Botox Injections Ease Phantom Limb Pain in Ukrainian War Amputees

Botulinum toxin injections – commonly known as Botox – provided greater short-term relief from phantom limb pain than standard medical and surgical care among Ukrainian war amputees, according to a new study led by Northwestern Medicine in collaboration with Ukrainian physicians.

The clinical trial, conducted between 2022 and 2024, enrolled 160 amputees treated at 2 hospitals in western Ukraine. The findings, published in Archives of Physical Medicine and Rehabilitation, could benefit millions of people with limb loss worldwide.

Pain is common amongst 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 live with limb loss, while in Ukraine, an estimated 100,000 soldiers and civilians have lost limbs since Russia’s full-scale invasion 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 senior study author Dr. Steven Cohen, 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,” added co-author Dr. Roman Smolynets, anesthesiologist and intensive care specialist at the 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,” Smolynets added.

Botox injections ease phantom limb pain

Participants were treated at the First Medical Union of Lviv and Ivano-Frankivsk Regional Hospital. Roughly one-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, medications and other interventions.

Pain levels were assessed at baseline and after one and three months post-treatment, focusing on both phantom limb pain (in the missing limb) and residual limb pain (at the stump site).

After one month:

• The botulinum toxin group reported an average 4-point reduction in phantom limb pain on a 10-point scale
• The standard care group improved by only one point
• 69% of patients receiving botulinum toxin achieved meaningful pain reduction (≥30% decrease), compared with 43% in the control group.

By three months, however, the effects of botulinum toxin had diminished, and patients receiving comprehensive care reported more sustained relief – consistent with prior research showing that the toxin’s effects typically last about three months.

A novel 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 novel, ultrasound-guided approach to inject the toxin directly around painful nerve endings and surrounding soft tissues, rather than into muscles or skin.

This targeted “peri-neuromal” method may explain the strong short-term pain reduction observed, as it helps quiet nerve activity and reduce local inflammation.

Previous studies have shown botulinum toxin’s potential for treating neuropathic pain, but none have injected it around painful nerves. The findings suggest that this approach could also help alleviate other forms of nerve pain, such as shingles-related pain, carpal tunnel syndrome or post-surgical pain following procedures like mastectomy or thoracotomy.

However, Cohen and colleagues stress the need for larger, randomized trials to confirm their findings, refine patient selection and optimize botulinum toxin dosing.

Future research should also explore whether repeat injections over time could produce sustained 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. Peri-neuromal botulinum toxin injection for war-related postamputation pain: A pragmatic, multicenter, comparative-effectiveness study. Arch Phys Med Rehabil. 2025. doi: 10.1016/j.apmr.2025.09.026

This article is a rework of a press release issued by Northwestern University. Material has been edited for length and content.