A large part of selecting and implementing successful post-amputation pain management involves understanding from where the pain originates, but pinpointing where in the body acute and chronic pain originates from poses challenges.
Emily Petrus, PhD, assistant professor of Anatomy, Physiology and Genetics at the Uniformed Services University’s (USU) F. Edward Hébert School of Medicine, is studying how the brain adapts after injury. The study explores the mechanisms involved with pain following a loss of nerve supply (denervation) and amputation.
“If we understand how some people just don’t have pain, we could try to figure out how to get that to happen for everybody,” Petrus said.
Petrus’ research aims to understand why some amputation patients experience beneficial recovery while others experience pain conditions. Part of understanding pain processes involves looking at the brain after an amputation. Brain plasticity, or the process by which the brain adapts after injury, occurs after most amputation events. For example, after the loss of a hand, areas of the brain responding to sensory input from the missing hand are recruited to respond to the intact hand instead.
By identifying the neural “drivers of plasticity,” Petrus said, the research team attempts to find what “particular groups of cells might underlie the adaptations that motivate the brain to change.”
Since there is no set pathway the brain follows in restructuring after injury, there is no way to predict how the brain will respond to amputation.
“When we look at the functional activity of the brain with fMRI [functional magnetic resonance imaging],” said Petrus, “people who have phantom limb pain and people who don’t have fairly similar brain activity patterns.” Because there are no clear indicators for how the patient will recover, there is also no broadly beneficial intervention to provide care once an issue arises.
For some patients, rerouting of the brain’s functions results in enhanced sensory input from other areas.
“For example, a person who lost an arm might learn to paint with their feet. So that’s not learning to use a prosthetic, but that’s a recovery in a different way to adapt to the injury,” Petrus said.
For others, the rerouting of the brain can result in hypersensitivity, referred pain, or phantom limb pain.
Petrus examines brain responses using mouse model whisker nerve bundles. For a mouse, whiskers aid in daily sensory activities equivalent to a person’s hands. Additionally, the mouse’s brain region devoted to whiskers is large. This larger area assists the team in locating the region during fMRI scans, electrophysiological measurements, which measure the electrical activity of neurons, and histology studies, staining and sectioning tissue for examination beneath a microscope.
Petrus said the research examines the brain to “characterize at the gene expression level, at the synaptic level, the neuron level, the circuit level, and the behavior level,” what changes occur, which may explain the differences between populations who respond well to amputations and those who do not.
“If there was some kind of marker we could use—to either predict how people react or try to characterize what is underlining the good or the bad adaptation—we could modulate those adaptations to enhance beneficial recovery, or to reduce maladaptive problems,” said Petrus.
While this model does not enable categorization of either referred or phantom limb pain, it does allow understanding of the brain’s response in a different way. Petrus and her team also characterize the activity of brain cells following amputation.
“This activity is what yields the fMRI signal observed in both humans and mice. The goal is to locate the mechanisms that the neurons in the brain use to adapt to injury. In a human, when you study their response to injury, you don’t have the mechanism, you just can look at what the brain is doing, what the person is doing. But when you are using a mouse model, you can get all the way down to genes, receptors, and synapses. So you can really understand the mechanism,” Petrus said.
According to Petrus, once the mechanism is found, there is potential for treatments that approach pain management or recruit beneficial adaptations at the source. The theory is, after locating the specific cells or mechanisms that underlie these adaptations, they could be modulated, or changed, to enhance recovery.
“For example, if you put a magnet [on that area of the brain] and you pulse current through the magnet, it will turn on or off different parts of the brain,” Petrus said. By modulating the brain’s response, you may be “turning that brain region off, [and] maybe that pain perception could go away.”
Petrus’ goal is to one day utilize the results of her research to help people with limb loss through their rehabilitation and recovery. She is now in collaboration with Tawnee Sparling, MD, an assistant professor in the department of Physical Medicine and Rehabilitation at USU. Petrus and Sparling are working on a review that bridges the gap between clinical observation and intervention and findings from animal models of amputation.
Editor’s note: This story was adapted from materials provided by the Defense Visual Information Distribution Service.
