Following up
Triggering movement
Story by Tara Narwani
Immediately after a spinal cord injury, people undergo what is called spinal shock. Not only is communication between brain and muscle impaired, but also the muscles themselves are flaccid—they cannot be stimulated to contract. However, even if the spinal cord is completely severed, muscles below the injury site regain tone over time and may begin to spasm or exhibit spasticity. In the case of animals with a complete spinal cord injury, this regained muscle activity can even allow the recovery of walking on a treadmill.
Dr. Dave Bennett and Dr. Karim Fouad have been interested, respectively, in how spasticity and the recovery of locomotion take place after spinal cord injury. They’ve recently made an unexpected discovery. “We came together and found that the same mechanism is actually contributing to spasticity but also to the recovery of motor function,” explains Dr. Fouad.
For muscles to respond to stimuli, the nerve cells that run to them, which are called motoneurons, must be excitable. It’s known that the brain chemical serotonin is essential for making the motoneurons excitable. Serotonin travels from the brain along the spinal cord to each motoneuron, where it attaches to a receptor on the cell and triggers the appropriate biochemical changes.
The big question was, if the flow of serotonin is blocked due to a spinal cord injury, how do motoneurons regain their excitability? The researchers did a series of experiments testing the effect of various drugs on the behaviour of the motoneurons. “With each drug, we could see whether the excitation was gone or not,” say Dr. Fouad.
In the end, the results showed that a particular type of serotonin receptor changed after spinal cord injury from one that requires serotonin to one that’s active without it. In essence, the body compensates for an effect of the injury.
Together with another researcher, Dr. Monica Gorassini, Drs. Fouad and Bennett also demonstrated that the same drug that reduced motoneuron excitability in the lab could reverse the recovery of an animal that was successfully trained to walk on a treadmill, as well as reduce muscle spasms in human patients.
The experimental conclusions have implications for the future treatment of spinal cord injury. The concern is that, by administering a drug that increases the excitability of motoneurons to promote recovery, spasticity would be triggered simultaneously.
According to Dr. Fouad, the ideal would be to find “drugs that work to reduce the sensory input that triggers spasms but that can also crank up excitability.” But, that will have to wait for future work.