In a groundbreaking study conducted amidst the ongoing conflict in Ukraine, researchers from Northwestern Medicine in collaboration with Ukrainian medical professionals have revealed that botulinum toxin injections offer significantly enhanced short-term relief from phantom limb pain compared to standard medical and surgical treatments. This discovery comes as a beacon of hope for the thousands of war amputees struggling with debilitating post-amputation pain, a condition that severely hampers mobility and quality of life globally.
Phantom limb pain, characterized by painful sensations perceived in the absent limb, is a complex neuropathic condition afflicting the majority of amputees. The prevalence and severity of this pain often undermine the successful use of prosthetics and dramatically diminish patients’ day-to-day function and psychological well-being. The urgency of improved pain management strategies is underscored by staggering statistics: over two million Americans live with limb loss, while in Ukraine, an estimated 100,000 soldiers and civilians have lost limbs since the conflict intensified in 2022.
This multicenter pragmatic study recruited 160 amputees from two major hospitals in western Ukraine — the First Medical Union of Lviv and Ivano-Frankivsk Regional Hospital — treating them between 2022 and 2024. Participants were divided into two cohorts: one group received standard comprehensive care, encompassing surgical revision, nerve blocks, physical and psychological therapy, and medications, while the other underwent additional peri-neuromal injections of botulinum toxin targeted specifically at painful nerve endings, known as neuromas.
What sets this study apart is its innovative injection methodology. Unlike conventional botulinum toxin applications that primarily target muscles for cosmetic or spasticity treatments, researchers employed ultrasound-guided injections to deliver the toxin intricately around the painful nerve endings and surrounding soft tissues adjacent to neuromas. This peri-neuromal approach significantly heightened the precision of the treatment, potentially quelling nerve hyperactivity and local inflammatory processes which are key drivers of chronic neuropathic pain.
At the one-month post-treatment mark, patients who received the botulinum toxin injections reported an average reduction of four points on a 10-point phantom limb pain scale, a stark contrast to the mere one-point improvement observed in the control group. Moreover, nearly 69% of the injection group experienced clinically meaningful pain relief—defined as a pain reduction exceeding 30%—compared to only 43% among those receiving standard care. These results underscore the potent analgesic impact of localized botulinum toxin delivery in the acute phase following treatment.
However, the study also illuminated the temporal limitations of this approach. By the three-month follow-up, the botulinum toxin group’s analgesic benefits began to wane, a pattern consistent with the known pharmacodynamics of botulinum toxin, whose neuromodulatory effects typically persist for approximately three months. Contrarily, patients undergoing comprehensive medical and surgical interventions exhibited more durable pain relief, highlighting the necessity of integrating botulinum toxin as an adjunct rather than a standalone therapy.
Dr. Steven P. Cohen, a professor of anesthesiology and vice chair of research and pain medicine at Northwestern University Feinberg School of Medicine, and a retired U.S. Army colonel, spearheaded this study. Leveraging his military medical expertise, Cohen traveled to Ukraine to initiate the collaborative research effort. Dr. Roman Smolynets, an anesthesiologist and intensive care specialist at the Multidisciplinary Clinical Hospital of Emergency and Intensive Care in Lviv, played a pivotal role on the Ukrainian side, providing invaluable insight into frontline trauma care during wartime conditions.
The collaboration between Cohen and Smolynets exemplifies the profound synergy between military medicine and civilian healthcare, particularly in conflict zones where innovative pain management strategies can profoundly affect patient outcomes. Their shared commitment aims not only to alleviate suffering but also to restore function and dignity for war-injured individuals facing the daunting challenges of limb loss.
Beyond its immediate clinical implications, this study opens new avenues for expanding the therapeutic use of botulinum toxin injection techniques. The targeted peri-neuromal injection model could be extrapolated to treat diverse neuropathic pain disorders, including postherpetic neuralgia, carpal tunnel syndrome, and pain following extensive surgical procedures such as mastectomy or thoracotomy, conditions that similarly involve aberrant nerve signaling and local inflammation.
This modality represents a paradigm shift by focusing treatment directly at the locus of nerve irritation and pain generation rather than general muscle or skin tissue. Such precision medicine approaches could ultimately refine pain management protocols and minimize systemic medication burdens and their attendant side effects.
Importantly, the study’s findings also emphasize the necessity for future research efforts. Larger, randomized controlled trials are critical to validate these initial promising results, optimize dosing regimens, and identify patient subpopulations most likely to benefit. Moreover, investigations into the efficacy of repeated botulinum toxin administration could illuminate strategies for sustaining long-term pain control, drawing parallels from chronic migraine treatment protocols where periodic injections maintain symptom remission.
The research team also recognizes the psychosocial dimensions of post-amputation pain and the value of multidisciplinary care, integrating surgical, pharmacologic, physical, and psychological therapies to comprehensively address this multifaceted condition. Botulinum toxin injections, when added judiciously to such a framework, enhance the therapeutic armamentarium available to clinicians managing complex neuropathic pain syndromes.
Dr. Cohen’s personal connection to military medicine—informed by his service and his son’s current infantry role—adds a heartfelt dimension to this work. The compassionate drive behind this research transcends academia, embodying a tangible commitment to improving lives affected by the ravages of war, both in Ukraine and globally.
As the study’s promising results prepare for publication in the esteemed journal Archives of Physical Medicine and Rehabilitation, the international medical community eagerly anticipates its impact on clinical practice. The collaboration between Northwestern University, Ukrainian hospitals, and military medicine stands as a testament to the power of global partnerships in addressing pressing health challenges through innovative science.
In parallel, ongoing research efforts by Cohen, Smolynets, and colleagues continue to explore novel interventions for war-related injuries, including traumatic brain injury and post-traumatic stress disorder, at premier institutions such as Walter Reed National Military Medical Center and Northwestern University. This multifaceted approach underscores the necessity of holistic strategies to support recovery and rehabilitation for those affected by armed conflicts.
Ultimately, this study marks a pivotal advance in the quest to alleviate phantom limb pain, elevating botulinum toxin injections from cosmetic or traditional uses into the realm of precision neuropathic pain management for war amputees. The hope is that such innovations will extend beyond Ukraine’s battlefields, transforming pain care and improving quality of life for amputees worldwide.
Subject of Research: Treatment of post-amputation phantom limb pain using peri-neuromal botulinum toxin injections.
Article Title: Peri-Neuromal Botulinum Toxin Injection for War-Related Postamputation Pain: A Pragmatic, Multicenter, Comparative-Effectiveness Study
News Publication Date: 21-Oct-2025
Web References: http://dx.doi.org/10.1016/j.apmr.2025.09.026
Image Credits: Northwestern University
Keywords: Amputation, Pain, War
