One afternoon in May 2011, Doug Pike was riding his motorcycle near his home in Virginia when a car coming from the other direction crossed the median line and hit him. Pike landed on the car's windshield, and his leg got caught in the handlebars of his motorcycle. A nurse who happened to live in the neighborhood raced to help before an ambulance took him to a trauma center. Pike was in intensive care for weeks and underwent more than two dozen surgeries, including one to insert screws to fix a broken fibula and tibia, multiple bone and skin grafts, and two knee replacements.
His medical crisis culminated in an amputation in 2023 after he was faced with a life-threatening infection. Pike thought the amputation would finally end the agony he had endured for the past 12 years, but about four days after the surgery, he was jolted by the most excruciating pain he'd ever felt. It emanated from his left leg—the one that was no longer there. “It was a harsh sensation,” recalls Pike, 58, a retired audio engineer for the music industry who now lives in Anderson, IN. “I could feel pins and needles up and down the bottom of my foot. Then the sensation went up my leg. After a couple of hours, I felt like I was being electrocuted or hooked up to a car battery.”
Pike was experiencing a phenomenon called phantom limb pain, which can happen following amputation. In some cases, the pain is unbearable. Other times, the sensations are more unsettling than painful. “You wake up in the middle of the night, and you reach for your leg and it isn't there,” Pike says.
Phantom limb pain is thought to affect the majority of people who undergo amputation, says Hunter Schone, PhD, a neuroscientist at the Rehab Neural Engineering Labs at the University of Pittsburgh, who has studied the phenomenon. Sometimes the pain occurs just after surgery. Other times, it can persist for years. “Patients will say that the pain is coming from a body part that is no longer there,” says Dr. Schone. “The challenge for clinicians is treating something they can't point to and ask, ‘It hurts exactly here?’”
The pain is variously described as sharp, shooting, throbbing, stabbing, burning, aching, cramping, or even like lying in a nest of crawling insects, according to a 2022 review in the Journal of Neurology, Neurosurgery, and Psychiatry. It was previously dismissed as a psychological problem or delusional perception, but within the last couple of decades it has been recognized as a valid pain condition, says Dr. Schone, who co-authored the review.
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In this episode of the Brain & Life podcast, Dr. Katy Peters is joined by Staff Sergeant John Kriesel as he shares his experience of losing his legs in combat. He discusses his recovery process, phantom limb pain, and what changes he hopes to see in treatment options for others.
The mechanisms underlying phantom limb pain involve the brain and the peripheral nervous system, the network of nerves throughout the body that carries signals to and from the brain and spinal cord. When a limb is amputated, the nerves that once allowed an arm or leg to move and feel sensations are “suddenly cut off from their muscle-end targets,” says Dr. Schone. “These cut nerves start to send random, disorganized neural signals upstream, back to the spinal cord and the brain.”
It's not clear which neural pathways are affected by these random signals and how, exactly, they go seemingly haywire, says Dr. Schone, who believes research needs to focus on how these peripheral factors contribute to phantom limb pain. Understanding more about these neural pathways and signals may influence how amputation surgeries are performed and what is done with residual nerves following amputation. Researchers aim to learn more about the molecular changes triggered by the amputation that lead to phantom pain, he says.
Dozens of treatments, including various prescription and nonprescription drugs, nerve blocks, neuromodulation, and cognitive behavioral therapy, have been used to ease phantom pain, with varying levels of success.
A behavioral treatment called mirror therapy involves positioning an amputee's intact limb in front of a mirror and the missing limb behind the mirror, creating a visual illusion of two limbs. When the patient moves the existing limb, the brain “sees” the missing limb moving in the mirror, allowing the patient to experience the imaginary movement of the amputated limb as normal movement because of the mirror. The therapy may trick the brain into thinking the missing limb is still there and, in turn, possibly reduce the phantom limb pain. But Dr. Schone says no “strong, well-controlled evidence” supports its effectiveness.
