American Society for Peripheral Nerve (ASPN)
Spring 2020
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What's new in nerve this month?
Theodore Kung, MD
Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain.
Carrie A. Kubiak MD, Stephen W.P. Kemp PhD, Paul S. Cederna MD, Theodore A. Kung MD
Plastic and Reconstructive Surgery. 2019; 144(3): 421-430e.
From the Department of Surgery, Section of Plastic and Reconstructive Surgery, and the Department of Biomedical Engineering, University of Michigan.

Q&A with ASPN member Theodore Kung, MD:
1. What is the take home message of your study?
Regenerative Peripheral Nerve Interfaces (RPNIs) are a novel way to leverage the biologic processes of nerve regeneration and muscle reinnervation to reduce the incidence of neuroma formation. In this manner, RPNIs can reduce the number of aimless axons within the residual limb after amputation and therefore mitigate the development of postamputation pain. Given the continued difficulty of numerous non-surgical and surgical options to reliably treat painful neuromas, the ability of RPNIs to physiologically treat and prevent neuroma formation leads to exciting opportunities to completely transform the landscape of both limb amputation and peripheral nerve surgery.

2. What are some of the challenges with regard to performing RPNIs at the time of major limb amputation to prevent neuroma pain?
Currently, our greatest challenge is widespread dissemination of the RPNI surgery technique to our colleagues outside of plastic surgery who also perform limb amputation. At our institution and others, we have worked hard to share the methods and mechanisms of RPNI surgery with orthopedic surgeons, vascular surgeons, and trauma surgeons. Moreover, we recognize that it is critical that each surgeon is performing RPNI surgery in a standardized fashion in order to optimize outcomes. As we continue to conduct clinical studies investigating the efficacy of RPNI surgery in the prevention of neuroma pain, future publications and presentations will serve to help accomplish these goals and to better define the role of RPNIs for all surgeons who perform amputation surgery.

3. Do you think that management of the nerves at the time of major limb amputation should become the new standard of care?
Yes unless clear contraindications exist, management of the peripheral nerves at the time of major limb amputation serves to decrease the propensity of painful neuroma formation. Importantly, our data also demonstrate a lower incidence of chronic phantom limb pain following prophylactic RPNI surgery. It is established that the longer patients experience pain, the more likely maladaptive feedback loops occur between the peripheral nervous system and the central nervous system. Therefore, our thinking is: Why allow painful neuromas to form in the first place after limb amputation? If the clinical situation is appropriate, why not try to reduce the experience of postamputation pain from the very beginning? RPNI surgery is already considered standard of care by plastic surgeons at the University of Michigan and it is quickly being adopted by surgeons of other specialties as well.

4. What are the next steps in your research?
We definitely have lot more work to do. Investigations are under way in the laboratory and clinical settings to help answer a number of important RPNI questions. For example, what is the optimal size of free muscle graft for a given caliber of peripheral nerve? What happens to sensory axons that regenerate into an RPNI? How many RPNIs should be performed during limb amputation? Can RPNI surgery reduce the amount of pain medications that patients take after amputation? We are excited to discover answers to these and other questions in the near future and look forward to sharing them with the ASPN community!

BACKGROUND: Postamputation pain affects a large number of individuals living with major limb loss. Regenerative peripheral nerve interfaces are constructs composed of a transected peripheral nerve implanted into an autologous free muscle graft. The authors have previously shown that regenerative peripheral nerve interfaces can be used to treat symptomatic end neuromas that develop after major limb amputation. In this study, they investigated the potential of prophylactic interfaces to prevent the formation of symptomatic neuromas and mitigate phantom limb pain.

METHODS: Patients who underwent limb amputation with and without prophylactic regenerative peripheral nerve interface implantation were identified. A retrospective review was performed to ascertain patient demographics, level of amputation, and postoperative complications. Documentation of symptomatic neuromas and phantom limb pain was noted.

RESULTS: Postoperative outcomes were evaluated in a total of 90 patients. Forty-five patients underwent interface implantation at the time of primary amputation, and 45 control patients underwent amputation without interfaces. Six control patients (13.3 percent) developed symptomatic neuromas in the postoperative period compared with zero (0.0 percent) in the prophylactic interface group (p = 0.026). Twenty-three interface patients (51.1 percent) reported phantom limb pain, compared with 41 control patients (91.1 percent; p < 0.0001).

CONCLUSIONS: Prophylactic regenerative peripheral nerve interfaces in major limb amputees resulted in a lower incidence of both symptomatic neuromas and phantom limb pain compared with control patients undergoing amputation without regenerative peripheral nerve interfaces, suggesting that prevention of peripheral neuromas following amputation may diminish the central pain mechanisms that lead to phantom limb pain.


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