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Page 6 of 9 Burke et al. Plast Aesthet Res 2022;9:48 https://dx.doi.org/10.20517/2347-9264.2022.26

As a solution to these challenges, RPNIs have been used to provide sensory afferent signals for sensory
feedback from prosthetic devices [10,16,26] . Findings from a study on participants with upper limb amputations
[16]
revealed the ability of RPNIs to restore sensation . In this study, patients underwent the creation of RPNIs
on their median and ulnar nerves as well as implantation of indwelling bipolar electrodes in the RPNIs and
intact forearm muscles. After one month, patients participated in monthly experimental stimulation
sessions. Electrical stimulation of the RPNIs resulted in both meaningful and anatomically appropriate
proprioceptive and cutaneous sensations in the residual limb . These initial results are promising and
[16]
encourage further investigation into the potential of this interface to provide sensory feedback. The addition
of sensory feedback with efferent motor control would establish a robust bidirectional closed-loop
prosthetic paradigm that could significantly improve the quality of life for individuals with amputations and
would fully capture the potential of extremity prostheses [25,27] .

PREVENTION AND TREATMENT OF NEUROMAS AND POSTAMPUTATION PAIN
Debilitating chronic pain is common after limb amputation. An estimated fifty to eighty percent of patients
with limb loss suffer from residual limb pain (RLP) and phantom limb pain (PLP) [28,29] . These conditions are
associated with significant functional consequences, such as prosthetic abandonment and inadequate
prosthetic rehabilitation, as well as impairments in activities of daily living and decreased quality of life [29-32] .
It has been well established in the literature that successful treatment of symptomatic neuromas in this
patient population has the potential to alleviate both RLP and PLP [33-35] .

Symptomatic terminal neuromas develop when the transected axons of an injured nerve fail to reestablish
connections with their end organs, which are no longer present following amputation. Exuberant
regeneration of these axons occurs, forming disorganized, hyperexcitable, painful masses of Schwann cells,
axonal sprouts, blood vessels, and connective tissue [36,37] . Although multiple surgical interventions have been
proposed for symptomatic neuroma treatment, such as traction neurectomy, these conventional methods
have yielded unsatisfactory results including failed pain resolution and neuroma recurrence [38-40] .

The RPNI has been found to be an uncomplicated and effective solution for both the treatment and
prevention of symptomatic neuromas [17,33,41] . In contrast to other existing methods of neuroma treatment,
the RPNI addresses the regenerating nerve’s physiologic inclination for end organ reinnervation. In this
construct, the free autologous muscle graft undergoes revascularization and is reinnervated by regenerating
axons, forming new neuromuscular junctions. This leads to fewer axons without functional connections,
thereby decreasing the erratic axons that contribute to the formation of a painful neuroma [13,17] . Current
studies investigating whether or not neuromas form within the RPNI construct using ultrasound have not
shown neuroma formation within RPNIs.

Studies from our research group have shown that the utilization of RPNIs can successfully treat existing
symptomatic neuromas and phantom limb pain [33,42] , in addition to preventing the formation of neuromas
when prophylactically performed at the time of amputation . A retrospective study compared
[43]
postamputation pain outcomes between patients who underwent prophylactic RPNI surgery at the time of
amputation to age, gender, and level of amputation-matched control patients whose peripheral nerves were
instead treated with either traction neurectomy, suture ligature, burial of peripheral nerve within the nearby
muscle, or a combination of these strategies . RPNI patients experienced a significantly decreased
[43]
incidence of symptomatic neuromas (0% vs. 13.3%) and phantom limb pain (51.5% vs. 91.1%) after a mean
follow-up time of approximately one-year . Additionally, RPNI patients experienced an overall lower rate
[43]
of postoperative complications compared to the control group (31.1% vs. 55.6%), demonstrating that the
addition of RPNI surgery performed at the time of primary amputation does not increase surgical