New Approaches to Conquering Phantom Limb Pain and Restoring Sensation

Phantom limb pain (PLP) and painful neuromas impact a high percentage of people with amputations and significantly compromise their social and emotional well-being. It is often not the amputation that causes the greatest disability, but the associated chronic pain, which significantly reduces the quality of life for those who experience it. 1 Despite advances in pain treatment, post-amputation pain remains one of the most challenging pain conditions to treat, with many patients reporting only limited success with traditional treatments. 2 This motivated a microvascular plastic surgeon in Italy, Alexander Gardetto, MD, to implement a new strategy for pain management. Targeted sensory reinnervation (TSR) is a surgical technique that offers hope for alleviating PLP and improving patient outcomes. A unique outcome of this procedure is not only the complete, or almost complete, elimination of pain, but also a pathway to sensory restoration. The Prevalence and Impact of Post-amputation Pain On average, each year over 500,000 Americans experience limb loss or are born with a limb difference. 3 Limb loss often results in phantom limb sensation, residual limb pain, or PLP. Studies have shown that 95 percent of individuals experience at least one of these three sensations after amputation, with PLP being most common, affecting nearly 80 percent. 1 Phantom limb sensation is a feeling that the nonexistent limb is still present and most commonly felt as a strong, momentary pins and needles sensation, as well as an intermittent disagreeable twisting, pulling, or burning sensation. 4 While residual limb pain originates from the remaining part of the amputated limb, PLP is characterized by pain that feels to be emanating from the missing limb, despite its absence. PLP and residual limb pain can severely impact an individual’s daily life, contributing to physical and emotional distress. 2 Complexity and the Need for Effective Treatment Post-amputation pain is a multifactorial combination of peripheral, spinal, and supraspinal mechanisms. 2 A key factor in the development of PLP is the loss of sensory feedback from the missing limb. This lack of information triggers the brain to generate spontaneous signals. These signals, which lack a meaningful origin, are perceived as pain by the central nervous system, leading to the experience of PLP. 5 Understanding these mechanisms is crucial for developing targeted, evidence-based treatment plans. Currently there is no universally accepted gold standard for treating PLP, and management typically involves a combination of occupational and physical therapy, pharmacotherapy, psychological interventions, and in some cases, surgical treatment. 1 Occupational and physical therapy approaches to PLP include a variety of desensitization techniques, mirror therapy, graded motor imagery, massage, and transcutaneous electric nerve stimulation. Pharmacological approaches include the use of opioids, N-methyl-D-aspartate (NMDA) receptor antagonists, anticonvulsants, calcitonin, antidepressants, and local anesthesia. While these treatments may provide some relief, they often fall short in providing long-term pain management. 6 Surgical interventions such as nerve stimulation and spinal cord stimulation target specific pain mechanisms, but again results can be inconsistent. 2 In recent years, there has been growing interest in reconstructive surgical options and approaches. Because loss of information from the missing limb is a key factor in the development of PLP, recreating a pathway for such information, and therefore “reinstalling” the limb with the brain, might be a central and causal step in treatment. A pathway can be created surgically by the rearrangement of motor and sensory nerves. One such technique, targeted muscle reinnervation (TMR) has shown promise by rerouting severed nerve endings to nearby expendable motor nerve branches in the residual limb. The control of a myoelectric prosthesis is improved by increasing the number of independent muscle signals. Interestingly, patients undergoing TMR have reported sensations in areas where the nerves were redirected, suggesting the potential for an innovative approach: TSR. 5 The Promise of TSR TSR emerges as a potentially transformative technique for treating PLP and restoring sensation after amputation to address the lack of sensory feedback from the missing limb. TSR works by redirecting the nerves that would normally control the amputated limb to a dedicated area of skin on the residual limb. By surgically reactivating nerves in these specific areas, TSR may provide the brain with afferent signals that replace the missing limb within the sensory pathways of the brain. This process holds promise for recreating authentic sensation from a missing limb and may lead to a significant enhancement of the individual’s quality of life. 5 Upper-limb TSR Outcomes Over the past three years, Gardetto has observed the outcomes from TSR surgery in a cohort of seven upper-limb patients. In interviews, conducted by the lead author of this article, these patients