A retired Army colonel traveled to war-torn Ukraine with an unusual idea: inject botulinum toxin, the same substance used in Botox cosmetic treatments, directly around the painful nerve endings of amputees. The results suggest he was onto something.
In a study of 160 Ukrainian war amputees, those who received targeted botulinum toxin injections experienced a four-point drop in phantom limb pain after one month, compared to just a one-point reduction for patients receiving standard care alone. The findings, published in Archives of Physical Medicine and Rehabilitation, could eventually help millions of amputees worldwide who struggle with chronic pain in limbs that no longer exist.
“It’s a perplexing condition,” said Dr. Steven P. Cohen, a professor of anesthesiology at Northwestern University Feinberg School of Medicine and the study’s senior author. He’s also a retired U.S. Army colonel who served four overseas tours, and his son currently serves with the infantry.
“Botulinum toxin injected into painful stumps of residual limbs and around neuromas was on some outcome measures more effective than comprehensive medical and surgical treatment at one month post-treatment.”
A Novel Injection Technique
What made this approach different was where the injections went. Instead of injecting botulinum toxin into muscle or skin as is typical for cosmetic or pain procedures, the research team used ultrasound guidance to inject the substance directly around painful nerve endings called neuromas. These nerve clusters form at amputation sites and can trigger intense, burning pain in limbs that are no longer there.
The study took place between 2022 and 2024 at two hospitals in western Ukraine, where an estimated 100,000 soldiers and civilians have lost limbs since Russia’s full-scale invasion began. About one-fifth of participants received the botulinum toxin injections in addition to standard medical care, while the rest received comprehensive treatment that included surgical revision, nerve blocks, physical therapy, psychological support, and medications.
At the one-month mark, 69% of patients who received botulinum toxin achieved meaningful pain relief, defined as at least a 30% reduction. Only 43% of the comparison group reached that threshold. The injections appeared to work by quieting nerve activity and reducing local inflammation around the amputation sites.
Short-Term Relief, Long-Term Questions
But the story shifted at three months. Patients who received comprehensive care without botulinum toxin showed more lasting pain relief than those who got the injections. This aligns with previous research showing that botulinum toxin’s pain-relieving effects typically fade after about three months.
Dr. Roman Smolynets, an anesthesiologist at Multidisciplinary Clinical Hospital of Emergency and Intensive Care in Lviv, Ukraine, emphasized that the injections should complement, not replace, existing treatments.
“It could be another step toward helping amputees live with less pain and more dignity. But always as an additional point to comprehensive medical and surgical care, not as a monotherapy.”
Smolynets has treated thousands of war-injured patients at Ukraine’s largest trauma center. He and Cohen, who traveled to Ukraine in 2024 to help launch the study, have become close friends and collaborators. Smolynets visited Chicago in October for an observership program, spending time at Cohen’s pain medicine clinic and at the Shirley Ryan AbilityLab.
The research team believes their targeted “peri-neuromal” approach could help with other types of nerve pain, including shingles-related pain, carpal tunnel syndrome, and pain following surgeries like mastectomy. In the U.S., more than 2 million people live with limb loss, and most experience some form of post-amputation pain that limits their ability to use prosthetics and maintain quality of life.
Cohen and Smolynets are calling for larger randomized trials to confirm their findings and determine whether repeated botulinum toxin injections over time could produce sustained benefits, similar to how the treatment helps with chronic migraines. The two are also researching novel treatments for traumatic brain injury and PTSD in Ukraine, at Walter Reed, and Northwestern.
“As a retired colonel and the father of an infantry soldier who could be deployed in future conflicts and suffered from traumatic brain injury while at the U.S. Military Academy, this research carries special personal meaning for me,” Cohen said.
Archives of Physical Medicine and Rehabilitation: 10.1016/j.apmr.2025.09.026
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