A retired army colonel traveled to war-torn Ukraine with an unusual idea: inject botulinum toxin, the same substance used in Botox cosmetic treatments, right around the painful nerve endings of amputees. The results show he was on to 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 only a one-point drop for patients receiving only standard care. The findings, published in the Archives of Physical Medicine and Rehabilitation, could ultimately help millions of amputees around the world who struggle with chronic pain in limbs that no longer exist.
“It’s a complicated situation,” said Dr. Steven P. Cohen, professor of anesthesiology at Northwestern University Feinberg School of Medicine and senior author of the study. He is also a retired US Army colonel who served four tours overseas and his son is currently serving in the infantry.
“Botulinum toxin injected into painful residual limb stumps and around neuromas was on some outcome measures more effective than comprehensive medical and surgical therapy one month after treatment.”
A new injection technique
What made this approach different was where the injections went. Instead of injecting botulism 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 nerves form at amputation sites and can cause severe, searing pain in limbs that no longer exist.
The study was conducted between 2022 and 2024 at two hospitals in western Ukraine, where an estimated 100,000 soldiers and civilians have lost limbs since the start of Russia’s full-scale invasion. About one-fifth of the participants received 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 botulism toxin-treated patients achieved substantial pain relief, defined as at least a 30% reduction. Only 43% of the comparison group reached this threshold. The injections appeared to work by calming nerve activity and reducing local inflammation around amputation sites.
Short term relief, long term questions
But the story changed in three months. Patients who received comprehensive care without botulinum toxin showed more lasting pain relief than those who received the injections. This is in line with previous research showing that the analgesic effects of botulinum toxin usually wear off after about three months.
Dr. Roman Smolynets, an anesthesiologist at the 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 towards helping amputees live with less pain and more dignity. But always as an add-on to integrated medical and surgical care, not as a monotherapy.”
Smolynets has treated thousands of war wounded 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 observer program, spending time at Cohen’s pain clinic and the Shirley Ryan AbilityLab.
The research team believes their targeted “perineural” approach could help with other types of nerve pain, including pain associated with shingles, carpal tunnel syndrome and pain after surgeries such as mastectomy. In the US, 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 chronic migraines. The two are also researching new 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 to future conflicts and suffered a traumatic brain injury while at the US Military Academy, this research has special personal meaning for me,” Cohen said.
Archive of Physical Medicine and Rehabilitation: 10.1016/j.apmr.2025.09.026
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