehabilitation based treatments, and relieve the huge economic burden on the health care system.