Defining a spine-to-brain pathway that drives pain

2021

Challenge

Painful stimuli evoke a mixture of sensations, negative emotions, and behaviors. These myriad effects are thought to be produced by the combined activity of certain neural pathways that ascend from the spinal cord to the brain. Identifying these pathways in the brain represents a key step toward understanding and treating chronic pain.

Advance

In a new study, IRP investigators led by Alexander Chesler, Ph.D., used genetics, imaging, and behavioral studies to uncover a pathway from the spinal cord to the brain involved in ongoing pain. They showed that activating a specific subset of spinal neurons evokes a full repertoire of pain-related behaviors in mice. This occurs even when the animals were not exposed to any external provocations that would cause them pain or irritation. Moreover, the researchers discovered that these spinal cord neurons send signals to a tiny cluster of neurons in a part of the brainstem called the parabrachial nucleus. Finally, they demonstrated that those brainstem neurons are required for the animals to sense and respond to pain and that they are activated by harmful stimuli sustained over longer periods of time but not by aversive events that last only a short time.

Impact

The study revealed a set of cells in the spinal cord and brainstem that are necessary for normal pain sensation. What’s more, because those neurons can be distinguished from other cells by the presence of a specific molecule called Substance P and a specific receptor on the cells called Tacr1, scientists may be able to develop interventions that specifically target those neurons in order to alleviate both acute and chronic pain.

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