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Toyoda et al. Plast Aesthet Res 2022;9:17 https://dx.doi.org/10.20517/2347-9264.2021.118 Page 5 of 17

[24]
evidence supporting their effectiveness, no definitive conclusion could be drawn . There has also been
active research in neuromodulation techniques. A recent systematic review and meta-analysis of nine
randomized controlled trials and five quasi-experimental studies found some hopeful data in transcranial
direct current stimulation, although no definitive conclusions were reached yet given the infancy of these
techniques for amputees .
[25]
Multiple disciplines continue to tackle the difficult challenge of post-amputation pain with some exciting
preliminary results. However, clinical results of these nonsurgical options continue to be suboptimal, as
evidenced by these numerous, diverse, and inconclusive studies. Perioperative management, including
assessment of patient and injury risk factors, preoperative consultation of the acute pain service,
preoperative loading of neuropathic pain medication, intraoperative blocks, perineural catheter infusion,
ketamine infusion, and numerous non-FDA approved postoperative pain management have been proposed,
albeit with no conclusive results .
[14]

Surgical treatment of post-amputation pain
Surgical interventions for symptomatic neuromas can be categorized as either active/reconstructive or
[26]
passive/ablative . Active/reconstructive measures include TMR and RPNI, which will be discussed in
further detail below. Both of these procedures provide the problematic nerve “somewhere to go and
[27]
something to do”, thereby diverting its natural regenerative processes away from neuroma formation .

Passive/ablative procedures include excision of the symptomatic neuroma, burying the problematic nerve in
other tissues after neuroma excision, centro-central neurorrhaphy, relocation nerve grafting, nerve capping,
and traction neurectomy [26,28-30] .

Simple neuroma excision has not been demonstrated to have good long-term efficacy. In a study of patients
with upper extremity symptomatic neuromas who underwent surgical treatment by Guse et al. , 47% of
[31]
those who underwent simple neuroma excision required reoperation. Domeshek et al. used neuroma
[32]
excision with proximal transposition in 70 upper and lower extremity neuroma patients and found
improved self-reported pain, depression, and quality of life scores. This was corroborated in a more recent
meta-analysis by the Washington University group of similar methods, which found that excision with
transposition or neurolysis with coverage resulted in a longer reduction in symptomatic neuroma pain
[33]
compared to other methods, including simple excision .
Centro-central neurorrhaphy refers to fascicular dissection and coaptation of the terminal nerve ending
with a hollow tube or nerve graft construct [26,29] . Souza et al. showed that in the foot and ankle, excision of
[34]
nerve segments causing symptomatic neuroma pain and bridging the gap with nerve allograft resulted in
improved pain behavior and pain interference scores on PROMIS.

Relocation nerve grafting refers to the use of nerve allograft on the terminal nerve and redirection away
from the painful area. Economides et al. demonstrated effective prophylactic reduction in phantom
[35]
symptoms, neuroma formation, and improved ambulation rates after coaptation of the tibial and common
peroneal nerve, which was then wrapped with collagen. In another study by Prantl et al. , in fifteen lower
[36]
limb amputation patients, the sciatic nerve was split longitudinally, and the two ends were coapted to each
other via the epineurium. These patients experienced reduced pain intensity scores as well as a decreased
duration of pain attacks .
[36]