Botulinum toxin injections – commonly known as Botox – provided greater short-term relief of phantom limb pain from standard medical and surgical care among Ukrainian war amputees, according to a new study by Northwestern Medicine in collaboration with Ukrainian doctors.
The clinical trial, conducted between 2022 and 2024, involved 160 amputees treated at 2 hospitals in western Ukraine. The findings, published in Archives of Physical Medicine and Rehabilitationcould benefit millions of people with limb loss worldwide.
Pain is common among amputees
Post-amputation pain affects most amputees, severely limiting prosthetic use, mobility and overall quality of life. In the US, more than 2 million people are living with limb loss, while in Ukraine, an estimated 100,000 soldiers and civilians have lost limbs since Russia’s widespread invasion in 2022.
“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,” said the study’s senior author. Dr. Steven Cohenprofessor of anesthesiology and vice president for research and pain medicine at Northwestern University Feinberg School of Medicine.
“Our results suggest that botulinum toxin could potentially be a powerful short-term tool for the treatment of post-amputation pain when used alongside comprehensive medical and surgical care,” added co-author Dr. Roman Smolinetsanesthesiologist and intensive care specialist at the Multidisciplinary Emergency and Intensive Care Hospital in Lviv, Ukraine.
“It could be another step towards helping amputees live with less pain and more dignity. But always as an additional point to integrated medical and surgical care, not as a monotherapy,” Smolynets added.
Botox injections relieve phantom limb pain
Participants were treated at the First Medical Union of Lviv and the Ivano-Frankivsk Regional Hospital. About a fifth of patients received botulinum toxin injections around painful nerve endings (neuromas) in addition to standard care. The remainder underwent comprehensive medical and surgical treatment, including nerve blocks, surgical revision, physical therapy, psychological therapy, medication, and other interventions.
Pain levels were assessed at baseline and at one and three months post-treatment, focusing on both phantom limb pain (the missing limb) and residual limb pain (at the site of the stump).
After one month:
- The botulinum toxin group reported an average reduction of 4 points in limb pain on a 10-point scale
- The standard care group improved by only one point
- 69% of patients treated with botulism toxin achieved a significant reduction in pain (≥30% reduction), compared to 43% in the control group.
By three months, however, the botulinum toxin’s effects had diminished, and patients who received comprehensive care reported more prolonged relief — consistent with previous research showing that the toxin’s effects typically last about three months.
A new injection technique
While botulinum toxin is best known for its cosmetic use, it is also an established treatment for chronic pain due to its ability to block nerve signals.
In this study, researchers used a new, ultrasound-guided approach to inject the toxin directly around painful nerve endings and surrounding soft tissue, rather than into muscle or skin.
This targeted “perineural” method may explain the pronounced short-term pain reduction seen, as it helps calm nerve activity and reduce local inflammation.
Previous studies have shown the potential of botulinum toxin to treat neuropathic pain, but none have injected it around painful nerves. The findings suggest that this approach could also help relieve other forms of nerve pain, such as pain associated with shingles, carpal tunnel syndrome, or postoperative pain after procedures such as mastectomy or thoracotomy.
However, Cohen and colleagues stress the need for larger, randomized trials to confirm their findings, improve patient selection, and optimize botulinum toxin dosing.
Future research should also investigate whether repeated injections over time could produce consistent benefits for post-amputation pain, as they appear to do for migraine treatment.
Reference: Segin N, Smolynets R, Barroso J, Molinets N, Pasquina PF, Cohen SP. Perineural botulinum toxin injection for pain after war-related amputation: A pragmatic, multicenter comparative effectiveness study. Arch Phys Med Rehabil. 2025. doi: 10.1016/j.apmr.2025.09.026
This article is a repeat of a press release issued by Northwestern University. Material has been edited for length and content.
