A brainstem-spinal circuit controlling movement in response to pain

2018

Challenge

Response to danger needs to be rapid and appropriate. In humans, movements that remove the body from a source of pain often precede conscious pain perception. Much is known about local spinal cord circuits for simple reflexive responses, but the mechanisms underlying more complex behaviors remain poorly understood.

Advance

IRP researchers, led by Alexander Chesler, Ph.D., described a brainstem circuit that controls motor responses to certain painful or uncomfortable stimuli. The team’s experiments characterized a highly interconnected excitatory circuit involving the dorsal spinal cord, parabrachial nucleus (PBNl), and reticular formation (MdD). A combination of chemogenetic, optogenetic, and genetic ablation approaches revealed that PBNl neurons that release a neuropeptide chemical called Substance P are activated by painful stimuli and trigger robust escape responses to heat through connections to the MdD. Remarkably, the neurons in the MdD also express Substance P and target both the spinal cord and PBN, creating a feed-forward excitatory neural circuit that serves to heighten pain responses.

Impact

These findings identify a neurological pathway that controls appropriate behavioral responses to painful stimuli. Deeper knowledge of how this spinal-brainstem neural circuit works will provide a better understanding of the changes that occur in the brain in patients with chronic pain.

Publications

Barik A, Thompson J, Seltzer M, Ghitani N, Chesler A. (2018). A Brainstem-Spinal Circuit Controlling Nocifensive Behavior. Neuron. 100(6):1491-1503.