were asked to describe their pre-surgery experience with PLP. One patient described it as “unbearable and excruciating,” and 10/10 pain that required two trips to the emergency room where the only way to treat her pain was with IV pain medications. She had no social interactions except with her family. Another patient described her experience: “At times I wanted to have an amputation to a higher level because it seemed to only get worse, especially at work and under stress. The pain was with me all the time. The doctors kept giving me medication in increasing dosages, but it did not help.” One patient remarked, “The pain medication worked for maybe ten to 30 minutes, then it returned, even worse.” After undergoing TSR, each of these individuals reported a dramatic improvement in being completely, or almost completely, pain-free. One described her experience: “My life changed in that I don’t have pain anymore, and for sure I worry less because I do not take any medication. That was the thing that made me worry the most, taking pain-killing medication.” Another said, “I wake up in the morning now and I have no pain, with or without my prosthesis. I am much more relaxed.” Every individual interviewed said they would undergo the surgery again and would strongly recommend it to others. [caption id="attachment_262961" align="alignright" width="800"] Left image: The residual nerves of the hand after amputation were redirected in the forearm residual limb below the elbow using the new technique of TSR and TMR to enable reinnervation and improve function. Right image: A phantom limb map on the forearm residual limb shows how the brain perceives all five fingers following nerve reinnervation. Gardetto A, Müller-Putz GR, Eberlin KR, Bassetto F, Atkins DJ, Turri M, Peternell G, Neuper O, Ernst J. Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface. J Clin Med. 2025 Jan 10;14(2):417. doi: 10.3390/jcm14020417. PMID: 39860422; PMCID: PMC11765609.)[/caption] Sensory Mapping and Feedback Integration In addition to the significant reduction in pain, another outcome of TSR surgery was the restoration of sensation. The earliest signs of sensation began to return a few weeks after surgery. One woman, who is a prosthesis wearer, said, “I feel more secure, and it feels like I still have my hand because I can feel it on the inside, and I can feel it moving. It feels like I have my hand because I can feel all of it, the palm too, not only the fingers. There are many sensations that I have: heat, cold, and even tickling.” For this woman, a sense of embodiment was established. All individuals who underwent TSR were able to draw a map of their phantom hands on their forearms within five to six months of the surgery. They were all able to create a map of the phantom limb on the skin that accurately represented the position of each of their fingers and palms on the reinnervated area. Sensory testing of warm and cool temperatures was identified and discriminated on the tips of each finger they had drawn. The results for TSR surgery strongly suggest that the procedure is an effective treatment alleviating PLP and restoring a pathway to explore sensory feedback in individuals who have lost a limb. Notably, TSR is a minimally invasive surgery, enabling it to be a promising option for future patients who have severe neuromas or PLP. TSR can also be an option to prevent the formation of painful neuromas as an elective procedure performed at the time of an amputation. The next logical step for individuals with upper-limb amputations and advanced prosthetic technology is to provide sensory feedback mechanisms incorporated within a prosthetic hand. Enabling an individual to truly feel what they are touching has the potential to significantly enhance the functionality of a prosthesis, and create a more intuitive, integrated experience. This sense of embodiment may also have a positive impact on acceptance of the prosthesis and wear compliance. As one patient said, “Psychologically, the prosthesis is mine now, and with that also an instrument of psychological force for me.” [caption id="attachment_262962" align="alignright" width="348"] Components of the Suralis feedback system, including the sensor cover that detects ground contact of the prosthetic foot. Photographs courtesy of Saphenus Medical Technology.[/caption] Lower-limb Options for PLP, Proprioception, and Gait Stability As with individuals with upper-limb amputations, the TSR procedure also results in a phantom limb map on individuals’ residual lower limbs. This has opened the door for sensory feedback to be applied on this innervated skin. To realize its full potential, this newly created sensory area needs to be stimulated. Neuropsychologist Herta Flor, PhD, states that the restoration of sensitivity creates embodiment and thus acceptance of the exoprosthesis and has been described as a fundamental option for the treatment and reduction of PLP. 6 In addition to surgical options, research has investigated various noninvasive feedback methods for prosthetic limbs using haptic signals (e.g., vibrations, electrical stimulation) transmitted to the residual limb