What's needed, Dr. Schone says, are rigorous clinical studies with more patients and more control therapies, and a better understanding of the basic science behind peripheral contributors of pain. For now, some research is focused on how to reduce the risk by improving amputation surgery. “Phantom limb pain is horrible,” says Paul Cederna, MD, chief of plastic surgery at the University of Michigan in Ann Arbor. “It wakes people up at night and negatively affects their quality of life in a dramatic way. They rely on a lot of medications to try to reduce the pain.” Dr. Cederna and other surgeons are exploring newer amputation techniques.
One such technique, called regenerative peripheral nerve interface, involves rerouting severed nerve fibers into muscle grafts. Typically, divided nerve ends keep sprouting nerve fibers in an attempt to reconnect with their original targets. If no target is found, a ball of raw nerve endings, known as a neuroma, forms, which can cause severe pain locally and in the phantom limb. When a muscle graft is placed on the end of the nerve, the nerve restimulates the muscle graft, which prevents the formation of a neuroma.
Electrodes are then implanted in the muscle graft of what is left of the limb following amputation to boost nerve signals that can then be directed to control an artificial limb, Dr. Cederna says. Early indications from patients suggest that the approach can reduce the risk of neuroma pain and phantom pain and improve prosthetic function, he says.
Some evidence suggests that the more advanced prostheses, which provide both movement and sensory feedback, may reduce the chances of phantom pain, says Gregory Clark, PhD, a neuroengineer at the University of Utah, who focuses on fine-tuning the use of hundreds of implanted electrodes near muscle fibers. The result is a prosthesis that moves more naturally and feels more real than previous versions.
This spring Doug Pike was fitted with an artificial limb and is walking again with more ease. His phantom pain, which at one point reached a 10 out of 10 on his personal pain scale, has gradually faded. “It was short-lived but harsh,” he says. “I don't feel sorry for myself. Sometimes you can't control what happens in your life, but you can control your response.”
How Prostheses May Ease Phantom Limb Pain
Prostheses that provide both movement and sensory feedback and that the brain senses as part of the body could help reduce the risk of phantom limb pain, says Gregory Clark, PhD, professor of biomedical engineering and director of the Center for Neural Interfaces at the University of Utah in Salt Lake City. “We speculate that when the prosthesis starts to feel like a wearer's real limb, the brain is tricked into thinking it is real,” he says. “The phantom limb doesn't have a place to live in the brain anymore. So it goes away. And as the phantom limb fades away, so does the pain.”
One such prosthesis Dr. Clark is involved with—an artificial arm invented and manufactured by DEKA—works by sending and receiving signals to and from several hundred electrodes implanted near motor and sensory nerve and muscle fibers. Nerves are like hotlines that send signals back and forth between the brain and the rest of the body, says Dr. Clark. The electrodes record electrical activity representing motor commands, which are then translated into physical movement of the arm. The electrodes also receive output from sensors on the artificial arm and stimulate associated sensory nerve fibers, which send feedback to the brain. Wearers can discern whether a surface is smooth or rough, large or small. “People can move the bionic arm naturally and intuitively,” says Dr. Clark. “It's so lifelike that wearers start thinking of the prostheses as parts of their bodies.”
The prosthesis has been tested in the lab and in supervised real-world settings, and Dr. Clark hopes to start clinical trials and eventually make it available to all patients.
If artificial limbs have a sense of touch, the emotional component becomes as important as the practical one. “The ability to connect physically is key,” says Dustin Tyler, PhD, professor of biomedical engineering and founder and director of the Human Fusions Institute at Case Western Reserve University in Cleveland. “When you touch someone's hand, you get a physical and emotional connection” which can be rewarding, says Dr. Tyler, who develops the brain-computer interfaces that control the prostheses.
Some of the same technologies being used to help people with spinal cord injuries regain mobility are being applied to artificial limbs. “We are building algorithms that translate brain activity into movement or, in the inverse, translate sensory input into a set of electrical impulses that stimulate the brain” to recognize what is being felt, says Nicholas Hatsopoulos, PhD, professor of neuroscience at the University of Chicago.
The goal is to have a seamless bidirectional brain-computer interface between the motor output and sensory input. Dr. Hatsopoulos hopes to test the approaches on people who have lost limbs. “Ultimately, these bidirectional interfaces will enable amputees to feel that their artificial limbs are part of their own bodies,” he says.
