Targeted Muscle Reinnervation for Pain Management in Amputee Patients

Ron Sanchez had his foot crushed during a logging accident as a teenager and lived in extreme pain for over 20 years. After developing an infection in his foot, Ron needed a below the knee amputation – but continued to feel pain in his leg even after it was gone.

Known as phantom limb pain, Ron described it “like sticking your leg in a bucket of water that’s being electrified,” he told WVU Medicine.

Desperate for relief, his medical provider suggested targeted muscle reinnervation, which would allow the nerves of Ron’s amputated leg to be transferred into new muscles at the amputation site.

For Ron, this surgery was life changing. He was able to go from constant, severe pain to hardly any at all, and was able to utilize a prosthetic limb and increase his mobility for the first time ever.

But how?

In 2002, Dr. Gregory Dumanian and Dr. Todd Kuiken at Northwestern Memorial Hospital developed targeted muscle reinnervation to allow upper extremity amputee patients to have better and more varied control of their myoelectric prosthesis by transferring nerve that had been used in the residual limb to a local, functionless muscle. By doing so, these once functionless muscles, or target muscles, can amplify the signal, which can then be picked up by sensors placed on the skin.

In essence, an amputee patient could stimulate action, and potentially move, their prosthetic limb just by thinking about it.

But in addition to a lack of range of motion, nearly 80% of amputee patients in the U.S. suffer from chronic pain. Targeted muscle reinnervation, however, can potentially change that.

Phantom Limb Pain

A large percentage of amputees report experiencing phantom limb pain, which is thought to occur due to interactions between painful neuromas and the central nervous system, creating cortical reorganization. The Limb Loss Research and Statistics Program studied 1,538 patients with amputations of either an upper- or lower-limb or bilateral amputation of upper or lower limbs and found that 79% reported phantom limb pain.

A 2019 study by Dumanian et al., published in the Annals of Surgery, examined 28 major-limb amputees with chronic pain who had not received prior treatment for pain. Enrolled in a surgical trial at Northwestern and Walter Reed National Military Center, patients were randomly given either targeted muscle reinnervation or a standard neuroma surgery to help relieve their pain.

Using a numerical rating scale of 0 to 10 to report the change in pre- and post-operative pain, the study found that there was an average decrease in phantom limb pain of 3.2 for the targeted muscle reinnervation patients, while there was an average increase in phantom limb pain of 0.2 for the standard care surgery patients one-year post-surgery.

What’s more, 72% of targeted muscle reinnervation patients reported either no or mild symptoms of phantom limb pain at their respective longest follow-ups, which ranged from six to over 24 months post-surgery. Meanwhile only 40% of the standard care patients reported the same results.

Neutralizing Amputees’ Neuroma Pain

Neuromas can be especially painful for amputee patients because part of the nerve itself is removed during the amputation, which leaves the nerve unable to repair itself. Up to 60% of nerve injury patients can develop neuromas.

A 2014 study, to which Dr. Dumanian and Dr. Kuiken contributed, titled “Targeted Muscle Reinnervation: A Novel Approach to Postamputation Neuroma Pain,” examined 15 patients who had undergone targeted muscle reinnervation and had experienced neuroma pain prior to their procedure.

Researchers noted that 14 out of the 15 patients reported complete resolution of pain after receiving targeted muscle reinnervation, and the remaining patient experienced significant improvements in pain, though it was not completely eliminated.

While studies comparing surgical outcomes for symptomatic neuromas is lacking, one meta-analysis reviewed 54 studies and found that surgical treatment was effective in 77% of patients, noting there was no significant differences between the various surgical techniques.

Relieving Residual Limb Pain

Also known as “stump pain,” residual limb pain resides in the remaining part of the limb post-amputation and occurs in an estimated 76% of amputee patients. A 2020 study by Mioton, Dumanian et al., published in Clinical Orthopaedics and Related Research, examined 33 patients who received targeted muscle reinnervation for treatment of a symptomatic neuroma. One-year post-surgery, their scores for residual limb pain dropped from an initial average of 6.4 prior to surgery to 3.6.

Additionally, while 58% of participants reported severe residual limb pain (with scores of 7 to 10) prior to the operation, that number dropped to 6% after the surgery.

Using a Patient-reported Outcome Measurement System, in which higher scores indicate worse outcomes, it was found the average residual limb pain intensity scores dropped from 53.4 to 44.4, while the average residual limb pain interference scores (the extent to which pain interferes with a patient’s daily activities) dropped from 60.4 to 51.7 pre- and one-year post-operation, respectively.

What’s Next for Targeted Muscle Reinnervation?

Recent advancements in surgical techniques have allowed for the use of targeted muscle reinnervation in combination with the creation of a regenerative peripheral nerve interface (RPNI) for patients in need of a transradial amputation who have preoperative limbs that have a viable pronator quadratus.

This technique can be used for myoelectric thumb opposition and the prevention of neuromas and associated pain, according to a 2021 Healio Orthopedics article. Researchers hope to be able to use implantable myoelectric sensors in the future, which, when used in RPNI muscle grafts, could allow for additional prosthetic signals.

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