CHICAGO — Most war amputees experience steady improvements in pain, psychological symptoms and quality of life over time, according to a new study that followed 156 Ukrainian amputees for one year and was led by Northwestern Medicine and collaborators in Ukraine.
The findings will be published on Tuesday (April 21) in the journal eClinicalMedicine, part of The Lancet Group.
The study is the first to track over time how anxiety, depression and quality of life interact with pain in an amputee population. It also sought to answer a long-standing question in chronic pain medicine: Does pain drives emotional distress, or does distress drive pain?
The answer, in this case, depended on the type of post-amputation pain, which can present as either phantom limb pain (pain that feels like it comes from the missing limb) or residual limb pain (pain in the remaining stump).
For phantom pain, psychological distress tended to come first. Specifically, amputees who had higher levels of depression or poorer quality of life (poor social support, poor function and poor sleep) shortly after their injury were more likely to report persistent phantom pain months later.
For residual limb pain, the pattern was different. Participants with more severe residual pain at baseline were more likely to develop depression over time. That could be because stump pain often prevents amputees from using their prosthetics, thus severely limiting their mobility.
Post-amputation pain affects most amputees . In the U.S., more than 2 million people live with limb loss. In Ukraine, it is estimated that over 100,000 soldiers and civilians have lost limbs since Russia's full-scale invasion, which began in 2022.
According to the authors, this study supports a new two-staged understanding of post-amputation recovery. Early improvements in pain are driven largely by healing over time and medical care. But later, lingering post-amputation pain appears to be more strongly linked with psychological health and quality of life.
"Thus, people with persistent post-amputation pain need to be continually screened for psychologic distress," said study senior author Dr. Steven P. Cohen , a professor of anesthesiology and the vice chair of research and pain medicine at Northwestern University Feinberg School of Medicine.
Cohen also noted that overall, the findings are encouraging and can help with counseling and setting expectations. "People are likely to improve and recover, so they may be less likely to worry and become depressed and anxious," Cohen said. "Still, worse post-amputation pain, particularly for residual limb pain, can lead people to be depressed, creating a vicious circle."
Cohen, who traveled to Ukraine in 2024 to help launch the study, is a retired U.S. Army colonel who served four overseas tours in support of military operations; his son currently serves in the U.S. Army.
A year of recovery
The study followed 156 Ukrainians, with blast-related injuries and predominantly single lower-limb amputations. Most participants were in their mid-30s and had served in the war. They entered the study a median of 3.7 months after amputation and were followed for one year, with evaluations at baseline, three, six and 12 months.
At each time point, scientists measured pain on a 0 – 10 scale, anxiety and depression using validated clinical scales and overall quality of life on a 0 – 100 scale.
Over 12 months, median outcomes improved substantially across all measures:
- Phantom limb pain dropped from 4.3 to 1.1
- Residual limb pain dropped from 3.8 to 0.4
- Anxiety scores fell by more than half
- Depression declined steadily
- Quality of life improved from 57.8 to 77.2
The research team used statistical models to determine how pain and psychological factors were related and how they influenced one another over time.
The participants all received standard of care within a large medical system in western Ukraine during the study period. That included physical rehab, psychological therapies and medications, such as antidepressants and nerve-targeting drugs, but not opioids. Some patients also underwent additional procedures, such as nerve-targeted interventions or surgery.
Next steps
Cohen noted that the findings come from a unique population who were generally previously healthy (a requirement for joining the military) prior to serving in the war and suffered intense physical and psychological trauma.
He said future research will need to examine how pain and emotional distress interact over time in other civilian groups with trauma and chronic pain. He also said that more research is needed to test whether targeted and alternative treatments for psychological distress, such as psychotherapy, biofeedback or ketamine infusions — can improve pain outcomes.
The other Northwestern co-author is Dr. Joana Barroso . First author Dr. Roman Smolynets, a collaborator of Cohens on multiple studies in conjunction with the U.S. Department of Defense, led this study from Danylo Halytsky National Medical University in Lviv, Ukraine.
The study is titled, "The Association Between Quality of Life, Anxiety and Depression, and Residual Limb and Phantom Limb Pain in War-Related Amputees: A Year-Long Observational Study." It was partially funded by the U.S. Department of Defense (via the Department of Physical Medicine & Rehabilitation at Uniformed Services University).