to deliver information about the prosthetic limb (e.g., position, time of contact) to its wearer. Suralis, developed by Saphenus Medical Technology, is the first medical device registered by the US Food and Drug Administration that provides sensory feedback in lower-limb prostheses not only under laboratory conditions but also in everyday life for those affected. The product can be used with any lower-limb prosthesis regardless of the amputation level. A sensor cover, which is pulled over the prosthetic foot, detects the rolling movement on the sole of the prosthetic foot from the heel to the toes and sends this sensory information to the body in real time via vibration elements. Various options are available for the attachment of the vibration motors depending upon the amputation level. These include a cuff attached on the thigh, which these vibrotactile elements are sewed into, or a silicone pad that is inserted into the socket. Each sensor is connected to a vibration element and transmits ground contact information. When a sensor is triggered, one motor vibrates and transmits the information to the skin, where the vibration is felt by the user. Through this feedback loop, users can feel their natural gait cycle. The users feel the progression of the heel to the toes touching the ground, and in turn, this enables them to take the next step. [caption id="attachment_262963" align="alignright" width="243"] The Suralis feedback system in use during daily activities such as cycling.[/caption] Benefits of Using Sensory Feedback for Lower-limb Prostheses The sensory afferent information that occurs in the first phases of gait (initial contact and loading response), when the heel strikes the ground, triggers multiple reflex reactions and complex regulatory mechanisms in the human body and brain. 7 If these sensory stimuli are absent or reduced, as is the case when walking with a prosthesis, the person has no, or incorrect, information about available ground contact. This results in great uncertainty, as users do not know at what point they can safely transfer their body weight to their supporting leg. Possible compensation mechanisms are increased force on heel strike to better perceive the moment of initial contact, or the knee is locked in extension to maintain stability. Even with only minor sensory impairment, the gait will become slow and cautious. 8 At the very beginning when using Suralis/sensory feedback, users learn to consciously perform the rolling movement from the heel to the big toe and receive vibration signals at different points on the cuff for the rolling points at the back of the heel and the front of the big toe. This conscious provocation of triggering the actuators is the first step toward walking more naturally and symmetrically. The proprioceptive information of the sole of the foot is fundamental for all balance-maintaining reactions. 9 Over time, users gain confidence in accepting the prosthesis more as part of their bodies. This means that situations that are otherwise tricky for prosthesis wearers, such as climbing stairs, walking in the dark, or walking backward, can be mastered more easily. After ten to 14 days or around 20,000 steps, the vibration as such is no longer perceived by users. Instead, embodiment effects emerge, such as feeling in the leg or the prosthesis feeling warm like the biological foot. This is usually the point at which the pain situation improves in patients where PLP was present. The sensory feedback system can then be seen as a kind of sensory bypass that bridges the artificial prosthetic foot and is virtually integrated into the body. Motor training leads to an increase in cortical representations. The theory of representations in the brain goes back to the Canadian neurophysiologist Donald Hebb, PhD. In 1949, he presented a model of how the storage of learned material could take place in the brain. According to Hebb’s theory, there is a representation for every memory content. Hebb postulated that the representation is formed via the strength of the synapses. If certain neurons become active together, for example when practicing a movement, the transmission between these neurons would become increasingly easier. 10 [caption id="attachment_262965" align="alignright" width="297"] The use of sensory feedback allows the prosthesis user to perform balance training. Photograph courtesy of Janine Ortmann.[/caption] Hebb’s theory states, “What fires together wires together.” According to this principle, all neurons that are active at the same moment are combined into one representation. Synchronized discharge also leads to improved memory storage. The sustained increase in synapse strength is referred to as long-term potentiation. Learning is the change in synaptic connections triggered by activity. This means that an event-correlated stimulus is necessary to achieve the expected effects. 