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Eftekari et al. Plast Aesthet Res 2022;9:43 https://dx.doi.org/10.20517/2347-9264.2022.33 Page 11 of 13

the standard of care for decades, but this approach fails to address the underlying regenerative changes of a
transected nerve that lead to the creation of a symptomatic neuroma. Hiding the residual nerve deep within
the muscle may provide additional shielding but will inevitably lead to the production of a future neuroma,
which is likely why 20%-30% of symptomatic neuromas are refractory to this approach and reoperation
rates are as high as 65% .
[17]
The TMR approach was the first alternative treatment modality to this traditional approach and was
originally developed as the first transcutaneous myoelectric neural interface to communicate with a
[20]
prosthetic . Through efforts to improve prosthetic control, TMR inadvertently addressed the underlying
physiology that leads to symptomatic neuroma formation . This has been clinically shown to reduce
[37]
phantom limb pain and rates of opioid use in amputation patients and is now used routinely during
amputation procedures as prophylaxis to prevent future neuroma formation [12,20] . However, this approach is
limited by the location of the anastomosis site and the number of skeletal muscles that are denervated from
their motor neurons for coaptation of the transected nerve. Moreover, the TMR approach sacrifices some of
the traditional shielding benefits that come from burying a nerve into muscle or bone, which may lead to a
future recurrence of a symptomatic neuroma.

Similar to TMR, the RPNI approach was also conceived as a means to improve and fine-tune neuro-
prosthetic control . Providing a skeletal muscle target for the severed nerve inadvertently led to significant
[31]
decreases in symptomatic neuroma pain and phantom limb pain, enjoying the same benefits of TMR by
[28]
addressing the underlying regenerative physiology . The RPNI approach excels compared to the TMR
approach in that multiple muscle grafts can be used for multiple nerves, and larger nerves can be split
among multiple grafts for better size-matching . Since the RPNI approach does not require transecting
[27]
healthy pure motor nerves, there is no limit to the number of muscle grafts that can be used for this
approach . Additionally, RPNI provides enhanced flexibility in choosing targets and does not rely on the
[18]
potential limitation of viable motor nerve targets. However, due to the lack of direct blood supply to the
muscle grafts, the RPNI approach is limited by the size of the individual grafts and can potentially lead to
[27]
avascular necrosis of the grafts if they are crafted too large .
The IO approach with medullary transposition offers the transected nerve a secluded and privileged
environment compared to the muscle-based approaches. The medullary canal also provides an environment
[38]
that is highly vascular and contains stem cells, providing an optimal environment for a transected nerve .
The highly shielded medullary cavity provides a safe environment far from the surface of the skin and any
moving muscle, while the ONI provides a target to harness the underlying physiology of a regenerating
nerve. Moreover, the larger space within the medulla allows for more complex and bidirectional electrodes
that can be securely fastened to the cortical bone, which may allow future prosthetics with more selectivity
and a higher-fidelity signal [18,33] . However, the IO with ONI approach has yet to be tested in a large animal
model, and thus conclusions regarding the usefulness of this as a neural interface in humans must be
guarded .
[36]
CONCLUSION
This review serves as a benchmark for assessing the current common treatment modalities of symptomatic
neuromas and highlights the differences among each approach. Although the standard of care for neuroma
treatment has remained stable over the past few decades, developments in the world of neuro-prosthetics
have extended our understanding of peripheral nerve injury and repair and have provided alternative
treatment avenues that take advantage of the underlying physiology of a regenerating nerve. The
cornerstones of symptomatic neuroma resection include providing a regenerating nerve with a secluded and