Botulinum toxin injections have shown greater short-term relief for phantom limb pain in Ukrainian war amputees compared to standard care, according to a new study led by Northwestern Medicine in collaboration with Ukrainian physicians. The research, published in the Archives of Physical Medicine and Rehabilitation on October 21, involved 160 amputees treated at two hospitals in western Ukraine between 2022 and 2024.
Post-amputation pain is a common issue that limits prosthetic use and mobility, affecting quality of life for amputees. In the United States, more than 2 million people live with limb loss, while in Ukraine, it is estimated that over 100,000 soldiers and civilians have lost limbs since the Russian invasion began in 2022.
“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,” said Dr. Steven P. Cohen, senior study author, professor of anesthesiology and vice chair of research and pain medicine at Northwestern University Feinberg School of Medicine.
“Our results show that botulinum toxin potentially could be a powerful short-term tool for treating post-amputation pain when used alongside comprehensive medical and surgical care,” said Dr. Roman Smolynets, co-author and anesthesiologist at Multidisciplinary Clinical Hospital of Emergency and Intensive Care in Lviv, Ukraine.
“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.”
Participants in the study were treated at the First Medical Union of Lviv or Ivano-Frankivsk Regional Hospital. About 20% received botulinum toxin injections near painful nerve endings, while the rest received standard medical and surgical care, including surgical revision, nerve blocks, physical and psychological therapy, medications, and other procedures.
Pain levels were measured at the start, one month, and three months after treatment. At one month, those who received botulinum toxin reported an average reduction of four points in phantom limb pain on a 10-point scale, compared to a one-point reduction in the standard care group. Additionally, 69% of patients in the botulinum toxin group achieved at least a 30% drop in pain, versus 43% in the other group.
However, by three months, the effects of botulinum toxin had diminished, and patients receiving comprehensive care showed more lasting pain relief. This aligns with previous findings that the pain-relieving effects of botulinum toxin typically last about three months.
The study used a novel injection method: ultrasound guidance allowed for precise delivery of botulinum toxin around painful nerve endings and soft tissues. This targeted approach may explain the strong short-term pain reduction observed. Previous studies have demonstrated botulinum toxin’s effectiveness for neuropathic pain, but not with this specific injection technique.
The researchers suggest that this method could also be useful for other types of nerve pain, such as that caused by shingles, carpal tunnel syndrome, or surgeries like mastectomy.
Dr. Cohen traveled to Ukraine in 2024 to help launch the study and worked closely with Dr. Smolynets and Dr. Nadiya Segin, who is advancing the use of botulinum toxin and nerve stimulation for war injuries. Smolynets will visit Chicago for an observership program to collaborate further with Cohen.
The team emphasizes the need for larger trials to confirm these findings and to determine if repeated injections could provide longer-lasting relief for post-amputation pain, similar to their use in migraine treatment. Cohen and Smolynets are also conducting additional studies on treatments for traumatic brain injury and PTSD in Ukraine and at 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.
The study received partial funding from the U.S. Department of Defense and the ASPEN Medical Foundation.