11 Providing sensory feedback to users enables them to distinguish between different surfaces and to sense obstacles on the ground. Ongoing feedback improves gait stability and safety by reducing the risk of falling. Prosthetic leg users reported that they can walk faster and walk longer distances when using Suralis. Previous research suggests that the loss of sensory feedback leads to increased cognitive load. The provision of sensory feedback reduces cognitive load and enables the utilization of the prosthesis to be less fatiguing when compared to having no feedback from the missing limb. 12 Additionally, users who experienced significant pain when walking with a prosthesis reported a significant reduction in PLP when wearing Suralis. Ongoing feedback, consistent with the natural movements of the human body, is interpreted by the brain as feedback from the missing limb. This allows the brain to reestablish neural connections that were lost during the amputation. Suralis can be used both by patients after TSR to stimulate the phantom limb map as well as by patients who have not undergone surgery. Experience of Lower-limb Feedback One woman reported that using sensory feedback changed the way she walks. With the feedback, she now knows where the ground is without looking at it. It allows her to take more gentle steps and therefore walk with less noise. Previously, she had to press her heel down extremely hard on the floor to hear the impact of her foot to know the location of her foot by hearing the sound. The feedback also now enables her to do exercises with a balance board. [caption id="attachment_262964" align="alignright" width="388"] The use of sensory feedback allows the prosthesis user to perform balance training and ADLs, such as walking the dog. Photograph courtesy of Waltraud Marx.[/caption] In addition to improving gait performance and reducing PLP, sensory feedback also had a significant effect on prosthesis embodiment and how the users perceived their prostheses. One user said, “My prosthesis makes me feel it is a part of me. It now feels warm, as if it was a part of my body.” Interestingly, the impact of using sensory feedback is also noticeable for people with congenital limb absence. One prosthesis user, who was born without a leg, mentioned that in addition to the skin sensations, he benefitted from the auditory signals. When standing, he describes that he enjoys the vibrations because he can feel the shift in weight and focus more intently on what he is doing. As illustrated in these examples, the application of sensory feedback to lower-limb prostheses appears to demonstrate a significant benefit to individuals by improving gait stability, overall safety, a reduction of PLP, and an enhancement in their sense of embodiment . In conclusion, TSR and a novel lower-limb sensory device offer new approaches for individuals with upper- and lower-limb loss, especially those who have experienced significant PLP. Diane J. Atkins, OTR/L, FISPO, is an assistant clinical professor, Department of Physical Medicine and Rehabilitation, Baylor College of Medicine. Ruth Leskovar, PhD, is a clinical researcher, Saphenus Medical Technology. Mag. Rainer Schultheis is the CEO and cofounder of Saphenus Medical Technology. Muriel Kofler is a medical student at the University of Innsbruck. Alexander Gardetto, MD, is adjunct professor of Plastic, Reconstructive and Aesthetic Surgery, University Hospital of Padova; medical director, Brixsana Private Clinic; and clinical director, Saphenus Medical Technology. References Ephraim PL, Wegener ST, MacKenzie EJ, Dillingham TR, Pezzin LE. Phantom Pain, Residual Limb Pain, and Back Pain in Amputees: Results of a National Survey. Archives of Physical Medicine and Rehabilitation. 2005/10/01;86(10). Hsu E, Cohen SP. Postamputation pain: epidemiology, mechanisms, and treatment | JPR. Journal of Pain Research. 2013/02/13;6. Caruso M, Harrington S.(2024). Prevalence of Limb Loss and Limb Difference in the United States: Implications for Public Policy {White Paper}. Amputee Coalition Shenaq, S et al, (1989) The Painful Residual Limb: Treatment Strategies. In DJ Atkins & RH Meier (Eds) Comprehensive management of the Upper Limb Amputee. Springer Verlag, New York. Gardetto A, Müller-Putz GR, Eberlin KR, Bassetto F, Atkins DJ, Turri M, Peternell G, Neuper O, Ernst J. Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface. J Clin Med. 2025 Jan 10;14(2):417. doi: 10.3390/jcm14020417. PMID: 39860422; PMCID: PMC11765609. Flor H. The modification of cortical reorganization and chronic pain by sensory feedback. Appl Psychophysiol Biofeedback. 2002 Sep;27(3):215-27. Perry J. Gait Analysis-Normal and pathological function. Slack, 1992. Beck F. Sport macht schlau. Goldegg Verlag 2014. Kauffman T, Nashner L, Allison L. Balance is a Critical Parameter. Orthopedic Rehabilitation. Orthopaedic Physical Therapy Clinics in North America. 1997; 6(1), 43 - 79. Hebb, D. O. (1949). The Organization of Behavior: A Neuropsychological Theory. New York: Wiley and Sons. Götz-Neumann K. Gehen verstehen: Ganganalyse in der Physiotherapie. Thieme, 4th edition, 2016. Gonzalez, J., Suzuki, H., Natsumi, N., Sekine, M., & Yu, W. (2012). Auditory display as a prosthetic hand sensory feedback for reaching and grasping tasks. 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1789–1792.

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